Abstract. Synthesis and Application of Functional Branched Macromolecules â from Site Isolation and Energy Harvesting to Catalysis. By. Stefan Hecht. Doctor of ...
Synthesis and Application of Functional Branched Macromolecules – from Site Isolation and Energy Harvesting to Catalysis By Stefan Hecht Diplom (Humboldt Universität) 1997
A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Chemistry in the GRADUATE DIVISION of the UNIVERSITY of CALIFORNIA at BERKELEY
Committee in charge: Professor Jean M. J. Fréchet Professor Jonathan A. Ellman Professor Ronald Gronsky
Fall 2001
The dissertation of Stefan Hecht is approved:
University of California, Berkeley Fall 2001
Synthesis and Application of Functional Branched Macromolecules – from Site Isolation and Energy Harvesting to Catalysis Copyright 2001 By Stefan Hecht
Abstract
Synthesis and Application of Functional Branched Macromolecules – from Site Isolation and Energy Harvesting to Catalysis By Stefan Hecht
Doctor of Philosophy in Chemistry University of California, Berkeley Professor Jean M. J. Fréchet, Chair
The symbiosis of our understanding of structure property relationships in many biological macromolecules and our increased ability to prepare large synthetic macromolecules with exquisite structural precision has generated a new area of research where chemistry and materials science join with biology. For example, numerous biological systems utilize the concept of site isolation whereby an active center or catalytic site is encapsulated, frequently within a protein, to afford properties that would not be encountered in the bulk state. The ability of a dendritic shell to encapsulate functional core moieties and to create specific site-isolated nanoenvironments, thereby affecting molecular properties, not only mimics natural systems but affords novel materials with unique characteristics. Furthermore, introduction of donor chromophores at periphery of dendrimers having a central acceptor dye enables spatial and spectral energy concentration at the core. Continuing the effort towards designing bio-inspired
1
macromolecules, this dissertation describes the use of different polymer architectures to encapsulate active sites that have either photophysical, photochemical, or catalytic functions and the evaluation of site isolation using a variety of different techniques. While the first part is mainly concerned with different synthetic approaches towards site isolation of porphyrin moieties, the second part describes the design of light-driven catalytic systems incorporating both light harvesting and energy conversion. The fundamental knowledge that can be gleaned from such investigations has implications that range from the preliminary design of artificial enzymes to the construction of molecular-scale devices. After an overview of dendritically encapsulated functions (Chapter 1) and a brief account of a novel synthetic approach to benzene core dendrimers (Chapter 2), site isolation of porphyrin moieties within dendrimers, their linear structural isomers, and branched star polymers is described in Chapters 3, 4, and 5. Among the key findings of these chapters are: the important role of core size and structure for encapsulation, the superior ability of the dendrimer backbone to serve as an insulating shell and energy harvesting building block, as well as the practical and versatile use of dendritic initiators to generate functional star polymers with a high degree of site isolation. Following a short description of hyperbranched porphyrin architectures having multiple active sites (Chapter 6), the encapsulation of benzophenone-based singlet oxygen sensitizers at the core of a regular dendritic micelle is described in Chapter 7. The utilized amphiphilic design leads to the first example of light-driven catalysis within dendrimers. In the context of light-harvesting dendrimers, this finding represents the unique opportunity to convert the excitation energy that is funneled to the core into chemical energy, thereby
2
truly mimicking natural photosynthesis. The design of first systems capable of combining light harvesting and excited state catalysis is outlined in Chapter 8. Finally, Chapter 9 illustrates an alternative, more practical approach towards light-harvesting photocatalytic polymers involving the use of monolithic materials.
approved:
3
To Anne and Sophia
It is only with the heart that one can see rightly; what is essential is invisible to the eye.
Antoine de Saint-Exupéry
Table of Contents Acknowledgment .......................................................................................................
v
Chapter 1: Overview of Dendritic Encapsulation of Function ..................................
1
Introduction ........................................................................................
2
Design Concepts, Synthetic Approaches, and Experimental Tools ...
4
Photoresponsive Systems ...................................................................
7
Catalytically Active Systems .............................................................
17
Conclusion .........................................................................................
24
References ..........................................................................................
25
Chapter 2: An Alternative Synthetic Approach to Dendritic Macromolecules Utilizing an Alkyne Cyclotrimerization Reaction ...................................
33
Introduction ........................................................................................
34
Results and Discussion ......................................................................
36
Synthesis ......................................................................................
36
Characterization ...........................................................................
40
Synthetic Scope and Limitations .................................................
44
Conclusion .........................................................................................
47
Experimental ......................................................................................
47
References ..........................................................................................
63
Chapter 3: Site Isolation in Porphyrin Core Dendrimers – The Effect of Core Size and Structure ....................................................................................
67
Introduction ........................................................................................
68
Results and Discussion ......................................................................
69
i
Synthesis ......................................................................................
69
Absorption and Emission Properties ............................................
73
Fluorescence Depolarization and Hydrodynamic Properties .......
76
Conclusion .........................................................................................
81
Experimental ......................................................................................
82
References ..........................................................................................
90
Chapter 4: Site Isolation in Porphyrin Core Dendrimers and their Isomeric Linear Analogs – The Effect of Polymer Architecture........................................
94
Introduction ........................................................................................
95
Results and Discussion.......................................................................
96
Synthesis and Characterization ....................................................
96
Absorption/Emission Properties and Energy Transfer Studies ....
101
Conclusion..........................................................................................
108
Experimental ......................................................................................
108
References...........................................................................................
113
Chapter 5: Encapsulation of Functional Moieties within Branched Star Polymers...
117
Introduction ........................................................................................
118
Results and Discussion ......................................................................
119
Synthesis ......................................................................................
119
Fluorescence Quenching Experiments .........................................
128
FRET Studies ...............................................................................
129
PGSE NMR Experiments.............................................................
135
Solvatochromic Probes.................................................................
139
ii
Conclusion..........................................................................................
141
Experimental ......................................................................................
142
References ..........................................................................................
156
Chapter 6: Hyperbranched Porphyrins – a Rapid Synthetic Approach to Multiporphyrin Architectures ..................................................................
163
Introduction ........................................................................................
164
Results and Discussion ......................................................................
166
Synthesis ......................................................................................
166
Polymer Characterization.............................................................
170
Conclusion .........................................................................................
173
Experimental ......................................................................................
174
References ..........................................................................................
178
Chapter 7: Light-driven Catalysis within Dendrimers – Designing Amphiphilic Singlet Oxygen Sensitizers ......................................................................
180
Introduction ........................................................................................
181
Results and Discussion ......................................................................
183
Synthesis ......................................................................................
183
Characterization ...........................................................................
186
Catalysis .......................................................................................
187
Conclusion .........................................................................................
189
Experimental ......................................................................................
189
References ..........................................................................................
198
iii
Chapter 8: Light-harvesting and Conversion – Towards the Next Generation Photocatalysts...........................................................................................
202
Introduction ........................................................................................
203
Results and Discussion ......................................................................
205
Core Design .................................................................................
205
Internally Labeled Dendritic Building Blocks .............................
209
Donor Chromophores……….......................................….……...
213
Conclusion .........................................................................................
214
Experimental ......................................................................................
215
References ..........................................................................................
228
Chapter 9: Exploring Alternative Polymer Architectures – Towards Photocatalytic Monoliths .................................................................................................
232
Introduction ........................................................................................
233
Results and Discussion ......................................................................
234
Conclusion .........................................................................................
238
Experimental ......................................................................................
238
References ..........................................................................................
242
iv
Acknowledgment It is my greatest pleasure to express my gratitude to the large number of people who have been influential and supportive over the course of my studies and my life in general. Here, I am attempting to thank the remarkable individuals who made this journey a marvelous and memorable experience. First and foremost, my Ph.D. supervisor Professor Jean M. J. Fréchet: Your encouragement, advice, and extremely generous support have been a wonderful companion throughout my graduate career. It has been my privilege and pleasure to enjoy your extraordinary mentorship. It is my honor to acknowledge some of the people who created such positive atmosphere around the lab, in particular the legendary “Team 709”. Dr. Adam Freeman: Your humorous nature and big smile have entertained me delicately so many times. Dr. Alex Adronov: Your critical opinion and help are highly valued. Furthermore, the next generation and especially Will Dichtel: It has been my great pleasure to work with you and witness your positive attitude and enthusiasm for chemistry. Good luck to all of you in the future. Special thanks to John Klopp who has been a great friend with a good heart. Also, I would like to thank Alex “Trigger” Trimble and Jennifer Tripp for their help as well as Dr. Henrik Ihre and Dr. Todd Emrick for excellent collaborations and for simply being extremely nice guys. Last but not least, I would like to acknowledge some other outstanding individuals who made my stay in the Fréchet group a pleasant one: Dr. Nikolay Vladimirov, Dr. Barney Grubbs, Dr. Eric Peters, Dr. Patrick Malenfant, Dr. David Tully, Dr. Nicolas “Nico” Bensel, Dr. Hanting Chang, Dr. Caiguo Gong, Dr. Dario
v
Pasini, and Dr. Maria Vicent as well as many of the current group members. I hope we all cross paths again in the future. In addition to my former and current labmates, I would like to acknowledge Dr. Craig Hawker and Dr. Eva Harth of the IBM Almaden Research Center for a stimulating collaboration. Thanks also to Professor De Schryver and his group. Last but not least, I am deeply indebted to some dedicated and passionate individuals who sparked my initial interest in science and inspired me tremendously: Albrecht Vetter, Dr. Jürgen Bendig, and Professor William G. Dauben. The interaction with all of you has greatly influenced me and will not be forgotten. Personally, I would like to thank my parents and in particular my mother for her great courage and endless love that will always be in my heart. Also, I would like to acknowledge my terrific grandmother and the entire family for their help and encouragement. In addition, I am indebted to the parents of my fiancée for supporting our relationship and welcoming me in their family. Most importantly, I am grateful to Anne, my love, and our daughter Sophia Maria. What would life be without you? Thank you for sharing your lives with me. With deepest love and affection I dedicate this work to you.
vi
Chapter 1:
Overview of Dendritic Encapsulation of Function
Abstract The ability of the dendritic shell to encapsulate functional core moieties and to create specific site-isolated nanoenvironments, thereby affecting molecular properties, has been explored. Utilizing the distinct properties of the dendrimer architecture, active sites that have either photophysical, photochemical, or catalytic function have been placed at the core. The natural design principle of site isolation contributes to bridging the gap between biology and materials science and its application to problems in materials research is likely to prove extremely fruitful in the long term, with short-term applications in the construction of improved optoelectronic devices for example. This chapter has been reproduced in part with permission from Angew. Chem. Int. Ed. 2001, 40, 74-91. Copyright 2001 Wiley-VCH.
1
Introduction The field of dendrimer chemistry1 has undergone a very rapid development evolving from discovery and the establishment of synthetic approaches to the characterization of dendrimer properties and the design of functional dendrimers.2 The dendritic scaffold may therefore be used for the spatial arrangement of functionalities and the tailoring of properties via the interplay of the structural subunits. Dendrimers truly represent unique artificial building blocks as a result of the fine control over both their size and their molecular architecture, and therefore their three-dimensional nanoscale structure (Figure 1.1).3
Figure 1.1. Space-filling representation of a fourth generation poly(benzyl ether) zinc porphyrin core dendrimer (top) and Cytochrome P450 (bottom), illustrating their comparable dimensions.
Significant progress has been made in the use of dendritic frameworks to surround active core molecules. This involves exploiting the inherent topological features of a 2
dendrimer in which a core is surrounded by a branched shell that carries external “surface” groups. Dendritic shielding actually amounts to an encapsulation that can create a distinct microenvironment around the core moiety, therefore affecting its properties. This effect may result from the synergistic combination of the intrinsic chemistry of the building blocks of the dendrimer and the reduced accessibility of its core. The encapsulation motif draws its inspiration from our increasing understanding of molecular biology. Enzymes provide an impressive demonstration of the profound effect a protein shell has on the active site of the enzyme. For example, the remarkable CH bond activation performed by the heme protein Cytochrome P4504 and the long range electron transfer processes mediated by other Cytochromes5 would not be possible with unprotected hemes.6 In many cases, Nature appears to create functional diversity by changing the architecture around the active entity rather than by direct chemical modification of that entity. For instance, in a light harvesting antenna complex of photosynthetic bacteria, the bacteriochlorophyll molecules exist as two distinct chromophore subunits that have different absorption characteristics as a consequence of their spatial arrangement.7 Working mostly with small molecules, chemists traditionally synthesize new molecules8 to tailor properties.9 However, the challenge of mimicking Nature by applying the design principle of property variation via architectural modification continues to fascinate.
3
Design Concepts, Synthetic Approaches, and Experimental Tools The astonishing structural diversity of natural systems such as enzymes is achieved by a combination of different amino acid building blocks and a variety of interactions leading to macroscopic organization. Seemingly complex folding processes give rise to the secondary and tertiary structure. Further interactions between the individual subunits can lead to even higher order quaternary structures, impressively demonstrated in “molecular machines” such as ATP synthetase. The globular structure of proteins is primarily based on the hydrophobic effect that exposes hydrophilic residues to the surrounding medium while sequestering hydrophobic fragments in the interior. Specific interactions such as hydrogen bonding occurring at the active site contribute to stabilization of the transition states thereby favoring certain reaction pathways. Without the benefit of evolution, dendrimers already provide unadorned steric protection and a unique – though still unsophisticated - “inner” environment that reflects the nature of its building blocks. The geometric encapsulation of a core moiety by dendritic wedges ideally gives rise to a sphere or ovoid with a radius determined by the size of the core, and also the size and number of dendrons surrounding it (Figure 1.2). It is important to note that the steric crowding between the dendritic segments induces the shape of the molecule. This is itself strongly dependent on the flexibility of the dendritic building block, the branching pattern, the size (or generation number) of the dendrons, as well as the interactions of the dendrons and the chain ends, not only with each other but also with the surrounding medium. In addition, the degree of encapsulation of the core is a function of its size and the specific directional orientation of the dendrons. 4
Figure 1.2. Attachment of multiple dendrons to polyfunctional cores gives rise to spherically shaped dendrimers. An idealized fully extended conformation is shown, in which the terminal group are not mixed with the inner building blocks or the core.
Some of the most common core functionalities are shown in Figure 1.3 and vary greatly in size from compact metal ion complexes to large buckyballs or even porphyrins. N N
N
N N
M
N
N
N
III
III
Fe L, Mn L
Fe
N
N
Fe
N
N
N
II
IV
N
II
M = H2, Zn , Si
Fe
II
II
M = Ru , Os
S Fe
S
N M
II
M = H2, Zn , Fe ,
S
N
M
N II
N
N
M N
N
N
N
N
O
Fe
O
S
III
O M O III
II
M = Fe , Ru O O
O N
O
N Cu
L
L
III
M = Er , Eu , Tb
N N
O N
Figure 1.3. Examples of core functionalities commonly exploited in spherical encapsulation.
While both convergent and divergent strategies1 may be used to achieve encapsulation, the convergent strategy appears to be more versatile as it avoids multiple 5
synthetic operations on the often-exotic core and leads to more precise and uniform material.2b Within the last few years, elegant synthetic protocols have been developed that form the core moiety directly from dendritic precursors in the final step of the sequence.10 This direct method usually facilitates chromatographic purification owing to a more pronounced difference in elution behavior of substrates vs. products, whereas the more conventional process of grafting dendrons onto a polyfunctional core benefits from higher yields and added synthetic flexibility. For example, porphyrin core dendrimers have been prepared by Fréchet and coworkers comparing chemical modification of a preformed core with direct core-forming condensation.11 An analogous study by Schlüter and coworkers12 explored the preparation of “cylindrical” dendrimers13 by the direct synthesis or core modification approaches. Due to the inherent perfect dendritic coverage, this direct approach is superior to the dendron grafting route and it has since been further improved.14 In addition to the often complicated and time-consuming preparation and isolation of the compounds, the choice of experimental technique used to ascertain the effect of the dendritic shell is crucial and depends mainly on the core functionality. A variety of experimental tools have been employed to study the shape of the molecule in solution and to quantify the shielding of the core moiety. Changes in the microenvironment of core dyes are conveniently analyzed by absorption and emission techniques that rely on the stabilizing or destabilizing effect of the local medium on the electronic states of the chromophore. Parameters such as medium polarity (from spectral shifts)15 or viscosity (from fluorescence anisotropy decays),16 can be deduced from such measurements. Classic Stern-Volmer type experiments have also been used extensively. Herein, the 6
bimolecular deactivation of the excited state caused by penetration of an external quencher molecule through the dendritic shell allows for an evaluation of the accessibility of the core.17 Other kinetic methods that do not involve a fluorescence signal, include cyclic voltammetry (CV)18 as well as chemical reactions performed within the dendrimer itself. In CV measurements, the occurrence of reversible or irreversible electron transfer and the change in redox potential provide information about the isolation of the core moiety; whereas in kinetic studies, rates, chemical yields, and selectivity studies give insight into substrate diffusion and binding to the reactive or catalytic site. A vast number of physical tools are available to complement the above mentioned techniques, for instance NMR relaxation experiments can be used in connection with paramagnetic cores19 or with conventional proton relaxation.20 Furthermore, alternative techniques dealing with dendrimer conformation and dynamics, such as gel permeation chromatography (GPC), differential viscometry, or computational methods are available.1c
Photoresponsive Systems The environment of a chromophore is able to affect its photophysical properties such as absorption and emission characteristics as well as its photochemical behavior. We have already mentioned Nature’s perfection in creating such environments and even spatially arrange multiple chromophores with respect to each other to further enhance performance in a synergistic fashion. In a first simple approach to study the effect of the microenvironment on the properties of an encapsulated dye, Hawker, Wooley and Fréchet attached solvatochromic probes to the core or focal point of dendrimers.15a Analysis of 7
the UV/vis absorption spectra of a series of Fréchet-type dendrons with a p-nitroaniline solvatochromic probe attached to their focal point (Figure 1.4) showed a pronounced bathochromic shift of the absorption maxima in non-polar solvents such as CCl4 or toluene with increasing generation. The most dramatic change occurred between generations 3 and 4 presumably as a consequence of the transition from an extended to a more globular structure that better encapsulates the core. Correlation with Taft's solvent polarizability parameter21 π* indicated that, at high generation, the local environment near the chromophore resembles that of highly polar solvents such as DMF.
Figure 1.4. Dendritic p-nitroanilines as solvatochromic probes. The space-filling model illustrates increasing encapsulation of the focal chromophore by the dendrimer backbone in higher generations (G-1: top left, G-4: bottom left, G-6: right).15a
In subsequent work, Moore and coworkers utilized the emission of phenylacetylene dendrimers modified with an electron donor at the focal point to probe the local environment.15b An anomalous spectral shift in the fluorescence maximum of the charge transfer state was observed in higher generations. Corroborating the earlier 8
findings of Hawker et al.,15a an abrupt change was observed between the fourth and fifth generations suggesting the occurrence of dendritic encapsulation. Even more recently, Smith and Müller studied Newkome-type dendrimers having a tryptophan core and correlated the observed spectral shifts to the ability of the solvent to form hydrogen bonds and therefore stabilize the emitting state.15c Porphyrin core dendrimers have enjoyed considerable interest for their potential in catalysis as well as artificial photosynthesis, and have been studied extensively in the Aida, Diederich, and Fréchet laboratories. In their initial publication,22 Aida and coworkers observed that the fluorescence of a fourth generation dendrimer was quenched more efficiently that that of a smaller first generation dendrimer by a small molecule quencher such as Vitamin K3. However, the opposite effect was observed when a larger molecule such as a first generation free base dendritic porphyrin was used as the quencher. These results led to the conclusion that, in higher generation dendrimers, the dendrons act as a trap for small molecules for which they have an affinity, but cooperatively serve as a barrier for larger ones. Later, investigations performed by our group23 using a similar series of dendrimers and benzyl viologen as the quencher showed a comparable increase in quenching efficiency at higher generation. By introducing peripheral anionic groups leading to pre-complexation of the cationic methyl viologen quencher, Sadamoto et al. were able to observe an electron transfer reaction through the dendrimer backbone.24 Consequently, efficient fluorescence quenching in self-assembled ensembles of free base porphyrins and zinc porphyrins having oppositely charged peripheral groups was reported.25 In an alternative and very elegant approach to demonstrate the accessibility of the core as well as the influence of the size of the 9
penetrating molecule, Aida and coworkers examined the interaction of dendritic imidazoles with zinc porphyrin cored dendrimers (Figure 1.5).20a Evaluation of the measured binding constants showed that dendritic interpenetration is greatly diminished at higher generations of both the zinc porphyrin and the ligand.
Figure 1.5. Ligation of dendrimers with zinc porphyrin cores by dendritic imidazoles. The interaction of a low generation complex and ligand gives rise to a high binding constant (left), whereas the interaction of a high generation complex and ligand leads to a small binding constant (right).20a
Further insight into the role of the dendritic shell as a barrier for external quenching agents, therefore increasing the lifetime of the excited state, was provided by the groups of Balzani and Vögtle, who investigated tris(bypyridine)ruthenium core dendrimers.26,27 In aerated solution, the higher generation Newkome-type poly(ether amide) dendrimers (Figure 1.6) exhibited increased quantum yields of emission as well as enhanced excited state lifetimes due to the shielding effect of the dendritic shell, which limits the quenching by molecular oxygen.26a The reduced quenching efficiency of molecular oxygen can be attributed to its lower solubility in the dendritic interior, a 10
possibly decreased diffusion rate, and/or better core solvation. More recently, the authors found a similar trend with related poly(benzyl ether) dendrimers.26b These studies enable a comparison of the effect of the different dendrimer backbones, i.e. Newkome-type and Fréchet-type. In aerated acetonitrile solution at room temperature, the second generation Newkome-type compound exhibits about twice the excited state lifetime and a 30 nm redshifted emission compared to the third generation Fréchet-type compound. Obviously, the more polar poly(ether amide) dendrons stabilize the MLCT excited state more efficiently than the less polar poly(benzyl ether) dendrons.
Figure 1.6. An increase in the emission quantum yield and excited state lifetime in dendrimers with a tris(bipyridine)ruthenium core is attributed to diminished quenching by molecular oxygen.26
One of the major aims for the introduction of bulky dendrons around a central moiety has been to prevent self-aggregation of dye molecules in the solid state. This self11
aggregation is mainly caused by π-π stacking interactions. Isolation of the individual chromophores greatly enhances their optical properties due to reduced self-quenching. Unfortunately, as the size of the core dye increases, larger or higher generation dendrons have to be used to achieve efficient shielding.16b To overcome this problem, McKeown and coworkers took advantage of the coordination sphere of a silicon phthalocyanine to attach Fréchet-type dendrons in the axial position.28a,29 The third generation compounds having an axial dendritic substitution showed a significant decrease in exciton coupling in the solid state due to efficient separation of the chromophores, while the equatorial analogs exhibited strong aggregation. In a key report, Kawa and Fréchet demonstrated the use of self-assembled dendritic carboxylate ligands to encapsulate lanthanide ions thereby greatly improving their luminescence properties.30 Assembly of three anionic dendrons around erbium(III), europium(III), or terbium(III) ions (Figure 1.7) led to an enhancement of luminescence efficiency with increasing generation due to site isolation of the lumophores, drastically reducing its rate of self-quenching. In the context of fiber optics applications, the match of the 980 nm excitation with the typically used pumping wavelength makes the erbium(III) cored dendrimers and their conceptual analogs interesting candidates for glass fiber amplifiers. In addition, the authors observed an antenna effect resulting in efficient sensitization of core luminescence by the dendritic ligands. Interestingly, the energy transfer was dramatically reduced in an isomeric complex having a 1,2,5-branching pattern instead of the more common 1,3,5-substitution at the focal point. Clearly, the focal aromatic structure plays a crucial role for the observed antenna effect.
12
Figure 1.7. The assembly of three dendritic wedges having focal carboxylate functionalities around a lanthanide ion leads to site isolation and greatly enhanced luminescence properties.30 The core has been moved to the front for better visibility.
Recently, Jiang and Aida thoroughly studied similar morphology effects on the antenna effect in a series of free base porphyrins substituted with varying numbers of high generation dendrons (Figure 1.8).20c Excitation energy migration was found to be extremely efficient in the fully labeled porphyrins, indicating complete encapsulation and cooperativity of the dendritic subunits in the spherical morphology.
Figure 1.8. Increasing the number of dendritic substituents leads to more efficient encapsulation of the porphyrin core. Energy transfer from the dendrimer backbone to the core is greatly enhanced in the spherical morphology.20c
13
An impressive demonstration of the effect of morphology on energy transfer was provided by the same authors investigating the IR-accelerated cis-trans isomerization of an azobenzene core moiety (Figure 1.9).20b Achieving full encapsulation by using either fourth or fifth generation dendrimers, they noted that the rate of isomerization was two orders of magnitude faster under controlled IR irradiation than was the case for a purely thermal reaction. This phenomenon was reported to occur only when a particular IR stretching frequency of the aromatic branching units (1597 cm-1) was employed for irradiation. Given the activation barrier for the cis-trans isomerization (21.4 kcal mol-1), the authors concluded that this process involved approximately five low energy IRphotons (1597 cm-1 ≈ 4.6 kcal mol-1).
Figure 1.9. The harvesting of multiple IR photons by a fifth generation poly(benzyl ether) dendrimer with an azobenzene core leads to an acceleration of the cis-trans isomerization.20b
14
Junge and McGrath investigated somewhat similar molecules and the effect of large dendrons on the rate of thermal cis-trans reversion of photo-isomerizable units.31,32 Not unexpectedly, given the large degree of conformational freedom that prevailed in the investigated poly(benzyl ether)-type dendrimers, the small disturbance created by isomerization at the core is quickly dissipated through the bulky but flexible shell. In addition to steric protection, a dendrimer molecule is uniquely suited to arrange multiple peripheral functional groups around a single core unit. By introducing an energy transfer interaction or similar electronic “communication” between the periphery and the core, the design of dendritic light-harvesting antennae becomes feasible.33 In such systems, an array of terminal donor chromophores may collect many photons and transfer their energy to the core acceptor unit, which can also be excited independently of the periphery. Since emission is observed from the core only, the system serves as a spatial and spectral energy concentrator or “molecular lens” (Figure 1.10).
Figure 1.10. Illustration of a dendritic light-harvesting antenna.33 The absorption of light of a broad spectral range by peripheral chromophores leads to an enhanced emission from the core as a result of efficient energy transfer.
15
Essentially, this mimics the primary events in photosynthesis, where the lightharvesting complex funnels its excitation energy to the special pair leading to subsequent charge separation. Two types of systems, which either use the dendritic architecture solely as a scaffold,34 or involve the dendrimer backbone in the energy transfer event,20b,c,29c,30,35 have been explored. Our group has recently shown that an amplification of the core acceptor emission can be achieved in high generation dendrons labeled with multiple peripheral donor chromophores.34a-c The amplification effect has its origin in the enhanced donor absorption cross-section and the extremely fast rate of through space energy transfer to the core, therefore giving rise to efficient light harvesting.34b Another key finding was reported by Moore and coworkers, who demonstrated a significant acceleration of energy transfer within dendrimers having an internal energy gradient, which was due to a stepwise decrease of the HOMO-LUMO gaps of the branching units when progressing toward the acceptor.35b Balzani and coworkers constructed bipyridinebased polynuclear metal complexes and were able to control the direction of energy transfer via alteration of the excited state energies by introducing appropriate metals.35e This strategy impressively demonstrates how supramolecular chemistry can be used to assemble multiple chromophores and furthermore control their relative orientation. From a more applied perspective, dendritic scaffolds have been used to spatially arrange the different components necessary for the construction of organic light emitting diodes. The good film properties obtained from spin casting combined with the formation of a single layer only (having either one or multiple components) offer the potential advantage of very economic device fabrication. Moore and coworkers have described devices based on phenylacetylene dendrimers having a luminescent anthracene core and 16
peripheral tertiary aromatic amines.36 In their dendrimers, the triaryl amines served as the hole transporting element, where as the phenylacetylene dendrons acted as electron transporters. Since the dendrimer backbone was shown to be capable of efficient energy transfer,35a,b charge recombination within the dendrimer led to a directed transduction of excitation energy to the emitting core. Although a good correlation was found between the photoluminescence and the electroluminescence spectra, the devices had a very low efficiency due to self-quenching caused by solid-state aggregation. In a related system based on stilbene dendrimers,37 the device efficiency was found to increase by nearly an order of magnitude as the generation number increased from 1 to 2, again demonstrating the value of the site isolation concept. More recently, Freeman et al. have prepared naphthyl diphenyl amine terminated poly(benzyl ether) dendrimers having coumarin or pentathiophene cores.38 Two component single layer devices consisting of the dendrimer serving as both hole transporter and emitter, as well as an oxadiazole derivative acting as the external electron transporter were fabricated and good matching of photoluminescence and electroluminescence was observed. The modular design of this approach and the partial site isolation of the central dye by the dendritic framework allows for a combination of dendrimers having differently emitting cores thus affording a color tunable system.
Catalytically Active Systems The size of a dendrimer is roughly comparable to that of many enzymes and, just like enzymes, dendrimers are able to create a microenvironment around a reactive site. While Nature has had an ample opportunity to optimize enzymes through evolutionary 17
processes, one of our best tools for the optimization of dendrimers is mimicry, even if based on grossly simplified models. Therefore, significant advances have been made in the last years and more sophisticated dendritic molecules that perform more and more catalytic operations will continue to appear. Already, numerous reports have outlined approaches to the use of dendrimers as molecular-scale chemical reactors. Ideally, the dendritic superstructure would provide a tool to tune and enhance the activity and selectivity of a single encapsulated active site.39,40 Among the most attractive targets is the mimicry of natural oxidation catalysts, in particular heme-based oxygenases.41 Manganese porphyrins carrying oxidatively robust poly(phenylester) dendrons were reported by Moore and coworkers42 and found to catalyze the shape-selective43 epoxidation of alkenes using iodosobenzene as the oxidizing agent (Figure 1.11). In both intra- and intermolecular competition studies, the second generation dendrimer-based catalyst was up to four times more selective towards less hindered terminal double bonds than a simple manganese tetraphenylporphyrin used for comparison purposes. Due to their efficient shielding, the dendritic catalysts showed excellent oxidative stability. More recently, Kimura et al. have published their first results employing cobalt phthalocyanine core dendrimers to catalyze the oxidative transformation of thiols to disulfides using molecular oxygen as the oxidant.29d The authors found that the catalytic activity of the second generation catalyst dropped by 20% when compared to that of the first generation, suggesting no significant restriction of substrate penetration. Not surprisingly, the larger, higher generation catalyst displayed enhanced stability as a result of its better encapsulation by the dendritic shell.
18
O O
O
O
O O
O O O
O
O
O O
O
O
O
O
O
O
O
O O O
O O O
O
O
O
O
O
O
O
O
O
O
O O
O O
O
O
N O N Mn
O
O
O
O O O
O
O O O
O
O O
O
O O
O
O
O
O
O O
N
N
O
O O
O
O
O
O O
O O
O
O O
O
O O
O
O
O
O
O
O
O O O
O O O O
O
O
O
O
O
O
O O
O
O O
O
O O O
O
O
O O
O R
R
Figure 1.11. Shape-selective olefin epoxidation using dendrimers with a manganese porphyrin core as catalysts.42
Heme proteins are known to bind dioxygen either prior to activation, yielding the catalytically active oxo species, or simply for transport reasons such as in monomeric myoglobin or tetrameric hemoglobin. In an attempt to mimic oxygen binding, dendritic iron(II) porphyrins have been investigated. Jiang and Aida reported that the lifetime of the oxygen adduct dramatically increased with increasing dendritic shielding leading to 95% survival after 2 months in the case of the somewhat stiffer fifth generation dendrimer.44 The authors suggested that the more crowded dendritic poly(benzyl ether) barrier lowered the effective gas permeability and acted to reduce the entry of water molecules, therefore
19
providing both steric and hydrophobic protection to the oxygen complex. Collman, Diederich, and coworkers measured the oxygen and carbon monoxide equilibrium binding constants of their Newkome-type poly(ether amide) dendrimers using 1,2dimethylimidazole as the axial ligand to form a five-coordinate, high-spin iron(II) precursor complex.45 They found a remarkably high oxygen affinity, 1500 times greater than that of the T-state of hemoglobin. This was attributed to possible hydrogen bonding interactions of the amide protons with the terminal oxygen atom. Interestingly, the measured carbon monoxide affinity was very low. Multicopper motifs46 have also been investigated as non-heme models for oxygen carriers.47 Enomoto and Aida described the oxygen driven self-assembly of a copperligating dendrimer to yield a bis(µ-oxo)dimer (Figure 1.12).48
Figure 1.12. Dendritic non-heme dioxygen carrier. A bis(µ-oxo)copper dimer based on a triazacyclononane (TACN) – copper(II) complex is shown.48
20
The decay of the oxygen complexes was very dependent on dendrimer size, with high generation dimers displaying longer lifetimes. Kinetic analysis revealed that a more negative entropy of activation was the cause for the slower unimolecular decay. However, at a higher generation, the oxygen adduct cannot be formed at all due to the steric bulk of the dendritic subunits. The application of dendrimers in the design of sensors for sulfur dioxide gas was demonstrated with poly(phenyl ester) dendrimers bearing multiple platinum pincer complexes.49 These metalated dendritic sensors showing a direct optical response were highly selective towards sulfur dioxide and fully reversible providing the opportunity to tune detection sensitivity via variations of platinum sites. Brunner introduced dendritic ligands carrying optically active groups for enantioselective catalysis.50 The molecules, termed "dendrizymes", were designed to transfer the chiral information inherent in the dendrimer backbone over a long range to the asymmetric metal center. However, enantioselectivities were usually found to be rather low. Interestingly, in one case a 1,3,5-branched ligand led to a rate acceleration whereas the 1,2,5-isomer showed a rate retardation. This finding is in agreement with other studies mentioned earlier,20c,30 which illustrate the important effect of the dendritic branching pattern on the ultimate properties of the material. Dendritically expanded chiral ligands have been explored in asymmetric carbonyl additions. Whereas Bolm and coworkers used dendritic pyridyl alcohols (Figure 1.13a) for the asymmetric diethylzinc addition to benzaldehyde,51 Seebach and coworkers used their Taddol system.52 Yoshida et al. reported on binaphthol core dendrimers as chiral ligands in the titanium-mediated allylation of the same substrate (Figure 1.13b).53 The key result in both studies is that the 21
enantioselectivities remained constant with increasing generation. A detailed mechanistic analysis has been performed by Chow and coworkers, who investigated dendritic bis(oxazoline)copper(II) catalysts (Figure 1.13c) in Diels-Alder reactions.54 As the generation number increases, pre-complexation of the dienophile to the catalyst became increasingly difficult. The rate of the subsequent reaction of the catalyst-substrate complex with the diene remained initially constant, then dropped when changing from the second to the third generation. For the higher generation catalyst, a slightly enhanced selectivity for sterically less demanding dienophiles was observed. A similar finding was reported by van Leeuwen and coworkers, who investigated palladium catalyzed allylation reactions using a bisphospine ligand incorporated in a carbosilane dendrimer.55 Increasing the generation number of the catalysts, led to a rate decrease as well as a change in regioselectivity of the catalyst.
Figure 1.13. Dendritically modified chiral ligands for asymmetric catalysis.51,53,54
It is clear that simply building chirality into the dendritic analog of a small molecule catalyst is not sufficient to produce enzyme-like catalytic enhancements. In addition, increasing the generation number and therefore the thickness of the dendritic shell may - depending on the flexibility and exact nature of the building block - lead to 22
increasingly difficult mass transport and therefore diminished catalytic activity. Obviously, the application of more thorough design concepts including tailored microenvironments and even structural features that assist in transport and in lowering the energy of key transition states and intermediates will be required before dendritic catalysts can reach their full potential. In collaboration with Hawker, our research group has recently designed a very simple dendrimer catalyst (Figure 1.14) that incorporates design features favoring a low energy transition state while also providing for preferential entry of the reagents and thermodynamically driven exclusion of the product to avoid product inhibition of the catalytic site.56 The dendrimer behaves as a unimolecular micelle-like container with a hydrophilic interior environment that stabilizes polar transition states and intermediates, and a hydrophobic exterior that helps to solubilize the catalyst and drive product away from the catalytic site. The catalyst was tested in simple E1-type eliminations involving tertiary alkyl halides. As a result of their polarity, the alkyl halide moieties are drawn to the highly polar core, where formation of the carbocationic intermediate and subsequent elimination occurs to yield the non-polar alkene that is then rapidly driven from the core to the non-polar corona and surrounding solvent to minimize the free energy of the system. Consideration of Le Chatelier’s principle explains the high turnover number (17400) obtained as substrate is driven in and product driven out of the catalytic site of the dendrimer that functions as a catalytic “pump”. Therefore, almost quantitative conversions can be achieved with very low catalyst loading (less than 0.01 mol %). In a related approach, acid-base catalysis has been explored by Morao and Cossío, who used a
23
single tertiary amine at the core of poly(benzyl ether) dendrimers to catalyze nitroaldol reactions.57
Figure 1.14. A unimolecular reverse micelle that efficiently catalyzes the elimination of tertiary halides.56 The nonpolar corona shields the polar interior of hydroxyl-functionalities, which are able to stabilize the carbocation intermediate.
Conclusion The recent progress in the synthesis of dendrimer encapsulated molecules and their study has been discussed and key concepts, such as site isolation, light-harvesting, and catalysis at the core of dendrimers, have been introduced. The described investigations have implications that range from the preliminary design of artificial 24
enzymes, catalysts, or light harvesting systems to the construction of light emitting diodes and fiber optics. The following chapters will describe different approaches to encapsulate single functional moieties using different polymer architectures. Primarily, the synthesis of novel polymeric materials and the investigation of their properties using a variety of techniques will be discussed. Focus will be on the evaluation of site isolation within the different polymer morphologies and its application in energy harvesting and conversion in combination with catalysis.
References 1. (a) Newkome, G. R.; Moorefield, C. N.; Vögtle, F. Dendritic Molecules: Concepts, Synthesis, Perspectives, VCH: Weinheim, 1996. (b) Top. Curr. Chem. 1998, 197; 2000, 210; 2001, 212. For recent reviews consult: (c) Bosman, A. W.; Jansen, H. M.; Meijer, E. W. Chem. Rev. 1999, 99, 1665. (d) Fischer, M.; Vögtle, F. Angew. Chem. Int. Ed. 1999, 38, 885. (e) Majoral, J.-P.; Caminade, A.-M. Chem. Rev. 1999, 99, 845. (f) Matthews, O. A.; Shipway, A. N.; Stoddart, J. F. Prog. Polym. Sci. 1998, 23, 1. (g) Frey, H.; Lach, C.; Lorenz, K. Adv. Mater. 1998, 10, 279. (h) Fréchet, J. M. J.; Hawker, C. J. In Comprehensive Polymer Science, 2nd Suppl.; Aggarwal, S. L.; Russo, S., Eds.; Pergamon Press: Oxford, 1996, p 140. 2. A comprehensive review on functional dendrimers is given by: (a) Chow, H.-F.; Mong, T. K.-K.; Nongrum, M. F.; Wan, C.-W. Tetrahedron 1998, 54, 8543. For other reviews, see: (b) Fréchet, J. M. J. Science, 1994, 263, 1710. (c) Smith, D. K.;
25
Diederich, F. Chem. Eur. J. 1998, 4, 1353. (d) Archut, A.; Vögtle, F. Chem. Soc. Rev. 1999, 27, 233. 3. The use of self-assembly to construct supramolecular dendritic structures is reviewed in: (a) Zeng, F.; Zimmerman, S. C. Chem Rev. 1997, 97, 1681. (b) Emrick, T.; Fréchet, J. M. J. Curr. Opin. Coll. In. Sci 1999, 4, 15. (c) Newkome, G. R.; He, E.; Moorefield, C. N. Chem. Rev. 1999, 99, 1689. (d) Venturi, M.; Serroni, S.; Juris, A.; Champagna, S.; Balzani, V. Top. Curr. Chem. 1998, 197, 193. 4. (a) Cytochrome P-450: Structure, Mechanism and Biochemistry; Ortiz de Montellano, P.; Ed.; Plenum Press: New York, 1995. (b) Top. Curr. Chem. 1996, 184. 5. Moore, G. R.; Pettigrew, G. W.
Cytochromes-c: Evolutionary, Structural, and
Physicochemical Aspects, Springer: Berlin, 1990. 6. For instance, see: Stephens, P. J.; Jollie, D. R.; Warshel, A. Chem. Rev. 1996, 96, 249. 7. McDermott, G.; Prince, S. M.; Freer, A. A.; Hawthornethwalte-Lawless, A. M.; Papiz, M. Z.; Cogdell, R. J.; Isaacs, N. W. Nature 1995, 374, 517. 8. Property variation has been greatly facilitated by the advent of combinatorial chemistry. Recently, this powerful technique has been applied successfully to materials discovery. For recent reviews, see: (a) Jandeleit, B.; Schaefer, D. J.; Powers, T. S.; Turner, H. W.; Weinberg, W. H. Angew. Chem. Int. Ed. 1999, 38, 2494. (b) Schultz, P. G.; Xiang, X. D. Curr. Opin. Solid State Mater. Sci. 1998, 3, 153. 9. An example of direct variation of molecular properties has elegantly been described in a recent review about π-conjugated oligomers: Martin, R. E.; Diederich, F. Angew. Chem. Int. Ed. 1999, 38, 1350. 26
10 Examples include references: 11, 12, 14, 26, 27, 29. 11. Pollak, K. W.; Sanford, E. M.; Fréchet, J. M. J. J. Mater. Chem. 1998, 8, 519. 12. Karakaya, B.; Claussen, W.; Gessler, K.; Saenger, W.; Schlüter, A. D. J. Am. Chem. Soc. 1997, 119, 3296. 13. Cylindrically shaped dendrimers have recently been reviewed in: (a) Schlüter, A. D.; Rabe, J. P. Angew. Chem. Int. Ed. 2000, 39, 864. (b) Schlüter, A. D. Top. Curr. Chem. 1998, 197, 165. 14. Stocker, W.; Karakaya, B.; Schürmann, B. L.; Rabe, J. P.; Schlüter, A. D. J. Am. Chem. Soc. 1998, 120, 7691. 15. (a) Hawker, C. J.; Wooley, K. L.; Fréchet, J. M. J. J. Am. Chem. Soc. 1993, 115, 4375. (b) Devadoss, C.; Bharathi, P.; Moore, J. S. Angew. Chem. Int. Ed. 1997, 36, 1633. (c) Smith, D. K.; Müller, L. Chem. Commun. 1999, 1915. 16. De Backer, S.; Prinzie, Y.; Verheijen, W.; Smet, M.; Desmedt, K.; Dehaen, W.; De Schryver, F. C. J. Phys. Chem. A 1998, 102, 5451. 17. See for example: Turro, N. J.; Barton, J. K.; Tomalia, D. A. Acc. Chem. Res. 1991, 24, 332. 18. For recent reviews consult: (a) Boulas, P. L.; Gómez-Kaifer, M.; Echegoyen, L. Angew. Chem. Int. Ed. 1998, 37, 217. (b) Cardona, C. M.; Mendoza, S.; Kaifer, A. E. Chem. Soc. Rev. 2000, 29, 37. 19. Gorman, C. B.; Hager, M. W.; Parkhurst, B. L.; Smith, J. C. Macromolecules 1998, 31, 815. 20. (a) Tomoyose, Y.; Jiang, D.-L.; Jin, R.-H.; Aida, T.; Yamashita, T.; Horie, K.; Yashima, E.; Okamoto, Y. Macromolecules 1996, 29, 5236. (b) Jiang, D.-L.; Aida, 27
T. Nature 1997, 388, 454. (c) Jiang, D.-L.; Aida, T. J. Am. Chem. Soc. 1998, 120, 10895. 21. (a) Kamlet, M. J.; Abboud, J. M.; Abraham, M. H.; Taft, R. W. J. Org. Chem. 1983, 48, 2877. (b) Reichardt, C. Solvents and Solvent Effects in Organic Chemistry, 2nd edn., VCH: Weinheim, 1990. 22. Jin, R.-H.; Aida, T.; Inoue, S. J. Chem. Soc., Chem. Commun. 1993, 1260. 23. Pollak, K. W.; Leon, J. W.; Fréchet, J. M. J.; Maskus, M.; Abruña, H. D. Chem. Mater. 1998, 10, 30. 24. Sadamoto, R.; Tomioka, N.; Aida, T. J. Am. Chem. Soc. 1996, 118, 3978. 25. Tomioka, N.; Takasu, D.; Takahashi, T.; Aida, T. Angew. Chem. Int. Ed. 1998, 37, 1531. 26. (a) Issberner, J.; Vögtle, F.; De Cola, L.; Balzani, V. Chem. Eur. J. 1997, 3, 706. (b) Vögtle, F.; Plevoets, M.; Nieger, M.; Azzellini, G. C.; Credi, A.; De Cola, L.; De Marchis, V.; Venturi, M.; Balzani, V. J. Am. Chem. Soc. 1999, 121, 6290. 27. Related dendritic phenanthroline complexes have been described in: (a) Serroni, S.; Campagna, S.; Juris, A.; Venturi, M.; Balzani, V.; Denti, G. Gazz. Chim. Ital. 1994, 124, 423. (b) Tzalis, D.; Tor, Y. Tetrahedron Lett. 1996, 37, 8293. 28. (a) Brewis, M.; Clarkson, G. J.; Goddard, V.; Helliwell, M.; Holder, A. M.; McKeown, N. B. Angew. Chem. Int. Ed. 1998, 37, 1092. (b) McKeown, N. B. Adv. Mater. 1999, 11, 67. 29. Additional references on phthalocyanine core dendrimers include: (a) Kimura, M.; Nakada, K.; Yamaguchi, Y.; Hanabusa, K.; Shirai, H.; Kobayashi, N. Chem. Commun. 1997, 1215. (b) Brewis, M.; Clarkson, G. J.; Holder, A. M.; McKeown, N. 28
B. Chem. Commun. 1998, 696. (c) Ng, A. C. H.; Li, X.-Y.; Ng, D. K. P. Macromolecules 1999, 32, 5292. (d) Kimura, M.; Sugihara, Y.; Muto, T.; Hanabusa, K.; Shirai, H.; Kobayashi, N. Chem. Eur. J. 1999, 5, 3495. 30. Kawa, M.; Fréchet, J. M. J. Chem. Mater. 1998, 10, 286. 31. (a) Junge, D. M.; McGrath, D. V. Chem. Commun. 1997, 857. (b) Junge, D. M.; McGrath, D. V. J. Am. Chem. Soc. 1999, 121, 4912. 32 The
concept
of
light-induced
control
over
structure
and
function
of
(bio)macromolecules has been reviewed by: Willner, I.; Rubin, S. Angew. Chem. Int. Ed. Engl. 1996, 35, 367. 33. Adronov, A.; Fréchet, J. M. J. Chem. Commun. 2000, 1701. 34. (a) Gilat, S. L.; Adronov, A.; Fréchet, J. M. J. Angew. Chem. Int. Ed. 1999, 38, 1422. (b) Adronov, A.; Gilat, S. L.; Fréchet, J. M. J.; Ohta, K.; Neuwahl, F. V. R.; Fleming, G. R. J. Am. Chem. Soc. 2000, 122, 1175. (c) Adronov, A.; Malenfant, P. R. L.; Fréchet, J. M. J. Chem. Mater. 2000, 12, 1463. (d) Plevoets, M.; Vögtle, F.; De Cola, L.; Balzani, V. New J. Chem. 1999, 63. (e) Stewart, G. M.; Fox, M. A. J. Am. Chem. Soc. 1996, 118, 4354. 35. (a) Xu, Z.; Moore, J. S. Acta Polymer. 1994, 45, 83. (b) Devadoss, C.; Bharathi, P.; Moore, J. S. J. Am. Chem. Soc. 1996, 118, 9635. (c) Campagna, S.; Denti, G.; Serroni, S.; Ciano, M.; Juris, A.; Balzani, V. Inorg. Chem. 1992, 31, 2982. (d) Campagna, S.; Denti, G.; Serroni, S.; Juris, A.; Venturi, M.; Ricevuto, V.; Balzani, V. Chem. Eur. J. 1995, 1, 211. (e) Serroni, S.; Juris, A.; Venturi, M.; Campagna, S.; Resino, I. R.; Denti, G.; Credi, A.; Balzani, V. J. Mater. Chem. 1997, 7, 1227. (f) Balzani, V.; Campagna, S.; Denti, G.; Juris, A.; Serroni, S.; Venturi, M. Acc. Chem. 29
Res. 1998, 31, 26. (g) Li, F.; Yang, S. I.; Ciringh, Y.; Seth, J.; Martin, C. H.; Singh, D. L.; Kim, D.; Birge, R. R.; Bocian, D. F.; Holten, D.; Lindsey, J. S. J. Am. Chem. Soc. 1998, 120, 10001. 36. Wang, P.-W.; Liu, Y.-J.; Devadoss, C.; Bharathi, P.; Moore, J. S. Adv. Mater. 1996, 8, 237. 37. Halim, M.; Pillow, J. N. G.; Samuel, I. D. W.; Burn, P. L. Adv. Mater. 1999, 11, 371. 38. Freeman, A. W.; Koene, S. C.; Malenfant, P. R. L.; Thompson, M. E.; Fréchet, J. M. J. J. Am. Chem. Soc. 2000, 122, 12385. 39. Some representative reviews about artificial enzymes include: (a) Murakami, Y; Kikuchi, J.-i.; Hisaeda, Y.; Hayashida, O.
Chem. Rev. 1996, 96, 721. (b)
"Bioinorganic Enzymology", Chem. Rev. 1996, 96, issue 7. (c) Karlin, K. D. Science, 1993, 261, 701. 40. For a review about dendrimers having multiple catalytically active sites at the periphery, see: reference 2a. Contrary to conventional homogeneous catalysts, such systems offer the advantage of convenient removal by filtration techniques. 41. (a) Metalloporhyrins in Catalytic Oxidations; Sheldon,R. A.; Ed.; Marcel Dekker: New York, 1994. (b) Metalloporphyrin Catalyzed Oxidations; Montanari, F.; Casella, L.; Eds.; Kluwer: London, 1995. (c) Sono, M.; Roach, M. P.; Coulter, E. D.; Dawson, J. H. Chem. Rev. 1996, 96, 2841. (d) Suslick, K. S.; van Deusen-Jeffries S. In Comprehensive Supramolecular Chemistry, Vol. 5, Lehn, J.-M.; Ed.; Elsevier: London, 1996.
30
42. (a) Bhyrappa, P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Am. Chem. Soc. 1996, 118, 5708. (b) Bhyrappa, P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Mol. Catal. A 1996, 113, 109. 43. Shape-selective ligation of various nitrogeneous bases to similar dendritic zinc porphyrins is described in: Bhyrappa, P.; Vaijayanthimala, G.; Suslick, K. S. J. Am. Chem. Soc. 1999, 121, 262. 44. Jiang, D.-L.; Aida, T. Chem. Commun. 1996, 1523. 45. Collman, J. P.; Fu, L.; Zingg, A.; Diederich, F. Chem. Commun. 1997, 193. 46. Multicopper oxidases and oxygenases have been thoroughly reviewed by: Solomon, E. I.; Sundaram, U. M.; Machonkin, T. E. Chem. Rev. 1996, 96, 2563. 47. Multi-O2 complexes based on copper bis[2-(2-pyridyl)ethyl]amine-terminated poly(propylene imine) dendrimers having the oxygen binding sites located at the periphery have been reported by: Gebbink, R. J. M. K.; Bosman, A. W.; Feiters, M. C.; Meijer, E. W.; Nolte, R. J. M. Chem. Eur. J. 1999, 5, 65. 48. Enomoto, M.; Aida, T. J. Am. Chem. Soc. 1999, 121, 874. 49. (a) Albrecht, M.; van Koten, G.
Adv. Mater. 1999, 11, 171. (b) Albrecht, M.;
Gossage, R. A.; Lutz, M.; Spek, A. L.; van Koten, G. Chem. Eur. J. 2000, 6, 1431. 50. Brunner, H. J. Organomet. Chem. 1995, 500, 39. 51. Bolm, C.; Derrien, N.; Seger, A. Synlett 1996, 387. 52. Rheiner, P. B.; Seebach, D. Chem. Eur. J. 1999, 5, 3221. 53. Yamago, S.; Furukuwa, M.; Azuma, A.; Yoshida, J.-I. Tetrahedron Lett. 1998, 39, 3783.
31
54. a) C. C. Mak, H.-F. Chow, Macromolecules 1997, 30, 1228-1230. b) H.-F. Chow, C. C. Mak, J. Org. Chem. 1997, 62, 5116-5127. 55. G. E. Oosterom, R. J. van Haaren, J. N. H. Reek, P. C. J. Kamer, P. W. N. M. van Leeuwen, Chem. Commun. 1999, 1119-1120. 56. M. E. Piotti, F. Rivera, R. Bond, C. J. Hawker, J. M. J. Fréchet, J. Am. Chem. Soc. 1999, 121, 9471-9472. 57. I. Morao, F. P. Cossío, Tetrahedron Lett. 1997, 36, 6461-6464.
32
Chapter 2:
An Alternative Synthetic Approach to Dendritic Macromolecules Utilizing an Alkyne Cyclotrimerization Reaction
Abstract Dendrimers consisting of benzene rings bearing six dendritic wedges have been constructed in a single step using a cobalt-mediated [2+2+2] cycloaddition reaction. Among the advantages of this approach to the construction of precise macromolecular structures are great synthetic versatility, ease of purification, as well as tolerance of a variety of functional groups. According to NMR relaxation time experiments, the benzene core dendrimers exhibit an unexpectedly high flexibility around the core unit. This chapter has been reproduced in part with permission from J. Am. Chem. Soc. 1999, 121, 4084-4085. Copyright 1999 American Chemical Society.
33
Introduction In the convergent growth approach1 towards dendrimer2 synthesis, dendrons are usually covalently attached to a core molecule in the very last step to afford the desired dendritic macromolecule. Due to the increasing steric crowding around the focal point of higher generation dendrons and therefore decreased accessibility of the functional group, these coupling reactions are frequently difficult to perform. Several approaches have been sought to overcome this problem, including the use of extended cores, such as 1,1,1tris(4’-hydroxyphenyl)ethane,1 as well as branched cores in combination with lower generation dendrons.3 Furthermore, elegant synthetic protocols have been developed recently that covalently access the core moiety from respective dendritic precursors in the final step of the sequence.4 This direct method usually facilitates chromatographic purification owing to a more pronounced difference in elution behavior of substrates vs. products. The inherent perfect dendritic coverage renders this approach especially useful for the synthesis of cylindrical dendrimers5 via a dendritic macromonomer route. In addition, many chemical transformations used in dendrimer chemistry today are intolerant of a variety of functionalities. For these reasons, a new way to access dendrimers with highly congested cores was developed. We report an alternative method for the convergent synthesis of dendrimers in which the dendrimer core is generated from a dendritic precursor by a transition metal mediated alkyne cyclotrimerization reaction.6 In this method, convergent dendrons1 attached to an acetylenic moiety are cyclized in a [2+2+2] cycloaddition process. If carried out with a difunctionalized dendritic alkyne, this reaction affords a benzene moiety surrounded by six dendrons as depicted in Figure 2.1. 34
Figure 2.1. [2+2+2] Cycloaddition of symmetrical bis(dendritic)alkyne precursors leads to benzene core dendrimers carrying six dendritic wedges.
As an example, a third generation poly(benzyl ether) dendrimer is shown in Scheme 2.1 and the retrosynthetic disconnections are shown. Scheme 2.1
O
O
OO
O
O
O
O O
O O
OO
O
O
OO
O O
O O O
O
O O
O O
O O
O
O O
O
O
O O
O O
O
O
O O
O O
O O
O O O O
O
O
O O
O
O
O
O
O
O
O
O O
O O
O
O O
O O
O
O O
OO
O O
OO
O O
O O
O O
O
OO
35
O
O
Results and Discussion Synthesis. The [2+2+2] cycloaddition reaction can be mediated by various catalysts, mostly consisting of late transition metals, such as Co, Ni, Pd.6 The high affinity of the transition metal complexes for triple bonds results in a high degree of chemoselectivity, therefore rendering the reaction tolerant of many functional groups. We focused on using dicobalt octacarbonyl, Co2(CO)8,7 as the catalyst since it is commercially available, fairly robust and therefore easy to handle, operates in a variety of different solvents,8 and requires low loadings of typically 5 mol % or less. The catalytic cycle7 involves formation of the initial tetrahedral dinuclear cobalt complex 1, followed by a second alkyne addition to afford the metallacyclopentadiene 2 and subsequent alkyne insertion to give the “flyover” complex 3,9 which generates the desired benzene derivative after reductive elimination (Scheme 2.2). The relatively high stability of 3 was demonstrated by its detection in the matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectra of the reaction mixtures. Due to the second insertion step and the thermodynamic preference of the 1,4-disubstituted complex 2, the cyclotrimerization reactions exhibits a high degree of 1,2,4-regiochemical control. There have been only few examples of preferred formation of 1,3,5-trisubstituted benzenes involving relatively sensitive catalysts.10 Not unexpectedly, cyclotrimerization of benzyl propargyl ether 4 gave a inseparable mixture of regioisomers 5 and 6 (Scheme 2.3). Therefore, to avoid the formation of different regioisomers, symmetrical alkyne precursors were used. Somewhat related approaches were used by Duchêne and Vögtle for the synthesis of a dodecafunctionalized host-molecule11 as well as by Kaufman and Sidhu to prepare benzene derivatives carrying six carbohydrate substituents.12 36
Scheme 2.2 Co2(CO)8 R
- 2 CO
R R
R
(CO)3Co
R
Co(CO)3
1
R - CO
+ 2 CO
R
R (CO)2Co
Co(CO)2
R
(CO)2Co
R
R
R Co(CO)3
2
3 - CO
R
Scheme 2.3 OBn BnO
Co2(CO)8
OBn
∆ (toluene) 34%
4
OBn
+
BnO OBn
BnO
5
~1:1
6
An acetylenic system consisting of benzylic ethers of 2-butyne-1,4-diol was chosen for commercial availability as well as its synthetic compatibility. In particular, this linkage prevents the occurrence of a Claisen rearrangement arising from either alkynyl benzyl ether13 or phenyl propargyl ether connectivities.14 The substituted alkynes 8a-d were obtained by the Williamson ether coupling of 2-butyne-1,4-diol with the appropriate 37
poly(benzyl ether)-type1 dendritic bromides 7a-d (Scheme 2.4). The trimerization reaction of 8a-d was carried out in refluxing toluene using Co2(CO)8 as the catalyst to afford the novel structures 9a-d. Scheme 2.4
R-Br
HO
OR
OR
NaH Co2(CO)8
OH
50 oC (DMF)
OR ∆ (toluene)
RO
OR
O OR
9a-d
8a-d
Bn
R=
RO RO
7a-d
O
Bn
n [G-n] (n = 1 - 3) a: R = Bn b: R = Bn2[G-1] c: R = Bn4[G-2] d: R = Bn8[G-3]
As expected, the time required to complete the trimerization reaction increased with generation (Table 2.1) while the yield decreased as a result of steric crowding around the nascent core. It should be noted that the yields correspond to chemical conversion since only remaining starting material was isolated. Table 2.1.
Synthesis of Dendritic Alkynes 8a-d and Benzene Core Dendrimers 9a-d.
compound
R
yield of 8
yield of 9
time 8→9
a
Bn
62 %
83 %
0.5 h
b
Bn2[G-1]
62 %
80 %
2h
c
Bn4[G-2]
50 %
50 %
20 h
d
Bn8[G-3]
41 %
36 %
48 h
Since the poly(benzyl ether) dendrons are crucial building blocks for the synthesis of several compounds discussed throughout the first chapters, their preparation involving either conventional convergent growth by repetitive coupling and activation steps1 or accelerated growth using a branched monomer15 is shown in Scheme 2.5. 38
Scheme 2.5
HO
OH
HO
OH
O
OH
O
1. K2CO3, 18-crown-6 ∆ (acetone) Br
O
OH
2. CBr4, PPh3 rt (THF)
O
1. K2CO3, 18-crown-6 ∆ (acetone) 2. CBr4, PPh3 rt (THF)
Br O
Br O O
O
Bn2[G-1]Br
Bn4[G-2]Br
7b OTBDPS
OTBDPS
OTBDPS
TBDPSO
TBDPSO
OTBDPS O
OTBDPS O
O
7c
OTBDPS
O
10 OH
OH
1. KF, K2CO3, 18-crown-6, ∆ (acetone)
1. KF, K2CO3, 18-crown-6, ∆ (acetone)
2. CBr4, PPh3, rt (THF)
2. CBr4, PPh3, rt (THF)
O O O O
O O O
O
O
O
O O O
O
O O
O O
O
O
Br
O
O
O
O
Br
O
O
O
O
O O O
O
O
O
O O
O
O O
O
O O O
Bn8[G-3]Br
O
7d
Bn16[G-4]Br 7e
39
To our knowledge, this represents the first time that such large and precisely defined macromolecules (MW ~ 10,000 for 9d) have been successfully prepared by a cyclotrimerization reaction. Because of the nature of the transformation, the reaction is extremely clean and no partially reacted products can be formed. Therefore, aside from recovered starting materials, compounds 9a-d were the only products isolated after reaction resulting in their greatly facilitated purification by column chromatography. Characterization. Benzene core dendrimers 9a-d have been fully characterized by various techniques. MALDI-TOF mass spectra and size exclusion chromatography traces confirm the monodisperse nature of the compounds and their high purity (Figure 2.2). 2095 (2095)
(a)
9b 4644 (4642)
9c 9739 (9736)
9d 2000
3000
4000
5000
6000
7000
8000
9000
10000
mass (m/z) / amu →
9b
(b)
9c 9d
20
25
30
35
GPC elution time / min
Figure 2.2. (a) MALDI-TOF mass spectra (as Na+ adducts) and (b) GPC traces of compounds 9b-d.
40
To probe their solution dynamics, NMR relaxation time (T1) measurements were performed. Herein, a correlation of the relaxation behavior of the spectroscopic probe, i.e. the proton, with its local environment can be used to gain information about the relative density distribution within the macromolecule.16 Because of the high spectral resolution allowing clear observation of the different layers (Scheme 2.6) of the structure, this approach was used to gain information about the entire dendrimer framework. Scheme 2.6 H5 O
O
O
OO
O
H2C
O
O
e
O
O
OO
H2C O
O
O O
H2C
O O
O
d
O
O
O
c
O
b
O
O O
O
O O
O
O
O
O O O
O O
O
O
O O
OO
O
O
O
O
O
O
O O O
O O
O
O
O
O
O
O
O
OO
O
O
O
O
O
O
O
O
O
O O
O
O
O O
O
O
O
O
O
O
O O
OO
b
O
O
O
O
O
O
d
O
O
O
H2C
c
f
e
O
O O
O C H2
C H2
O
aO
O
O
H 2C O
O
O O
H5
O
O
O O
CH2
O
O O
CH2 O O
O
O
O
OO
O
O
O
O
O
O
O
O
O O
f
O
O
9d
11
As shown in Figure 2.3, the T1 values for the terminal benzylic protons (e) are almost constant while a slight decrease in T1 is observed for the exterior phenyl protons (f). This suggests that there is no change in steric congestion at the periphery of the dendrimer as the generation increases. The relaxation times for the successive layers within the dendrimer decrease from the core to the periphery suggesting a radial increase in density of the macromolecule.
41
2.5
Relaxation Time (T1) / s
2
1.5
1
0.5 11 9d 9c 9b
0 a
b
c
d
e
f
Proton Signal Figure 2.3.
1
H NMR spin-lattice relaxation times (T1) of compounds 9b-d and 11, as external reference, in CDCl3 at 298 K (proton assignments refer to Scheme 2.6.
This finding fits the simplified model of de Gennes and Hervet17 and somewhat contradicts the theory of Lescanec and Muthukumar.18 More sophisticated models predict a large degree of backbonding of the outer dendritic wedges19 that will largely depend on the flexibility of the actual dendritic structure. However, no such modeling results are available for poly(benzyl ether) dendrimers. A comparison with the model tridendron molecule 111 reveals a similar trend in T1 values. Our findings are also in agreement with those of Aida and coworkers,16 who reported that the protons at the periphery of higher generation dendrimers exhibit shorter relaxation times suggesting that their local environment is more congested than that of the core. Surprisingly, the T1 values of the benzylic protons nearest the core almost double with each successive generation. This unprecedented observation suggests enhanced flexibility at the core as the molecule 42
becomes larger. Perhaps the molecules adopt more extended conformations to accommodate the rapidly increasing steric requirements of the larger dendrons. A comparison with reference compound 11 suggests that the presence of an additional methylene unit (a) in 9c is responsible for this additional mobility. The encapsulation of the central benzene moiety is illustrated by the molecular model shown in Figure 2.4. Furthermore, the dimensions of the molecule spanning approximately 5 nm are noteworthy.
Figure 2.4. Molecular model of compound 9d (MM2 molecular mechanics calculation). The central benzene moiety is shown in black.
43
Synthetic Scope and Limitations. Due to its inherent high tolerance of functional groups, the versatility of the [2+2+2] cycloaddition approach was explored. Hence, two first generation dendrons, prepared from methyl 3,5-dihydroxybenzoate 12 in 50 % yield over four steps, having acetal protected phenolic groups at their periphery were attached to 2-butyne-1,4-diol to afford 13 (Scheme 2.7). It should be noted that the 3,5tetrahydropyranyloxy-substituents have a strongly electron donating effect on the aromatic ring, so that the compounds having a good leaving group at the benzylic position tend to decompose quickly by polymerization via self-alkylation.20 Cyclotrimerization of 13 proceeded smoothly in the presence of the acetals to yield 14. However, 14 could not be deprotected successfully to lead to 15, a potentially interesting dodecasubstituted core molecule, and gave yet unknown decomposition products. Scheme 2.7 HO
OH
1. DHP, PTSA (CH2Cl2) 2. KBH4, LiCl, ∆ (THF) 3. CBr4, PPh3, (i-Pr)2EtN (THF) 4. NaH,
O
HO
OTHP
OTHP
THPO
OH
O
OMe 50%
12
O
13
OTHP THPO
THPO
OTHP OTHP
OTHP
O
O
Co2(CO)8 ∆ (toluene)
OTHP
O O
THPO
65%
O
O
OTHP
THPO THPO OTHP
OTHP
14
44
H+
(HO)12[G-1]benzene
15
Encouraged by these results but limited by the strongly basic and only moderately yielding Williamson etherification conditions, necessary for the preparation of the 2butyne-1,4-diether precursors, efforts toward changing the linkage chemistry from ethers to ester were made (Scheme 2.8). Scheme 2.8 O
O
O
O
O
BnO
1.
OBn
DMAP, ∆ (CH3CN) HO
OH
O
2. (COCl)2, DMF (CH2Cl2) 3. BnOH, pyridine (CH2Cl2)
Co2(CO)8
O
O
O
no reaction
∆ (toluene)
16
70%
O O OH
HO O
O
CO2H DCC, DPTS
O O
O O
O
17
51%
18
O
∆ (toluene) 44%
O
O
Co2(CO)8
(CH2Cl2)
O
O
O
O
O O
O
O O
O
O O
O
O
19
2-Butyne-1,4-diol was converted into a dicarboxylic acid by reacting both alcohol termini with succinic anhydride. Model compound 16 was conveniently prepared by esterification using the corresponding acid chloride. However, cyclotrimerization completely failed and no reaction was observed. Presumably, the ester carbonyl functionalities coordinate to the cobalt catalyst thereby interfering with the reaction. Therefore, the ester linkages were further removed from the reacting triple bond using ethylene glycol elongated alkyne diol 17 and model compound 18 was synthesized via carbodiimide-mediated esterification. Cyclotrimerization of 18 was successful and 19
45
could be isolated in 44 % yield. This result is encouraging and demonstrates the possibility of synthesizing more complex structures using the milder esterification coupling chemistry. However, a significant drawback to this route is that the commercially available compound 17 contains 4-(2-hydroxyethoxy)-2-butynol as a major impurity rendering the synthesis and purification of ester derivatives of 17 rather difficult. To explore the potential of the cyclotrimerization route for the synthesis of more functional molecules, alkyne precursors having porphyrin substituents were investigated. An asymmetric porphyrin building block (20) was reacted with 2-butyne-1,4-diol under Mitsunobu coupling conditions and the free-base porphyrins metalated to afford mono(zinc porphyrinyl)alkyne 21 and bis(zinc porphyrinyl)alkyne 22 (Scheme 2.9). Scheme 2.9 H N
3 CHO
+ OMe
HO
1.
N
o
120 C (EtCO2H, PhNO2) o
2. BBr3, 0 C (CH2Cl2)
N
DIAD, PPh3 (CH2Cl2, THF) 2. Zn(OAc)2, ∆ (CHCl3, MeOH)
N
NH
OH
1.
HN
6.3%
N Zn N
N
77%
1 CHO OH
O
20 HO
OH
1.
OH
DIAD, PPh3 (CH2Cl2, THF) 2. Zn(OAc)2 ∆ (CHCl3, MeOH)
21
82%
N
N Zn
N
N O
O
N
N
22
46
N Zn N
Subsequent cyclotrimerization, however, did not yield the desired zinc porphyrin substituted benzene derivatives. Instead mostly no reaction occurred and some free phenol 20 was formed. This supports the initial assumption that phenyl propargyl ether might be labile under the reaction conditions.14 Interestingly, the free-base derivative of 21 led to cyclotrimerization products as evidenced by MALDI-TOF mass spectrometry, but cobalt insertion occurred as well trapping the active catalyst.
Conclusion The cyclotrimerization of bisdendritic alkynes has been demonstrated to be of synthetic use in the construction of novel benzene-cored dendrimers. Dendrimer assembly via ‘in-situ’ generation of the core molecule makes this a versatile approach for the construction of precise macromolecular structures. This approach benefits from the ease of purification of the trimerized product and its tolerance toward a variety of functional groups. The synthesized hexasubstituted benzenes, although sterically rather congested, experience an unexpectedly high degree of conformational freedom at the core region as indicated by NMR spin-lattice relaxation experiments. The major limitation of the approach is that it only affords benzene core dendrimers, thereby not allowing encapsulation of more complex and functional cores.
Experimental General Methods: All reagents were used as received and without further purification, unless otherwise noted. THF was distilled under N2 over sodium/benzophenone prior to use. Column chromatography was carried out with Merck silica gel for flash columns, 47
230-400 mesh. NMR spectra were recorded on Bruker AMX-300 (300 MHz) or Bruker DRX-500 (500 MHz) instruments with TMS or solvent carbon signal as the standards. The T1 values were measured by standard 180-τ-90
o
acquisition techniques (25 oC,
CDCl3, 500 MHz). The experimental error was estimated to be ±10 %. IR spectra were recorded on a Mattson Genesis Series FTIR. Electronic absorption spectra were recorded on a Cary 50 UV-Visible Spectrophotometer. Matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was performed on a PerSeptive Biosystems Voyager-DE spectrometer equipped with a nitrogen laser (337 nm) in delayed extraction mode and an acceleration voltage of 20 keV. Samples were prepared using a 1:20 ratio of analyte (5 mg/mL in THF) to matrix solution (trans-3-indoleacrylic acid, 10 mg/mL in THF, or α-cyano-4-hydroxycinnamic acid, saturated in THF). Elemental analyses were performed by MHW laboratories. GPC measurements were performed on a Waters 150CV plus GPC system equipped with a differential refractive index detector and a M486 UV detector (254 nm detection wavelength) using THF as the mobile phase at 45 oC and a flow rate of 1 mL/min. The samples were separated through four 5 µm PL Gel columns (Polymer Laboratories) with porosities of 100 Å, 500 Å, 1000 Å and mixed C. The columns were calibrated with 18 narrow polydispersity polystyrene samples.
General Procedure for Preparation of Benzyl-terminated Dendritic Bromides 7b-e: Benzyl-terminated Dendritic Alcohols.1 The appropriate benzylic bromide dendron (2.05 equiv.) and 3,5-dihydroxybenzyl alcohol (1 equiv., 0.1 M) were dissolved in a mixture of dried K2CO3 (4 equiv.) in dry acetone. 18-crown-6 (0.1 equiv.) was added and it was heated at 50 ºC under vigorous stirring for 12-48 h. The mixture was allowed to 48
cool and evaporated to dryness under reduced pressure. The residue was taken up in CH2Cl2, filtered over celite, and the solvent removed in vacuo. The crude product was purified either by recrystallization from cyclohexane/CH2Cl2 for lower generation dendrons or by flash chromatography (silica gel, CH2Cl2/methanol mixtures) for higher generation dendrons. Yields were consistently >90 %. Characterizational data agreed with those published.1
Higher Generation Dendritic Alcohols.1 The branched monomer 1115 (1 equiv., 0.03 M) and the appropriate dendritic bromide (4.1 equiv.) were dissolved in a suspension of K2CO3 (5 equiv.) in acetone. Then, KF (8 equiv.) and 18-crown-6 (0.1 equiv.) were added and the mixture heated at 50 ºC. The progress of the reaction was monitored by MALDITOF MS. After driving the reaction to completion the solvent was evaporated, the residue taken up in CH2Cl2, filtered over celite, and the solvent removed in vacuo. The crude product was purified by flash chromatography (silica gel, CH2Cl2/methanol mixtures). Yields were ~95 %. Characterizational data agreed with those published.1
Benzyl-terminated Dendritic Bromides 7b-e.1 A mixture of the appropriate dendritic alcohol (1 equiv.) and carbon tetrabromide (1.25 equiv.) in the minimum amount of dry THF was cooled to 0 ºC. Triphenylphosphine (1.25 equiv.) was added slowly, the ice-bath removed, and stirring was continued until the solution turned yellow (∼20 min). The reaction mixture was immediately poured into water and the aqueous layer extracted with CH2Cl2. The combined organic phases were dried over MgSO4 and the solvent evaporated under reduced pressure. The crude product was dissolved in the minimum 49
amount CH2Cl2 and precipitated by dilution with methanol. Further purification by flash chromatography (silica gel, CH2Cl2/hexanes mixtures) was necessary for higher generation dendrons. Yields of ∼85 % were obtained. Characterizational data agreed with those published.1
Preparation of 3,5-Bis{3’,5’-di(t-butyldiphenylsiloxy)benzyloxy}benzyl alcohol 11:15 Methyl 3,5-di(t-butyldiphenylsiloxy)benzoate. Methyl 3,5-dihydroxybenzoate (5.04 g, 30.0 mmol) and t-butyldiphenylsilyl chloride (17.1 ml, 66.0 mmol) were dissolved in 60 mL of DMF. The solution was cooled to 0 °C and imidazole (8.99 g, 132 mmol) added in small portions. The mixture was allowed to warm to room temperature and stirred for 22 h. The solvent was removed in vacuo, the residue taken up in 300 mL of ether, and 100 mL of water added. The aqueous layer was thoroughly extracted with ether, the combined organic phases washed with 1 M HCl (3x100 mL), 1M NaOH (3x100 mL), and brine, dried over MgSO4, and the solvent evaporated. A yellow viscous oil was obtained (19.3 g, 100 %). 1H NMR (300 MHz, CDCl3, 25 oC, TMS) δ 7.49 (d, 3J (H,H) = 9 Hz, 8 H), 7.35 (m, 4H), 7.25 (dd, 3J (H,H) = 9 Hz, 6 Hz, 8 H), 7.04 (d, 3J (H,H) = 3 Hz, 2 H), 6.27 (dd, 3J (H,H) = 3 Hz, 3 Hz, 1 H), 3.77 (s, 3 H), 1.04 (s, 18 H). 3,5-Di(t-butyldiphenylsiloxy)benzyl alcohol. Under inert gas atmosphere a suspension of lithium aluminum hydride (1.20 g, 31.5 mmol) in 10 mL of dry THF was cooled to 0 °C. A solution of methyl 3,5-di(t-butyldiphenylsiloxy)benzoate (19.3 g, 30.0 mmol) in 50 mL of dry THF was added slowly. The mixture was heated at 60 °C for 1 h. (Careful monitoring of the reaction is necessary to avoid cleavage of the silyl protecting groups.) It was quenched with sat. Na2SO4 and the THF was removed. The residue was taken up in 50
ether and a filtration followed. The filtrate was washed with water and brine, dried over MgSO4, and the solvent evaporated. The crude product was purified by flash chromatography (silica gel, 20 % ethyl acetate in hexanes) and after solvent evaporation, it was stirred with pentane for 10 h. The product was obtained as a white powder (12.3 g, 67 %). 1H NMR (500 MHz, CDCl3, 25 oC, TMS) δ 7.53 (d, 3J (H,H) = 13 Hz, 8 H), 7.35 (m, 4 H), 7.26 (dd, 3J (H,H) = 13 Hz, 13 Hz, 8 H), 6.32 (d, 3J (H,H) = 3 Hz, 2 H), 6.10 (dd, 3J (H,H) = 3 Hz, 3 Hz, 1 H), 4.32 (d, 3J (H,H) = 10 Hz, 2 H), 1.22 (t, 3J (H,H) = 10 Hz, 1 H), 0.99 (s, 18H). Methyl
3,5-bis{3’,5’-di(t-butyldiphenylsiloxy)benzyloxy}-benzoate.
Methyl
3,5-
dihydroxybenzoate (1.43 g, 8.53 mmol), 3,5-di(t-butyldiphenylsiloxy)benzyl alcohol (10.8 g, 17.5 mmol), and triphenylphosphine (6.71 g, 25.6 mmol) were dissolved in a mixture of 150 mL of CH2Cl2 and 10 mL of THF. The solution was cooled to 0 °C. Diethyl azodicarboxylate (4.1 mL, 26.0 mmol) was added slowly over a period of 30 min. It was stirred at rt for 12 h. The solvent was removed in vacuo, the residue partitioned between 1 L of ether and 100 mL of water, the organic phase washed with 1 M HCl (3x100 mL), water, saturated NaHCO3 (3x100 mL), water, and brine, dried over MgSO4, and the solvent evaporated. The crude product (yellow oil) was dissolved in the minimum amount CH2Cl2 and precipitated into methanol (1.2 L). The product was isolated as a white powder (8.32 g, 71 %). 1H NMR (500 MHz, CDCl3, 25 oC, TMS) δ 7.53 (d, 3J (H,H) = 13 Hz, 16 H), 7.35 (m, 8 H), 7.26 (dd, 3J (H,H) = 13 Hz, 13 Hz, 16 H), 7.07 (d, 3
J (H,H) = 4 Hz, 2 H), 6.40 (d, 3J (H,H) = 3 Hz, 5 H), 6.14 (dd, 3J (H,H) = 3 Hz, 3 Hz, 1
H), 4.67 (s, 4 H), 3.89 (s, 3 H), 0.99 (s, 36 H).
51
3,5-Bis{3’,5’-di(t-butyldiphenylsiloxy)benzyloxy}benzyl alcohol. Under inert gas atmosphere a suspension of lithium aluminum hydride (0.25 g, 6.51 mmol) in 50 mL of dry
THF
was
cooled
to
0
°C.
A
solution
of
methyl
3,5-bis{3’,5’-di(t-
butyldiphenylsiloxy)benzyloxy}-benzoate (8.47 g, 6.20 mmol) in 50 mL of dry THF was added slowly over a period of 45 min. The mixture was allowed to warm to rt and stirred for 1 h. (Careful monitoring by TLC is necessary to avoid cleavage of the silyl protecting groups.) It was quenched with saturated Na2SO4 and the THF was removed. The residue was taken up in ether and a filtration followed. Following Soxhlet extraction of the filter residue for 20 h, the organic phases were combined and washed with water and brine, dried over MgSO4, and the solvent evaporated. Chromatography (silica gel, 20 % ethyl acetate in hexanes) yielded the product as a white foam (6.7 g, 81 %). 1H NMR (500 MHz, CDCl3, 25 oC, TMS) δ 7.53 (d, 3J (H,H) = 13 Hz, 16 H), 7.35 (m, 8 H), 7.26 (dd, 3J (H,H) = 13 Hz, 13 Hz, 16 H), 6.40 (d, 3J (H,H) = 2 Hz, 4 H), 6.38 (d, 3J (H,H) = 2 Hz, 2 H), 6.18 (broad t, 1H), 6.13 (dd, 3J (H,H) = 2 Hz, 2 Hz, 2 H), 4.65 (s, 4 H), 4.53 (d, 3J (H,H) = 6 Hz, 2 H), 1.47 (t, 3J (H,H) = 6 Hz, 1 H), 0.99 (s, 36 H); 13C NMR (125 MHz, CDCl3) δ 159.89, 156.36, 142.99, 138.50, 135.41, 132.73, 129.72, 127.62, 111.81, 111.00, 105.53, 101.16, 69.45, 65.34, 26.51, 19.40; FTIR (KBr) 3071, 2930, 2858, 1591, 1450, 1169, 1114 cm-1; MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 1361.9 (calcd for C85H92O7Si4+Na+ 1360.9).
Preparation of 3,5-Di(tetrahydropyranyloxy)benzyl chloride: Methyl 3,5-di(tetrahydropyranyloxy)-benzoate.23 Methyl 3,5-dihydroxybenzoate was protected using standard conditions (98%). 1H NMR (500 MHz, CDCl3, 25 oC, TMS) δ 52
7.36 (d, 3J (H,H) = 5 Hz, 2 H), 6.96 (dd, 3J (H,H) = 5 Hz, 5 Hz, 1 H), 5.45 (dd, 3J (H,H) = 6 Hz, 3 Hz, 2 H), 3.90-3.86 (m, 2 H), 3.88 (s, 3 H), 3.61 (m, 2 H), 1.87-1.57 (m, 12 H). 3,5-Di(tetrahydropyranyloxy)benzyl alcohol.23 Under an argon atmosphere a flask was charged with methyl 3,5-di(tetrahydropyranyloxy)-benzoate (6.73 g, 20.0 mmol), potassium borohydride (0.65 g, 12.0 mmol), and lithium chloride (0.51 g, 12.0 mmol) in 30 mL of dry THF. It was refluxed for 60 h. (In TLC analysis UV-detection of the product is not recommended.) The mixture was allowed to cool to rt and then quenched with 12 mL of 2 M NaOH. It was stirred for another 2 h. The aqueous layer was extracted with CH2Cl2, the combined organic phases dried over MgSO4, and the solvent evaporated in vacuo to yield a colorless, viscous oil (4.67 g, 76 %). Due to observed migration of the protecting group to the free benzylic alcohol, the alcohol was immediately reacted further. 1
H NMR (300 MHz, CDCl3, 25 oC, TMS) δ 6.70 (broad s, 3 H), 5.41 (dd, 3J (H,H) = 6
Hz, 3 Hz, 2 H), 4.61 (s, 2 H), 3.90 (dt, 3J (H,H) = 9 Hz, 3 Hz, 2 H), 3.60 (m, 2 H), 2.021.56 (m, 12 H). 3,5-Di(tetrahydropyranyloxy)benzyl
chloride.
3,5-Di(tetrahydropyranyloxy)benzyl
alcohol (4.67 g, 15.1 mmol) was dissolved in the minimum amount of dry CH2Cl2. Triethylamine (2.54 mL, 18.2 mmol) was added and the solution was cooled to 0 ºC. A concentrated solution of p-toluenesulfonyl chloride (3.18 g, 16.7 mmol) in CH2Cl2 was added dropwise and the mixture was stirred at rt for 14 h. The solvent was evaporated and the residue chromatographed (silica gel, 20 % CH2Cl2 in hexanes). The compound was isolated as a colorless, viscous oil (5.00 g, 100 %). 1H NMR (300 MHz, CDCl3, 25 oC, TMS) δ 6.74 (broad s, 3 H), 5.41 (dd, 3J (H,H) = 6 Hz, 3 Hz, 2 H), 4.51 (s, 2 H), 3.90 (dt,
53
3
J (H,H) = 9 Hz, 3 Hz, 2 H), 3.61 (dt, 3J (H,H) = 9 Hz, 3 Hz, 2 H), 2.02-1.57 (m, 12 H);
13
C NMR (125 MHz, CDCl3) δ 158.27, 158.21; 139.26, 139.23; 109.92, 109.84; 105.27,
105.04; 96.45, 96.31; 61.99, 61.95; 46.32, 46.30; 30.29, 30.27; 25.17; 18.66, 18.63.24
General Procedure for Preparation of 2-Butyne-1,4-diethers 8a-d, 13: A mixture of sodium hydride (2.5 equiv.) in dry DMF was cooled to 0 °C. A solution of 2-butyne-1,4diol (1 equiv., 0.3 M) in dry DMF was added slowly and it was stirred at 0 °C for 1 h. Then, the appropriate benzylic halide (2.05 equiv., 0.3 M) dissolved in dry DMF was added. It was heated at 50 °C until full conversion (12-24 h). The solvent was removed in vacuo and the crude product purified using flash chromatography (silica gel, mixtures of hexanes/CH2Cl2).
8a:25 This was prepared as above from 2-butyne-1,4-diol and benzyl bromide (62 %). 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 7.41-7.31 (m, 10 H, Ph-H), 4.64 (s, 4 H, OCH2), 4.27 (s, 4 H, OCH2);
13
C NMR (125 MHz, CDCl3): δ 137.30, 128.37, 127.99,
127.81, 82.45 (C≡C), 71.54, 57.35.
8b: This was prepared as above from 2-butyne-1,4-diol and 7b (62 %). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 7.42-7.32 (m, 20 H, Ph-H), 6.63 (d, 4J (H,H) = 2 Hz, 4 H, Ar-o-H), 6.56 (t, 4J (H,H) = 2 Hz, 2 H, Ar-p-H), 5.02 (s, 8 H, OCH2), 4.56 (s, 4 H, OCH2), 4.23 (s, 4 H, OCH2);
13
C NMR (125 MHz, CDCl3): δ 160.05, 139.79, 136.79,
128.55, 127.96, 127.53, 106.81, 101.59, 82.50 (C≡C), 71.51, 70.04, 57.42; FTIR (KBr):
54
3032, 2868, 1613, 1454, 1381, 1170 cm-1; MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 713 (calcd for C46H42O6+Na+ 714); Anal. C: 80.30, H: 6.01 (calcd C: 79.98, H: 6.13).
8c: This was prepared as above from 2-butyne-1,4-diol and 7c (50 %). 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 7.42-7.31 (m, 40 H, Ph-H), 6.67 (d, 4J (H,H) = 2 Hz, 8 H, Ar-o-H), 6.62 (d, 4J (H,H) = 2 Hz, 4 H, Ar-o-H), 6.57 (t, 4J (H,H) = 2 Hz, 4 H, Ar-p-H), 6.53 (t, 4J (H,H) = 2 Hz, 2 H, Ar-p-H), 5.02 (s, 16 H, OCH2), 4.95 (s, 8 H, OCH2), 4.56 (s, 4 H, OCH2), 4.24 (s, 4 H, OCH2);
13
C NMR (125 MHz, CDCl3): δ 160.09, 159.93,
139.80, 139.21, 136.73, 128.54, 128.52, 127.94, 127.51, 106.80, 106.34, 101.52, 82.54 (C≡C), 71.47, 70.03, 69.88, 57.42; FTIR (KBr): 3031, 2870, 1596, 1449, 1158, 1055 cm-1; MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 1562 (calcd for C102H90O14+Na+ 1563); Anal. C: 79.36, H: 5.30 (calcd C: 79.56, H: 5.89).
8d: This was prepared as above from 2-butyne-1,4-diol and 7d (41 %). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 7.39-7.29 (m, 80 H, Ph-H), 6.65 (d, 4J (H,H) = 2 Hz, 16 H, Ar-o-H), 6.63 (d, 4J (H,H) = 2 Hz, 8 H, Ar-o-H), 6.60 (d, 4J (H,H) = 2 Hz, 4 H, Ar-o-H), 6.54 (t, 4J (H,H) = 2 Hz, 8 H, Ar-p-H), 6.51 (m, 4+2 H, Ar-p-H), 4.98 (s, 32 H, OCH2), 4.94 (s, 16 H, OCH2), 4.93 (s, 8 H, OCH2), 4.52 (s, 4 H, OCH2), 4.20 (s, 4 H, OCH2); 13C NMR (125 MHz, CDCl3): δ 160.12, 160.00, 159.97, 139.88, 139.22, 139.20, 136.76, 128.54, 127.95, 127.53, 106.80, 106.41, 106.37, 101.58, 101.55, 82.60 (C≡C), 71.47, 70.04, 69.93, 57.42; FTIR (KBr): 3031, 2932, 2870, 1605, 1452, 1377, 1167, 1057 cm-1;
55
MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 3257 (calcd for C214H186O30+Na+ 3261); Anal. C: 79.16, H: 6.00 (calcd C: 79.39, H: 5.79).
13: This was prepared as above from 2-butyne-1,4-diol and 3,5-di(tetrahydropyranyloxy)benzyl chloride (65 %). 1H NMR (300 MHz, CDCl3, 25 oC, TMS) δ 6.70 (broad s, 6H), 5.40 (dd, 3J (H,H) = 6 Hz, 3 Hz, 4 H), 4.53 (s, 4 H), 4.23 (s, 4 H), 3.90 (dt, 3J (H,H) = 9 Hz, 3 Hz, 4 H), 3.61 (m, 4 H), 2.01-1.56 (m, 24 H);
13
C NMR (125 MHz, CDCl3) δ
158.17, 158.11; 139.51, 139.49; 109.22, 109.16; 104.70, 104.48; 96.37, 96.22; 82.46 (C≡C); 71.53, 71.52; 61.98, 61.93; 57.43; 30.31, 30.28; 25.17; 18.72, 18.68;24 FTIR (film) 2953, 2864, 1601, 1454, 1346, 1153 cm-1; MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 688.9 (calcd for C38H50O10+Na+ 689.7); Anal. C: 68.89, H: 7.59 (calcd C: 68.45, H: 7.56).
Preparation of 1,4-Bis{2-(4’-t-butylphenylcarbonyloxy)-ethoxy}-2-butyne 18. A solution of 1,3-dicyclohexylcarbodiimide (0.52 g, 2.50 mmol) in 1 mL of CH2Cl2 was added to a solution of 4-t-butylbenzoic acid (0.374 g, 2.10 mmol), 1,4-bis(2hydroxyethoxy)-2-butyne (0.15 mL, 1.00 mmol), and 4-dimethylaminopyridinium ptoluenesulfonate (0.06g, 0.20 mmol) in 5 mL of CH2Cl2. The mixture was stirred for 24 h, filtered, and the solvent evaporated. Chromatography (silica gel, 3 % diethyl ether in CH2Cl2) gave 0.25 g of the desired product 18 (51 %) as well as 0.20 g of 1-{2-(4’-tbutylphenylcarbonyloxy)-ethoxy}-4-{2-(4’-t-butylphenylcarbonyloxy)-2-butyne. 18:
1
H
NMR (300 MHz, CDCl3, 25 oC, TMS) δ 7.99 (d, 3J (H,H) = 6 Hz, 4 H, Ar-H), 7.45 (d, 3J
56
(H,H) = 6 Hz, 4 H, Ar-H), 4.49-4.45 (m, 4 H, CH2O2C), 4.27 (s, 4 H, CH2C≡), 3.86-3.83 (m, 4 H, CH2O), 1.33 (s, 18 H, CH3); 13C NMR (125 MHz, CDCl3) δ 166.5, 156.7, 129.6, 127.2, 125.3, 82.3 (C≡C), 67.8, 63.7, 58.6, 35.0, 31.1; FTIR (film) 2963, 1721, 1610, 1275, 1117 cm-1; Anal. C: 71.87, H: 7.60 (calcd C: 72.85, H: 7.74).
General Procedure for Preparation of Benzene Core Dendrimers 9a-d, 14, 19: Under an argon atmosphere dicobalt octacarbonyl (5 mol%) was added to a solution of the appropriate 2-butyne-1,4-diether 8a-d, 13 (0.5 M) in dry toluene. It was refluxed until no further conversion could be reached (1-48 h). The solvent was removed in vacuo, and after standing in air for 1 h, the crude product was purified by flash chromatography (silica gel, mixtures of ether/CH2Cl2).
9a:26 This was prepared as above from 8a and purified by recrystallization from cyclohexane (83 %). Characterizational data agreed with the literature.26
9b: This was prepared as above from 8b (80 %). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 7.33-7.27 (m, 60 H, Ph-H), 6.57 (d, 4J (H,H) = 2 Hz, 12 H, Ar-o-H), 6.50 (t, 4J (H,H) = 2 Hz, 6 H, Ar-p-H), 4.90 (s, 24 H, OCH2), 4.56 (s, 12 H, OCH2), 4.32 (s, 12 H, OCH2); 13C NMR (125 MHz, CDCl3): δ 159.97, 140.69, 138.07, 136.82, 128.57, 128.46, 127.83, 127.50, 106.88, 101.37, 72.72, 69.93, 65.56; FTIR (KBr): 3031, 2870, 1595, 1451, 1376, 1159, 1060 cm-1; MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 2095 (calcd for C138H126O18+Na+ 2095); Anal. C: 80.08, H: 5.97 (calcd C: 79.98, H: 6.13). 57
9c: This was prepared as above from 8c (50 %). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 7.29-7.21 (m, 120 H, Ph-H), 6.55-6.53 (both d, 4J (H,H) = 2 Hz, 24+12 H, Ar-oH), 6.43 (t, 4J (H,H) = 2 Hz, 12+6 H, Ar-p-H), 4.81 (s, 48 H, OCH2), 4.74 (s, 24 H, OCH2), 4.56 (s, 12 H, OCH2), 4.29 (s, 12 H, OCH2);
13
C NMR (125 MHz, CDCl3): δ
160.01, 159.90, 140.78, 139.23, 138.16, 136.80, 128.44, 127.83, 127.49, 106.89, 106.34, 101.52, 72.88, 69.89, 69.80, 65.38; FTIR (film): 3030, 2925, 2868, 1596, 1451, 1376, 1296, 1158 cm-1; MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 4644 (calcd for C306H270O42+Na+ 4643); Anal. C: 79.77, H: 5.96 (calcd C: 79.56, H: 5.89).
9d: This was prepared as above from 8d (36 %). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 7.27-7.16 (m, 240 H, Ph-H), 6.53 (broad s, 24 H, Ar-o-H), 6.50 (broad s, 48+12 H, Ar-o-H and Ar-p-H), 6.40 (broad s, 24+6 H, Ar-p-H), 6.34 (broad s, 12 H, Ar-o-H), 4.76 (s, 96 H, OCH2), 4.66 (s, 24 H, OCH2), 4.63 (s, 48 H, OCH2), 4.57 (s, 12 H, OCH2), 4.28 (s, 12 H, OCH2);
13
C NMR (125 MHz, CDCl3): δ 159.95, 159.90, 159.85, 139.18,
136.75, 128.41, 127.80, 127.46, 107.61, 106.34, 106.29, 101.48, 69.81, 69.66, 67.63, 67.40; FTIR (film): 2920, 2871, 1595, 1451, 1374, 1296, 1160, 1055 cm-1; MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 9739 (calcd for C642H558O90+Na+ 9736); Anal. C: 77.56, H: 6.28 (calcd C: 79.39, H: 5.79).
14: This was synthesized as above from 13 (65 %). 1H NMR (500 MHz, CDCl3, 25 oC, TMS) δ 6.72 (dd, 3J (H,H) = 4 Hz, 2 Hz, 6 H), 6.67 (t, 3J (H,H) = 2 Hz, 12 H), 5.37 (m, 12 H), 4.51 (s, 12 H), 4.29 (s, 12 H), 3.87 (dt, 3J (H,H) = 9 Hz, 3 Hz, 12 H), 3.56 (m, 12 58
H), 1.99-1.53 (m, 72 H); 13C NMR (125 MHz, CDCl3) δ 158.02, 157.94; 140.48, 140.45; 137.94; 109.36, 109.30; 104.24, 103.99; 96.30, 96.12; 72.57; 65.38, 65.11; 61.85, 61.80; 30.24, 30.21; 25.10; 18.72, 18.67;24 MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z 2022.6 (calcd for C114H150O30+Na+ 2023.3); Anal. C: 68.46, H: 7.56 (calcd C: 68.45, H: 7.56).
19: This was synthesized as above from 18 (44 %). 1H NMR (300 MHz, CDCl3, 25 oC, TMS) δ 7.95 (d, 3J (H,H) = 6 Hz, 12 H, Ar-H), 7.41 (d, 3J (H,H) = 6 Hz, 12 H, Ar-H), 4.75 (s, 12 H, CH2Ph), 4.38 (t, 3J (H,H) = 5 Hz, 12 H, CH2O2C), 3.74 (t, 3J (H,H) = 5 Hz, 12 H, CH2O), 1.30 (s, 56 H, CH3);
13
C NMR (125 MHz, CDCl3) δ 166.4, 156.7, 137.7,
129.5, 127.2, 125.3, 68.5, 66.6, 63.8, 35.0, 31.0; FTIR (film) 2962, 1727, 1610, 1286, 1189, 1120 cm-1; MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z 1506.4 (calcd for C90H114O18+Na+ 1506.8); Anal. C: 72.72, H: 7.88 (calcd C: 72.85, H: 7.74).
Cyclotrimerization of 4 was carried out as above. After chromatography an inseparable mixture (∼1:1 by 1H NMR) of the two regioisomers 5 and 6 was obtained (34 %). Benzyl propargyl ether 427 was synthesized using standard PTC conditions (K2CO3, 18-crown6, acetone) in 80% yield. Characterizational data agreed with those published.27 Cyclotrimerization of 16 gave no reaction. Cyclotrimerization of 21 and 22 gave varying amounts of free phenol 20 but no trimerization product.
59
Preparation of 1,4-Bis{(2-benzyloxycarbonylethyl)-carboxy}-2-butyne 16: 1,4-Bis{(2-hydroxycarbonylethyl)-carboxy}-2-butyne. A solution of 2-butyne-1,4-diol (1.0 g, 11.6 mmol), succinic anhydride (2.44 g, 24.4 mmol), and 4-dimethylaminopyridine (0.14 g, 1.2 mmol) in 15 mL of acetonitrile was refluxed for 30 h. Complete conversion was indicated by 1H NMR. The solvent was evaporated and the residue recrystallized from water to afford 2.72 g of white crystals (82 %). 1H NMR (500 MHz, MeOH-d4, 25 oC) δ 4.75 (s, 4 H, CH2C≡), 2.61 (broad s, 8 H, CH2CH2); 13C NMR (125 MHz, CDCl3) δ 176.0, 173.5, 81.9, 53.1, 29.9, 29.7; FTIR (KBr): 3027, 1735, 1701, 1227, 1170 cm-1; Anal. C: 50.47, H: 5.06 (calcd C: 50.35, H: 4.93). 1,4-Bis{(2-chlorocarbonylethyl)-carboxy}-2-butyne. Oxalyl chloride (0.44 mL, 5 mmol) was added to a suspension of 1,4-bis{(2-hydroxycarbonylethyl)-carboxy}-2butyne (286 mg, 1.0 mmol) in 6 mL of CH2Cl2. Then one drop of DMF was added and the mixture was refluxed for 15 h. Evaporation of the solvent gave 320 mg of a yellow oil (99 %), which was immediately reacted further (see below). 1H NMR (500 MHz, CDCl3, 25 oC, TMS) δ 4.71 (s, 4 H, CH2C≡), 3.21 (t, 3J (H,H) = 7 Hz, 4 H, CH2COCl), 2.69 (t, 3J (H,H) = 7 Hz, 4 H, CH2CO2);
13
C NMR (125 MHz, CDCl3) δ 172.8, 170.0, 80.6, 52.5,
41.4, 28.9; FTIR (film): 1792, 1751, 1173 cm-1. 1,4-Bis{(2-benzyloxycarbonylethyl)-carboxy}-2-butyne 16. A solution of 1,4-bis{(2chlorocarbonylethyl)-carboxy}-2-butyne (320 mg, 1.0 mmol), benzyl alcohol (0.22 mL, 2.1 mmol), and pyridine (0.24 mL, 3.0 mmol) in 5 mL of CH2Cl2 was refluxed for 30 h. After evaporating the solvent, the residue was taken up in ether and extracted with water and brine, dried over MgSO4, and the solvent removed in vacuo to afford 396 mg of a yellow oil (86 %). 1H NMR (500 MHz, CDCl3, 25 oC, TMS) δ 7.37-7.33 (m, 10 H, Ar60
H), 5.14 (s, 4 H, PhCH2O), 4.71 (s, 4 H, CH2C≡), 2.69 (broad s, 8 H, CH2CH2); 13C NMR (125 MHz, CDCl3) δ 171.8, 171.4, 135.7, 128.5, 128.3, 128.2, 80.7, 66.6, 52.3, 29.0, 28.8; FTIR (film): 1751, 1160 cm-1; Anal. C: 65.82, H: 5.66 (calcd C: 66.94, H: 5.62).
Preparation of Zinc porphyrinyl alkynes 21 and 22: 5-(4-Hydroxyphenyl)-10,15,20-triphenylporphyrin 20.28 Pyrrole (6.95 mL, 100 mmol) was added to a solution of benzaldehyde (7.26 mL, 75 mmol) and p-anisaldehyde (3.04 mL, 25 mmol) in 60 mL of nitrobenzene and 140 mL of propionic acid. It was heated at 120 oC for 3 h and then allowed to stand overnight. All steps were carried out in the presence of air. After removing the solvent by vacuum distillation, the residue was dissolved in 60 mL of dry CH2Cl2 and added dropwise via an addition funnel to a solution of boron tribromide (.65 mL, 6.8 mmol) in 20 mL of CH2Cl2 at 0 oC. It was stirred overnight at rt, then water was added slowly followed by treatment with ammonia in methanol to adjust to basic pH. It was washed thoroughly with water, then brine, dried over MgSO4, and the solvent evaporated. Chromatography (silica gel, CH2Cl2) gave 1.00 g of 20 as a dark purple powder (6.3 %). The characterizational data agreed with the literature.28 Mono(zinc porphyrinyl)-alkyne 21. Diisopropyl azodicarboxylate (0.05 mL, 0.25 mmol) was added to a solution of 20 (100 mg, 0.16 mmol), 2-butyne-1,4-diol (68 mg, 0.79 mmol), and triphenylphosphine (62 mg, 0.24 mmol) in 4 mL of THF and it was stirred overnight. It was diluted with CH2Cl2, washed with water, brine, dried over MgSO4, and the solvent evaporated. Chromatography (silica gel, CH2Cl2) afforded 86 mg of a dark purple powder (77 %). 1H NMR (300 MHz, CDCl3, 25 oC, TMS) δ 8.88-8.84 61
(m, 8 H, β-H), 8.23-8.20 (m, 6 H, Ar-H), 8.12 (d, 3J (H,H) = 9 Hz, 2 H, O-Ar-H), 7.777.70 (m, 9 H, Ar-H), 7.31 (d, 3J (H,H) = 9 Hz, 2 H, O-Ar-H), 4.97 (s, 2 H, CH2C≡), 4.40 (s, 2 H, CH2C≡), -2.77 (broad s, 2 H, NH); MALDI-TOF MS (α-cyano-4hydroxycinnamic acid matrix): m/z 699.2 (calcd for C48H34N4O2+H+ 699.3). The corresponding zinc complex 21 was prepared by refluxing the free base porphyrin (1 equiv.) with zinc acetate (5 equiv.) in a mixture of CHCl3 and methanol. Metalation was monitored by UV/vis spectroscopy (Q-band region). After complete conversion (several hours), the solution was diluted with CH2Cl2, washed extensively with water, then brine, dried over MgSO4, and the solvent evaporated to give 21 in quantitative yield. The 1H NMR data are virtually identical to the free base porphyrin. MALDI-TOF MS (α-cyano4-hydroxycinnamic acid matrix): m/z 760.1 (calcd for C48H32N4O2Zn+ 760.2). Bis(zinc porphyrinyl)-alkyne 22. Diisopropyl azodicarboxylate (0.05 mL, 0.23 mmol) was added to a solution of 20 (100 mg, 0.16 mmol), 2-butyne-1,4-diol (6.5 mg, 0.79 mmol), and triphenylphosphine (59 mg, 0.075 mmol) in 3 mL of THF and it was stirred overnight. It was diluted with CH2Cl2, washed with water, brine, dried over MgSO4, and the solvent evaporated. Chromatography (silica gel, CH2Cl2) afforded 81 mg of a dark purple powder (82 %). 1H NMR (300 MHz, CDCl3, 25 oC, TMS) δ 8.87-8.78 (m, 16 H, β-H), 8.22-8.19 (m, 12 H, Ar-H), 8.08 (d, 3J (H,H) = 9 Hz, 4 H, O-Ar-H), 7.76-7.60 (m, 18 H, Ar-H), 7.41 (d, 3J (H,H) = 9 Hz, 4 H, O-Ar-H), 5.14 (s, 4 H, CH2C≡), -2.81 (broad s, 4 H, NH); MALDI-TOF MS (α-cyano-4-hydroxycinnamic acid matrix): m/z 1312.0 (calcd for C92H62N8O2+H+ 1312.6). The corresponding zinc complex 22 was prepared by refluxing the free base porphyrin (1 equiv.) with zinc acetate (5 equiv.) in a mixture of
62
CHCl3 and methanol. Metalation was monitored by UV/vis spectroscopy (Q-band region). After complete conversion (several hours), the solution was diluted with CH2Cl2, washed extensively with water, then brine, dried over MgSO4, and the solvent evaporated to give 22 in quantitative yield. The 1H NMR data are virtually identical to the free base porphyrin. MALDI-TOF MS (α-cyano-4-hydroxycinnamic acid matrix): m/z 1438.0 (calcd for C96H58N8O2Zn2+ 1438.3).
References 1. (a) Fréchet, J. M. J.; Jiang, Y.; Hawker, C. J.; Philippides, A. E. Preprints of the IUPAC International Symposium of Functional Polymers; The Polymer Society of Korea: Seoul, 1989, p 19. (b) Hawker, C. J.; Fréchet, J. M. J. J. Am. Chem. Soc. 1990, 112, 7638. (c) Hawker, C. J.; Fréchet, J. M. J. J. Chem. Soc., Chem. Commun. 1990, 1010. 2. (a) Newkome, G. R.; Moorefield, C. N.; Vögtle, F. Dendritic Molecules: Concepts, Synthesis, Perspectives; VCH: Weinheim, 1996. (b) Top. Curr. Chem. 1998, 197; 2000, 210; 2001, 212. (c) Bosman, A. W.; Jansen, H. M.; Meijer, E. W. Chem. Rev. 1999, 99, 1665. (d) Chow, H.-F.; Mong, T. K.-K.; Nongrum, M. F.; Wan, C.-W. Tetrahedron 1998, 54, 8543. (e) Fréchet, J. M. J.; Hawker, C. J. In Comprehensive Polymer Science, 2nd Suppl.; Aggarwal, S. L.; Russo, S., Eds.; Pergamon Press: Oxford, 1996, p 140. (f) Fréchet, J. M. J. Science, 1994, 263, 1710. (g) Tomalia, D. A.; Naylor, A. M.; Goddard, W. A., III Angew. Chem. Int. Ed. 1990, 29, 138. 3. Wooley, K. L.; Hawker, C. J.; Fréchet, J. M. J. Angew. Chem. Int. Ed. 1994, 33, 82.
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4. (a) For porhyrin cores, see: Pollak, K. W.; Sanford, E. M.; Fréchet, J. M. J. J. Mater. Chem. 1998, 8, 519. (b) for phthalocyanine cores, see: (b) Kimura, M.; Nakada, K.; Yamaguchi, Y.; Hanabusa, K.; Shirai, H.; Kobayashi, N. Chem. Commun. 1997, 1215. (c) Brewis, M.; Clarkson, G. J.; Holder, A. M.; McKeown, N. B. Chem. Commun. 1998, 696. c) Ng, A. C. H.; Li, X.-Y.; Ng, D. K. P. Macromolecules 1999, 32, 5292. d) Kimura, M.; Sugihara, Y.; Muto, T.; Hanabusa, K.; Shirai, H.; Kobayashi, N. Chem. Eur. J. 1999, 5, 3495. 5. (a) Schlüter, A. D.; Rabe, J. P. Angew. Chem. Int. Ed. 2000, 39, 864. (b) Schlüter, A. D. Top. Curr. Chem. 1998, 197, 165. 6. (a) Frühauf, H.-W. Chem. Rev. 1997, 97, 523. (b) Lautens, M.; Klute, W.; Tam, W. Chem. Rev. 1996, 96, 49. (c) Grotjahn, D. B. In Comprehensive Organometallic Chemistry II; Abel, E. A., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon:Oxford, 1995; Vol. 12, p 741. (d) Melikyan, G. G.; Nicholas, K. M. In Modern Acetylene Chemistry; Stang, P. J., Diederich, F., Eds.; VCH: Weinheim, 1995; p 99. (e) Schore, N. E. In Comprehensive Organic Synthesis; Trost, B. M., Flemming, I., Eds.; Pergamon: Oxford, 1991; Vol. 5, p 1129. 7. (a) Hübel, W. In Organic Synthesis via Metal Carbonyls; Wender, I.; Pino, P.; Eds.; Interscience: New York, 1968; Vol. 1, p 273. (b) Bowden, F. L.; Lever, A. P. B. Organomet. Chem. Rev., Sect. A 1968, 3, 227. (c) Hübel, W.; Hoogzand, C. Chem. Ber. 1960, 93, 103. (d) Kruerke, U.; Hübel, W. Chem. Ber. 1961, 94, 2829. (e) Mills, O. S.; Robinson, G. Proc. Chem. Soc. 1964, 187.
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8. A cobalt-catalyzed cyclotrimerization has recently been performed in aqueous solution: Sigman, M. S.; Fatland, A. W.; Eaton, B. E. J. Am. Chem. Soc. 1998, 120, 5130. 9. (a) Dickson, R. S.; Fraser, P. J. Adv. Organomet. Chem. 1974, 12, 323. (b) Schore, N. E.; LaBelle, B. E.; Knudsen, M. J.; Hope, H.; Xu, X.-J. Organomet. Chem. 1984, 272, 435. 10. For (Bu3P)2NiBr2 see: (a) Schönfelder, W.; Snatzke, G. Chem. Ber. 1980, 113, 1855. For [(η3-allyl)NiCl]2 see: (b) Reichsfel’d, V. O.; Lein, B. I.; Makovetskii, K. L. Dokl. Akad. Nauk SSSR 1970, 190, 125. 11. Duchêne, K. H.; Vögtle, F. Synthesis 1986, 659. 12. Kaufman, R. J.; Sidhu, R. S. J. Org. Chem. 1982, 47, 4941. 13. Olsman, H.; Graveland, A.; Arens, J. F. Recl. Trav. Chim. Pays-Bas 1964, 83, 301; 14. Balasubramanian, K. K.; Venugopalan, B. Tetrahedron Lett. 1973, 14, 2707. 15. (a) L’abbé, G.; Forier, B.; Dehaen, W. Chem. Commun. 1996, 2143. (b) Forier, B.; Dehaen, W. Tetrahedron 1999, 55, 9829. 16. (a) Tomoyose, Y.; Jiang, D.-L.; Jin, R.-H.; Aida, T.; Yamashita, T.; Horie, K. Macromolecules 1996, 29, 5236. (b) Jiang, D.-L.; Aida, T. Nature 1997, 388, 454. (c) Jiang, D.-L.; Aida, T. J. Am. Chem. Soc. 1998, 120, 10895. 17. de Gennes, P.-G.; Hervet, H. J. Phys. Lett. 1983, 44, L 351. 18. Lescanec, R. L.; Muthukumar, M. Macromolecules 1990, 23, 2280. 19. (a) Murat, M.; Grest, G. S.
Macromolecules 1996, 29, 1278. (b) Boris, D.;
Rubinstein, M. Macromolecules 1996, 29, 7251. 20. Kochi, J.; Hammond, G. S. J. Am. Chem. Soc. 1953, 75, 3443. 65
21. Fletcher, J. T.; Therien, M. J. J. Am. Chem. Soc. 2000, 122, 12393. 22. Biemans, H. A. M.; Rowan, A. E.; Verhoeven, A.; Vanoppen, P.; Latterini, L.; Foekema, J.; Schenning, A. P. H. J.; Meijer, E. W.; De Schryver, F. C.; Nolte, R. J. M. J. Am. Chem. Soc. 1998, 120, 11054. 23. Reimann, E. Liebigs Ann. Chem. 1971, 750, 109. 24. Please note that the carbon signals corresponding to the THP-diastereomers are separated by a semicolon. 25. Arai, A.; Ichikizaki, I. Bull. Chem. Soc. Jpn. 1961, 34, 1571. 26. Hardy, A. D. U.; MacNicol, D. D.; Wilson, D. R. J. Chem. Soc., Perkin Trans. II 1979, 1011. 27. Ren, X.-F.; Turos, E.; Lake, C. H.; Churchill, M. R. J. Org. Chem. 1995, 60, 6478. 28. Monti, D.; Venanzi, M.; Mancini, G.; Marotti, F.; La Monica, L.; Boschi, T. Eur. J. Org. Chem. 1999, 1901.
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Chapter 3:
Site Isolation in Porphyrin Core Dendrimers – The Effect of Core Size and Structure
Abstract The photophysical and hydrodynamic properties of dendrimers having porphyrin and metalloporphyrin cores have been studied. Fluorescence anisotropy decays have been used to deduce information about the intrinsic viscosity and hydrodynamic radii of the macromolecules. The results have been correlated to previously reported viscometry measurements and show a clear dependence of the structural collapse of the dendritic structure, which is directly related to site isolation, on the core size. This chapter has been reproduced in part with permission from Macromolecules 2000, 33, 2967-2973. Copyright 2000 American Chemical Society.
67
Introduction The encapsulation of active core functionalities within dendritic backbones1 has been thoroughly investigated in recent years.2 It could be shown that the dendrimer shell profoundly affects the core properties demonstrating the concept of site isolation. The application of such functional dendrimers3 spans a wide range from serving as biological mimics of enzyme functions to the design of nanoscale molecular devices. In particular, porphyrin core dendrimers4-7 have been studied extensively due to their potential as hemeprotein mimics for electron transport, dioxygen binding, and oxidation catalysis. Several different dendritic backbones, such as polyether,4 polyamide,5 polyester6, and poly(phenylene)7 dendrimers, have been used to encapsulate porphyrin cores and their respective metal complexes. Due to the inherent photophysical and electrochemical characteristics of the investigated compounds, much information about core isolation has been gained using either UV-titration,4d,6c fluorescence quenching,4a,c,e,h,5f,g or cyclovoltammetry experiments.4h,5a-c,e In general, a generation dependence of site isolation, i.e. increasing core encapsulation with increasing generation number, was observed. However, no detailed information about the influence of the core structure on the overall molecular structure in solution and therefore the degree of site isolation is available. Following Tomalia’s early studies,1g,8 theoretical models have been proposed to account for the properties of dendritic architectures. Murat and Grest9 as well as Boris and Rubinstein10 have shown the internal density profile to decrease monotonically from the center of the molecule in agreement with earlier results obtained by Lescanec and
68
Muthukumar.11 These theoretical predictions of a maximum of the intrinsic viscosity upon increasing the generation were experimentally supported by Mourey et al.12 We describe the effects of generation number and solvent on the hydrodynamic and photophysical properties of two different series of porphyrin core dendrimers in solution. In particular, time-resolved fluorescence anisotropy experiments were used to determine molecular properties, such as the hydrodynamic volume (Vh) and radius (rh) as well as the intrinsic viscosity (η).13 The correlation between hydrodynamic and photophysical properties offers the unique opportunity to gain further insight into the dendritic structure and its dependence on the nature of the core and dendrons as well as the solvent.
Results and Discussion Synthesis. The porphyrin and metalloporphyrin core dendrimer series were prepared by attachment of poly(benzyl ether) type dendritic bromides14 to the respective phenolic cores via a Williamson ether synthesis (Scheme 3.1). For preparation of the dendrons see Chapter 2 (Scheme 2.5). The cores 1-3 were synthesized by Adler-Longo type condensation of the respective aromatic aldehydes with pyrrole,15 followed by deprotection of the phenolic groups (masked as methyl ethers) and metalation, if necessary. Not unexpectedly, the yields generally decreased with increasing generation and larger excess of the dendrons had to be used in order to drive the reactions to completion. The structures of the different series, i.e. dendritic zinc and manganese porphyrins 4a-d, 5b-d and dendritic free base porphyrins 6b-d are shown in Scheme 3.2 and Scheme 3.3. 69
Scheme 3.1 HO
HO
OH
N
RO
N M N
N
HO
HO
R-Br
OH
RO
K2CO3, 18-crown-6
N
∆ (acetone)
N
O
OH
Bn
OR
OR
4a-d (M=ZnII) 5b-d (M=MnIIICl)
Bn
n [G-n] (n = 1 - 3) a: R = Bn b: R = Bn2[G-1] c: R = Bn4[G-2] d: R = Bn8[G-3]
OH
N
RO
R= O
OR
N M
RO
OH
1 (M=ZnII) 2 (M=MnIIICl)
OR
OR
R-Br N
HN
HO
OH N
NH
K2CO3, 18-crown-6 ∆ (acetone)
N
HN
NH
N
RO
OR
OR
OH
3
6b-d
The manganese porphyrin series 5b-d was initially prepared to design oxygenation catalysts mimicking Cytochrome P450.16 In addition, the paramagnetic metal center constitutes a sensitive probe for site isolation using EPR techniques. However, it was found that compounds 5b-d were rather unstable and their decomposition has been ascribed to µ-oxo dimer formation and self-destruction by C-H activation of the benzylic positions of the dendrimer backbone. This finding clearly demonstrates the need for oxidatively robust dendritic backbones, such as polyester dendrimers,6a,b for the design of Cytochrome P450 mimics. 70
Scheme 3.2
O
O
O
O
O
O
O
O O
O
O
O
O
O O
O
O
O
O
O
O
N
O
N
O
O
O
O
N
O
M
N
O
O
O
N
O
O
O
M N
N
O
O
O
O
O
O
N
O
O
O
O
O
O O
O
O
O
O
O
O
4a (M=ZnII)
O
O
O O
O
O
O
O O
O
OO O
O
O
O
O
4c (M=ZnII) 5c (M=MnIIICl)
OO
O
O
O O
O
O O O
O
O
O
O
O
O O
O
O
O
OO
O
O
O O
O
O O
O
O
O
O
O O
O
O
OO O
O
O O
O O
O
O
N
O
N
N
O
O
O
O
N
O
O
O
O
O
O
N
O
O
O
N
O
O
O
O
O O
N
O
O
O
O
O
O
O
O OO
O O
O
O O
O
O
O
O
O
O
O
O O
O
O
O O O OO
O O
O O
O
4b (M=ZnII) 5b (M=MnIIICl)
O O
O
O O
O O
M
O
N
O
O
O
M O
O
O O O
O
O
O
O O
O O
O
OO
O O OO
OO
O
O
OO
4d (M=ZnII) 5d (M=MnIIICl)
In addition to the preparation of these benzyl-terminated poly(benzyl ether) dendrimers, attempts were made to introduce peripheral functionality in order to tune the solubility behavior of the dendritic superstructures. However, due to solubility problems the synthesis of higher generation 4-(methylcarboxy)benzyl-terminated porphyrin core 71
Scheme 3.3
O
O
O
O
O
O
O
O
O
O
O
O
O N
O
O
O N
HN
O
O
O
O
O
O
O
N
NH
HN
N
NH O
O
O
O
O
O
O
O
O
6b O
O
O
O
O
O
O
O
O
6c
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O O O
O
O
O
O
N
HN
NH
N
O
O
O
O
O
O
O
O
O
O
O
O
O
O O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O O
6d
O O
O
poly(benzyl ether) dendrimers4c,e failed. Hence, other backbones (aliphatic polyesters) were used to introduce peripheral functionality as described in Chapter 5. This is crucial for the design of catalysts since a polarity difference between interior and surface is needed to drive the reaction. 72
5b 3216 (3215)
5c 6609 (6611)
5d 13408 (13403)
4000
6000
8000
10000
12000
14000
mass (m/z)
Figure 3.1. MALDI-TOF mass spectra of compounds 5b-d (as MnIIIporphyrin+).
Absorption and Emission Properties. The UV-vis absorption spectra of compounds 4a-d and 6b-d (Figure 3.2) are are similar to the ones obtained for zinc tetraphenylporphyrin (ZnTPP) and tetraphenylporphyrin (TPP), respectively.17 In the two different solvents, tetrahydrofuran (THF) and dimethylformamide (DMF), both Soret and Q bands do not shift upon increasing the concentration up to 10-6 M indicating the absence of intermolecular aggregation processes in the ground state. This finding was confirmed applying a methodology developed by Pasternack and coworkers18 allowing for the determination of porphyrin aggregates. As the generation number of 4 increases (Figure 2), a small red shift of the Soret band is observed while the Q bands remain unchanged. In contrast, no shift is observed for 6b-d. The same spectral effect was observed for similar compounds by Aida and coworkers, who suggested such red shift to be associated with the encapsulation degree of the chromophore into the dendrimer framework.4d Therefore, this small bathochromic shift of the Soret band in 4a-d is an
73
indication of weak interactions between the core and the branches, which could affect the photophysical properties of the porphyrin moiety. 1
G=1 G=2
1
A
normalized absorbance
G=3 G=4
555
G=1 G=2
B
G=3
Q bands
Q bands
517 553
595
595
0
653
0 350
400
450
500
550
600
650
700
wavelength(nm)
350
400
450
500
550
600
650
700
wavelength (nm)
Figure 3.2. Absorption spectra of (a) compounds 4a-d and (b) compounds 6b-d in THF. The spectra are normalized relative to the absorption maxima.
The variation profile of the Soret band in compounds 4a-d is similar in both solvents (THF and DMF) and the difference in energy between dendrimers of the same generation in different solvents remains approximately constant (≈ 0.015 eV). An analysis of the maxima of the excitation spectra in DMF and THF as a function of generation is depicted in Figure 3.3. These results indicate that the observed behavior is not caused by a solvent effect but rather due to enhanced interactions between the core and the dendrons as a function of generation. In addition, we suggest that the absence of a red shift starting from the third generation is caused by an increased steric crowding around the porphyrin ring, disabling additional interactions between chromophore and dendrons. Physical measurements on related higher generation dendrimers (G ≥ 3) with a compact structure showing encapsulation of the core19 support our rationalization.
74
430
429
λ max
428
427
426
425
1
2
3
4
generation
Figure 3.3. Dependence of the Soret band maxima on generation number for compounds 4a-d in DMF (%) and in THF (!).
The emission and excitation spectra of the compounds are reported in Figure 3.4. A similar Stokes shift (≈ 10 nm) is obtained for all generations. The Q emission bands do not shift and their intensity ratio is constant for all generations in agreement with the absorption spectra where the Q bands are unchanged.
normalized intensity
1.0
1.0
(a)
0.8
0.8
0.6
0.6
0.4
0.4
0.2
0.2
Excitation
Emission
Excitation 0.0 500
550
600
650
(b)
700
750
wavelength (nm)
0.0 450
500
550
Emission 600
650
700
750
wavelength (nm)
Figure 3.4. Excitation and emission spectra of (a) compound 4b and (b) compounds 6b in THF. The spectra are normalized for comparison.
The fluorescence quantum yield (Φf) obtained in different solvents does not change as a function of generation. The Φf values measured for 4a-d and 6b-d are 75
identical to those determined for ZnTPP (Φf = 0.033)20 and TPP (Φf = 0.11),21 respectively. This result suggests little influence of the dendrons on the non-radiative and radiative deactivation processes of the porphyrin core.
Fluorescence Depolarization and Hydrodynamic Properties. The hydrodynamic properties and the anisotropy parameters obtained from global analysis of three decays at different angles of the emission polarizer are shown in Tables 3.1 and 3.2. All fluorescence decays show a monoexponential profile in both dendrimer series. The values of decay time (τ) do not change in 4a-d as well as in 6b-d. The observed small variation (1.6 - 1.7 ns) of the decay time for 4a-d is within the experimental error (10%). The anisotropy decays of all generations are fitted to a single-exponential model. The β-values obtained for all generations are similar to the values of the limiting anisotropy (r0) of ZnTPP and TPP22 (β = 0.11). In both dendritic systems, φ increases as the dendrimer becomes larger as predicted on the basis of the Stokes-Einstein-Debye relation
φ = Vhη / kT
(1)
where Vh is the hydrodynamic volume, η the viscosity of the solvent, k the Boltzmann constant, and T the absolute temperature. Structural changes are deduced from changes in the free volume, Vfree (the difference between van der Waals volume, Vvw and hydrodynamic volume, Vh), where the van der Waals volumes are calculated from Edward's increments.23 The values for Vfree show a collapse of the structure between the
76
third and fourth generation for 4a-d in both solvents in contrast to 5b-d, where no maximum is observed. Table 3.1.
Hydrodynamic properties and parameters from global analysis of the fluorescence anisotropy decays of compounds 4a-d and 6b-d in THF at room temperature. The values of τ, β and φ are freely adjustable. τ
β
(ns)
φ
2
χ
(ns)
MW
Vh
Vvw
(g/mol)
(Å3)
(Å3)
(Å3)
ρ
[η]
(g/mL)
(dL/g)
Vfree
6b
10.4
0.05
0.69
1.15
1888
4514
1660
2854
0.695
0.036
6c
10.5
0.05
1.38
1.01
3586
9051
3148
5903
0.658
0.038
6d
10.7
0.06
2.88
1.03
6982
18890
6124
12766
0.614
0.041
4a
1.54
0.10
0.39
1.08
1527
2558
1293
1265
0.991
0.025
4b
1.61
0.10
1.16
1.20
3221
7608
2781
4827
0.703
0.035
4c
1.68
0.10
2.43
1.12
6621
15938
5757
10181
0.690
0.036
4d
1.68
0.10
3.23
1.20
13413
21185
11709
9476
1.051
0.024
Table 3.2.
Hydrodynamic properties and parameters from global analysis of the fluorescence anisotropy decays of compounds 4a-d and 6b-d in DMF at room temperature. The values of τ, β and φ are freely adjustable. τ
β
(ns)
φ
2
χ
(ns)
MW
Vh
Vvw
(g/mol)
(Å3)
(Å3)
(Å3)
ρ
[η]
(g/mL)
(dL/g)
Vfree
6b
10.3
0.08
0.99
1.01
1888
4041
1660
2381
0.776
0.032
6c
10.4
0.07
1.99
1.10
3586
8122
3148
4974
0.733
0.034
6d
10.3
0.07
4.29
1.07
6982
17510
6124
11386
0.662
0.038
4a
1.64
0.11
0.74
1.13
1527
3020
1293
1727
0.840
0.030
4b
1.72
0.12
2.13
1.12
3221
8694
2781
5913
0.615
0.041
4c
1.76
0.09
3.49
1.01
6621
14245
5757
8488
0.772
0.032
4d
1.77
0.09
3.63
1.03
13413
14816
11709
3107
1.503
0.017
77
The intrinsic viscosity [η] of a dendrimer can be expressed through its hydrodynamic volume, Vh,17 as
[η] = 2.5Na(Vh/MW)
(2)
where Na is the Avogadro’s number and MW is the molecular weight. As shown in Figure 3.5, the intrinsic viscosity for 4a-d dendrimers passes through a maximum as a function of generation number in both solvents. These results are in agreement with the predictions of Tomalia et al.1g,8 and the simulations of Lescanec and Muthukumar11 that predict a maximum in intrinsic viscosity as a function of generation. In addition, the resulting curve profile agrees well with that obtained experimentally by Mourey et al.12 using similar polyether dendrimers. -3.0 -3.1 -3.2
-1
Ln [[η] (dL g )]
-3.3 -3.4 -3.5 -3.6 -3.7 -3.8 -3.9 -4.0 -4.1 -4.2
1
2
3
4
generation Figure 3.5. Logarithm of intrinsic viscosity as a function of generation number: compounds 4a-d in THF (!) and in DMF (%), as well as compounds 6b-d in THF (#) and in DMF (&).
78
In contrast to 4a-d, the values of intrinsic viscosity obtained for 6b-d (Figure 3.5) show only a small variation in both solvents. This effect is due to the linear dependence of Vh on molecular weight (MW) (Vh ∝ MW1.10 in DMF and Vh ∝ MW1.11 in THF), which is unusual for this class of dendrimers. The structures of 6b-d do not collapse within the investigated range of generations and their free volume increases linearly with generation. The effect of the solvent on hydrodynamic radius (rh) of 4a-d and 6b-d is shown in Figure 3.6. In both solvents the hydrodynamic radius (rh= Vh1/3) of zinc porphyrin core dendrimers up to the third generation (4a-c) has a similar value relative to that of the extended structure in the gas phase (where interactions among branches and solvent effects are excluded and rh ∝ G).9 However, for the fourth generation (4d), the structure collapses and the hydrodynamic radius decreases remarkably (a decrease of 2.9 Å in THF and of 6.0 Å in DMF). Interestingly, the structures of 6b-d are not fully extended compared to their gas phase radii indicating a more dense structure than for 4a-d. 34
34 32
rh(Å)
30
(a)
32 30
28
28
26
26
24
24
22
22
20
20
18
18
16
16
14
14
12
12
10
10
8
(b)
8
1
2
3
4
1
generation
2
3
generation
Figure 3.6. Hydrodynamic radius as a function of generation number: (a) compounds 4a-d in the gas phase (!), in THF (#), and in DMF (%), as well as compounds 6b-d in the gas phase (!), in THF (#), and in DMF (%).
79
The differences observed for 4a-d and 6b-d can be explained considering their different molecular structure. The main structural difference arises from the core size, thus, having a profound effect on the resulting dendrimer architecture. As can be seen in Figure 3.7, the core in 6b-d is extended due to the insertion of an additional parasubstituted phenyl ring separating the dendrons from the core. The larger core size of 6b-d leads to an increased distance between the dendrons minimizing steric hindrance as compared to 4a-d where the dendrons are linked directly to the porphyrin core. As a result, the branches in 6b-d are more flexible and able to adopt more conformations. This enhancement of flexibility results in a less extended structure compared to 4a-d and allowing the terminal groups to sample more conformational space. This structural effect would decrease the hydrodynamic volume of the dendrimer in comparison to theoretical, fully extended structures. Relating the obtained results to work on similar Fréchet-type dendrimers using a different experimental setup employing size exclusion chromatography coupled to differential viscometry,12 we conclude that given the same dendritic backbone, the point of structural collapse can be correlated to the size of the dendrimer core. Investigating 1,1,1-tris(4-hydroxyphenyl)ethane-cored dendrimers, Mourey and coworkers had found a viscosity maximum at the third generation. Consequently, we suggest that with increasing core size, i.e. zinc porphyrin smaller than 1,1,1-tris(4-hydroxyphenyl)ethane smaller than tetra(4-hydroxyphenyl)porphyrin, the maximum of the intrinsic viscosity is shifted towards higher generation (Figure 3.7). In addition to the core size, the rigidity of the core and the number of the dendritic substituents will certainly influence the hydrodynamic properties, but such contributions cannot be deconvoluted from the current data. 80
G O
G G
N N
Zn
N N
G G
G
O
G
G
N NH
O
HN N
G O
O O
G O
G
(a)
(b)
(c)
Figure 3.7. Structural comparison of the investigated cores and their sizes: (a) zinc porphyrin core, (b) 1,1,1-tris-(4-hydroxyphenyl)ethane core, and (c) tetra(4-hydroxyphenyl)porphyrin core (G=dendron). Core geometries were optimized using molecular mechanics.
Conclusion Polyarylether dendrimers with zinc porphyrin and TPP cores do not aggregate in solution and exhibit intramolecular interactions between the porphyrin unit and the dendrons in the ground state. The value of intrinsic viscosity for 4a-d passes through a maximum as a function of generation in qualitative agreement with other experimental12,13 and theoretical studies.8-11 In contrast to the zinc series, 6b-d exhibits an intrinsic viscosity approximately constant with generation in the investigated range (n=1-3). The different behavior is attributed to structural differences in the two dendrimer series studied caused by an additional phenyl group further separating the dendrons and the core moiety. This extra spacer increases the distance between the dendrons 81
minimizing steric hindrance and leading to an enhanced flexibility. Therefore, the terminal groups sample more conformational space and the hydrodynamic volume decreases compared to the theoretical, fully extended structures in the gas phase. Comparison with viscosity measurements12 that complement our experimental approach shows the important contribution of core size to the hydrodynamic properties of dendritic structures and therefore site isolation in general. These findings suggest that in order to facilitate site isolation, the number of points for dendron attachment as well as their orientation with regard to the core have to be optimized, illustrating the importance of rational core design.
Experimental General Methods: All reagents were used as received and without further purification, unless otherwise noted. Poly(benzyl ether) type dendritic bromides14 of generation 1-3 were synthesized as described in detail in Chapter 2. The metalloporphyrin cores 1 and 2 were
prepared
from
the
parent
free
base
porphyrin
5,10,15,20-tetrakis(3,5-
dihydroxyphenyl)porphyrin via standard metalation procedures using either zinc(II) acetate or manganese(II) acetate. In the case of manganese insertion, treatment with diluted HCl afforded the manganese(III) chloride species.24 The free base porphyrins 5,10,15,20-tetrakis(3,5-dihydroxyphenyl)porphyrin25 and 5,10,15,20-tetrakis-(4-hydroxyphenyl)porphyrin 3 were synthesized in a two step sequence involving Adler-Longo-type condensation15 of pyrrole with 3,5-dimethoxybenzaldehyde and p-anisaldehyde, respectively, followed by demethylation using either boron tribromide or pyridinium chloride. Overall yields were 30-45 %. Column chromatography was carried out with 82
Merck silica gel for flash columns, 230-400 mesh. NMR spectra were recorded on Bruker AMX-300 (300 MHz), Bruker AM-400 (400 MHz), or Bruker DRX-500 (500 MHz) instruments with TMS or solvent carbon signal as the standards. Matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was performed on a PerSeptive Biosystems Voyager-DE spectrometer equipped with a nitrogen laser (337 nm) in delayed extraction mode and an acceleration voltage of 20 keV. Samples were prepared using a 1:20 ratio of analyte (5 mg/mL in THF) to matrix solution (trans-3indoleacrylic acid, 10 mg/mL in THF). Elemental analyses were performed by MHW laboratories. Spectroscopy. All solvents used were of spectroscopic grade and stored over 4 Å molecular sieves. The optical density of the investigated solutions was always less than 0.1 to avoid spectral distortion due to the inner-filter effect. Time-resolved fluorescence measurements were performed on samples degassed by several freeze-pump-thaw cycles. Electronic absorption spectra were recorded at 20 ± 1 °C with a Perkin–Elmer Lambda 6 UV-Visible Spectrophotometer. Steady state fluorescence spectra at room temperature were measured with a SPEX Fluorolog 212. The polarized emission decays were obtained by a single-photon-timing-technique.26 The compounds were excited at 425 nm (for 4a-d) and at 420 nm (for 6b-d) using the output of a titanium-sapphire laser pumped by a beamlocked argon ion laser with repetition frequency of the excitation pulses of 400 kHz. TBO (bis-[1-octadecyl-benzoxazol-2-]-trimethine perchlorate) in methanol (τ = 0.14 ns) and coumarin 153 in ethanol (τ = 4.6 ns) were used as reference compounds. The number of counts in the peak channel was approximately 104. Time increments of 45 and 20 ps/channel were used. The decay traces were collected at three different orientations of 83
the emission polarizer (0º, 54.7º and 90º). The decay parameters were recovered using a global analysis-fitting program. The quantum yield of all compounds was determined from the equation
F A Φ = sample ref Φ ref Fref Asample
2 nsample 2 n ref
where Fsample and Fref are the measured fluorescence (area under the fluorescence spectra) of the sample and the reference respectively, Asample and Aref are the absorbances of the sample and the reference respectively at the same excitation wavelength, Φ ref is the quantum yield of the reference and n is the refractive index. 5,10,15,20Tetrakis(phenyl)porphyrin in propanol was used as a reference (Φf = 0.075)27 in our measurements. Data Analysis. The analysis of the fluorescence decays for compounds 4a-d and 6b-d was carried out at a detection wavelength of 600 nm to eliminate any contribution from traces of free base porphyrin in the zinc series (4a-d). The fluorescence intensity decays, i(θ,τ), were simultaneously analyzed using a global analysis-fitting program according to
(
)
m
(
)
I(θ , τ ) = [κ(θ ) 3]α exp(− t τ )1 + 3 cos 2 θ − 1 ∑ β1 exp − t φ j J =1 where t represents the fluorescence decay time and φj the rotational correlation times of the fluorophore. κ(θ) is a generally time independent matching factor. β is a preexponential factor, which is characteristic for the fluorophore, related to the transition dipole moment of absorption and emission, and independent of the solvent. The program uses reference convolution and reference lifetime, τref, which is in all cases freely
84
adjustable. The equations and details of the global analysis program have been reported previously.28 All global analyses were performed on an IBM RISC 6150-125 computer.
General Procedure for the Preparation of Dendritic Zinc Porphyrins 4a-d:4g,h A mixture of zinc 5,10,15,20-tetrakis(3,5-dihydroxyphenyl)porphyrin 1 (1 equiv., 2.5 mM, the appropriate poly(benzyl ether) type dendritic bromide (9.6 equiv.), K2CO3 (16 equiv.), and 18-crown-6 (1.6 equiv.) in dry acetone was refluxed for 4-8 d. (To drive the reaction to completion the addition of more dendritic bromide was sometimes necessary.) The solvent was evaporated and the residue taken up in CH2Cl2. The organic phase was washed with water and brine, dried over MgSO4, and the solvent removed in vacuo. Chromatography (silica gel, linear gradient from CH2Cl2 / hexanes to CH2Cl2) afforded the desired products as purple glasses.
4a:4g,h This was prepared as above from 1 and benzyl bromide (95 %). 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 8.98 (broad s, 8 H, β-H), 7.48 (d, 4J (H,H) = 3 Hz, 8 H, Aro,o’-H), 7.35 (m, 40 H, Ph-H), 7.02 (t, 4J (H,H) = 3 Hz, 4 H, Ar-p-H), 5.18 (s, 16 H, CH2O);
13
C NMR (125 MHz, CDCl3) δ 157.8, 149.9, 144.6, 136.7, 132.0, 128.6, 128.0,
127.6, 120.7, 115.1, 96.7; MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 1538 (calcd for C100H76N4O8Zn+ 1527); Anal. C: 78.60, H: 5.05, N: 3.54 (calcd C: 78.65, H: 5.02, N: 3.67); UV/vis (CHCl3) λmax (ε) 428 nm (568000), 560 nm (22000), 600 nm (7000).
85
4b:4g,h This was prepared as above from 1 and first generation dendritic bromide (71 %). 1
H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 9.18 (broad s, 8 H, β-H), 7.48 (d, 4J (H,H) =
3 Hz, 8 H, Ar-o,o’-H), 7.33 (m, 80 H, Ph-H), 7.03 (t, 4J (H,H) = 3 Hz, 4 H, Ar-p-H), 6.73 (d, 4J (H,H) = 2 Hz, 16 H, Ar-o,o’-H), 6.56 (t, 4J (H,H) = 2 Hz, 8 H, Ar-p-H), 5.06 (s, 16 H, CH2O), 4.96 (s, 32 H, CH2O);
13
C NMR (125 MHz, CDCl3) δ 160.1, 157.7, 149.9,
144.8, 139.1, 136.6, 132.1, 128.5, 127.9, 127.4, 120.7, 115.0, 106.4, 101.6, 96.7, 70.0; MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 3228 (calcd for C212H172N4O24Zn+ 3225); Anal. C: 79.06, H: 5.75, N: 1.62 (calcd C: 78.95, H: 5.38, N: 1.74); UV/vis (CHCl3) λmax (ε) 428 nm (498000), 560 nm (20000), 600 nm (7000).
4c:4g,h This was prepared as above from 1 and second generation dendritic bromide (68 %). 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 8.96 (broad s, 8 H, β-H), 7.48 (d, 4J (H,H) = 3 Hz, 8 H, Ar-o,o’-H), 7.17 (m, 160 H, Ph-H), 7.03 (t, 4J (H,H) = 3 Hz, 4 H, Arp-H), 6.67 (d, 4J (H,H) = 2 Hz, 16 H, Ar-o,o’-H), 6.53 (d, 4J (H,H) = 2 Hz, 32 H, Ar-o,o’H), 6.43 (t, 4J (H,H) = 2 Hz, 8 H, Ar-p-H), 6. 93 (t, 4J (H,H) = 2 Hz, 16 H, Ar-p-H), 5.06 (s, 16 H, CH2O), 4.83 (s, 32 H, CH2O), 4.78 (s, 64 H, CH2O);
13
C NMR (125 MHz,
CDCl3) δ 160.1, 160.0, 157.7, 149.8, 139.2, 139.2, 136.6, 128.4, 127.8, 127.4, 120.7, 106.6, 106.2, 101.6, 101.5, 96.7, 69.9; MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 6630 (calcd for C436H364N4O56Zn+ 6621); Anal. C: 78.98, H: 5.96, N: 0.50 (calcd C: 79.09, H: 5.54, N: 0.85); UV/vis (CHCl3) λmax (ε) 428 nm (534000), 560 nm (20000), 600 nm (7000).
86
4d:4g,h This was prepared as above from 1 and third generation dendritic bromide (20 %). 1
H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 9.00 (broad s, 8 H, β-H), 7.48 (d, 4J (H,H) =
3 Hz, 8 H, Ar-o,o’-H), 7.19 (m, 320 H, Ph-H), 6.67 (s, 4 H, Ar-H), 6.52–6.38 (m, 168 H, Ar-H), 4.91 (s, 16 H, CH2O), 4.75–4.69 (m, 224 H, CH2O); 13C NMR (125 MHz, CDCl3) δ 160.0, 159.9, 159.8, 157.8, 149.7, 139.2, 139.1, 136.6, 132.1, 128.4, 127.8, 127.4, 106.2, 101.4, 69.8; MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 13437 (calcd for C884H748N4O120Zn+ 13413); Anal. C: 79.24, H: 5.79, N: 0.59 (calcd C: 79.16, H: 5.62, N: 0.42); UV/vis (CHCl3) λmax (ε) 430 nm (463000), 560 nm (21000), 600 nm (7000).
General Procedure for the Preparation of Dendritic Manganese Porphyrins 5b-d: A mixture of 5,10,15,20-tetrakis(3,5-dihydroxyphenyl)porphinatomanganese(III) chloride 2 (1 equiv., 2.5 mM, the appropriate poly(benzyl ether) type dendritic bromide (9.6 equiv.), K2CO3 (16 equiv.), and 18-crown-6 (1.6 equiv.) in dry acetone was refluxed for 4-8 d. (To drive the reaction to completion the addition of more dendritic bromide was sometimes necessary.) The solvent was evaporated and the residue taken up in CH2Cl2. The organic phase was washed with water and brine, dried over MgSO4, and the solvent removed in vacuo. Chromatography (silica gel, linear gradient from CH2Cl2 / hexanes to CH2Cl2) afforded the desired products as dark green glasses.
5b: This was prepared as above from 2 and first generation dendritic bromide (72 %). FTIR (KBr) 3031, 2870, 1596, 1452, 1346, 1157, 1055 cm-1; UV/vis (CH2Cl2) λmax (ε) 379 nm (111000), 403 nm (90000), 481 nm (230000), 583 nm (18000), 617 nm (16000); 87
MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 3215.7 (calcd for C212H172N4O24Mn+ 3214.6).
5c: This was prepared as above from 2 and second generation dendritic bromide (72 %). FTIR (KBr) 3031, 2874, 1595, 1449, 1371, 1155, 1053 cm-1; UV/vis (CH2Cl2) λmax (ε) 378 nm (104000), 404 nm (88000), 481 nm (257000), 583 nm (18000), 618 nm (16000); MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 6609.8 (calcd for C436H364N4O56Mn+ 6610.6); Anal. C: 79.03, H: 5.73, N: 0.71 (calcd C: 78.80, H: 5.52, N: 0.84).
5d: This was prepared as above from 2 and third generation dendritic bromide (10 %). FTIR (KBr) 3034, 2869, 1595, 1449, 1375, 1156, 1050 cm-1; UV/vis (CH2Cl2) λmax (ε) 378 nm (98000), 404 nm (84000), 482 nm (209000), 579 nm (15000), 617 nm (14000); MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 13408.3 (calcd for C884H748N4O120Mn+ 13402.5).
General Procedure for the Preparation of Dendritic Free Base Porphyrins 6b-d: A mixture of 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin 3 (70 mg, 0.1 mmol), the appropriate poly(benzyl ether) type dendritic bromide (0.5 mmol), K2CO3 (69 mg, 0.5 mmol) and 18-crown-6 (50 mg, 0.2 mmol) in 20 mL of dry acetone was refluxed for 48 h. After addition of water (100 mL), the aqueous layer was extracted with CH2Cl2 (3 x 50 mL), the combined organic phases washed with brine, dried over MgSO4, and the solvent
88
evaporated. The residue was chromatographed (silica gel, CH2Cl2) to afford the desired porphyrin dendrimers as purple glasses.
6b: This was prepared as above from 3 and first generation dendritic bromide (71 %).
1
H
NMR (400 MHz, CDCl3, 25 oC, TMS): δ 8.85 (broad s, 8 H, β-H), 8.08 (d, 3J (H,H) = 8 Hz, 8 H, Ar-H), 7.46-7.30 (m, 48 H, Ar-H+Ph), 6.87 (d, 4J (H,H) = 2 Hz, 8 H, Ar-o,o’H), 6.68 (t, 4J (H,H) = 2 Hz, 4 H, Ar-p-H), 5.23 (s, 8 H, CH2O), 5.11 (s, 16 H, CH2O), -2.74 (broad s, 2 H, NH);
13
C NMR (100 MHz, CDCl3) δ 160.3, 158.5, 139.5, 136.8,
135.6, 134.9, 131.0, 128.6, 128.1, 127.6, 119.7, 113.1, 106.6, 101.7, 70.2; MS (ES+): m/z = 1888.
6c This was prepared as above from 3 and second generation dendritic bromide (71 %). 1
H NMR (400 MHz, CDCl3, 25 oC, TMS): δ 8.86 (broad s, 8 H, β-H), 8.10 (d, 3J (H,H) =
8 Hz, 8 H, Ar-H), 7.40-7.23 (m, 88 H, Ar-H+Ph), 6.86 (d, 4J (H,H) = 2 Hz, 8 H, Ar-o,o’H), 6.73 (d, 4J (H,H) = 2 Hz, 16 H, Ar-o,o’-H), 6.63 (t, 4J (H,H) = 2 Hz, 4 H, Ar-p-H), 6.58 (t, 4J (H,H) = 2 Hz, 8 H, Ar-p-H), 5.25 (s, 8 H, CH2O), 5.05 (s, 16 H, CH2O), 5.03 (s, 32 H, CH2O), -2.75 (broad s, 2 H, NH); 13C NMR (100 MHz, CDCl3) δ 160.3, 160.2, 158.6, 139.5, 139.3, 136.7, 135.6, 135.0, 128.6, 128.0, 127.5, 119.7, 113.1, 106.6, 106.4, 101.7, 101.6, 70.3, 70.2, 70.1; MS (ES+, NH4OAc): m/z = 3586.
6d: This was prepared as above from 3 and third generation dendritic bromide (77 %). 1
H NMR (400 MHz, CDCl3, 25 oC, TMS): δ 8.84 (broad s, 8 H, β-H), 8.08 (d, 3J (H,H) =
8 Hz, 8 H, Ar-H), 7.38-7.21 (m, 168 H, Ar-H+Ph), 6.87 (d, 4J (H,H) = 2 Hz, 8 H, Ar-o,o’89
H), 6.71 (d, 4J (H,H) = 2 Hz, 16 H, Ar-o,o’-H), 6.65 (d, 4J (H,H) = 2 Hz, 32 H, Ar-o,o’H), 6.62 (t, 4J (H,H) = 2 Hz, 4 H, Ar-p-H), 6.55 (t, 4J (H,H) = 2 Hz, 8 H, Ar-p-H), 6.52 (t, 4
J (H,H) = 2 Hz, 16 H, Ar-p-H), 5.22 (s, 8 H, CH2O), 5.02 (s, 16 H, CH2O), 4.95 (broad
s, 32+64 H, CH2O), -2.75 (broad s, 2 H, NH);
13
C NMR (100 MHz, CDCl3) δ 160.2,
160.1, 160.0, 139.5, 139.2, 136.7, 135.6, 134.9, 128.5, 127.9, 127.5, 119.7, 113.1, 106.5, 106.3, 101.6, 70.0.
References 1. (a) Newkome, G. R.; Moorefield, C. N.; Vögtle, F. Dendritic Molecules: Concepts, Synthesis, Perspectives; VCH: Weinheim, 1996. (b) Top. Curr. Chem. 1998, 197; 2000, 210; 2001, 212. (c) Bosman, A. W.; Jansen, H. M.; Meijer, E. W. Chem. Rev. 1999, 99, 1665. (d) Chow, H.-F.; Mong, T. K.-K.; Nongrum, M. F.; Wan, C.-W. Tetrahedron 1998, 54, 8543. (e) Fréchet, J. M. J.; Hawker, C. J. In Comprehensive Polymer Science, 2nd Suppl.; Aggarwal, S. L.; Russo, S., Eds.; Pergamon Press: Oxford, 1996, p 140. (f) Fréchet, J. M. J. Science, 1994, 263, 1710. (g) Tomalia, D. A.; Naylor, A. M.; Goddard, W. A., III Angew. Chem. Int. Ed. 1990, 29, 138. 2. Hecht, S.; Fréchet, J. M. J. Angew. Chem. Int. Ed. 2001, 40, 74. 3. (a) Chow, H.-F.; Mong, T. K.-K.; Nongrum, M. F.; Wan, C.-W. Tetrahedron 1998, 54, 8543. (b) Smith, D. K.; Diederich, F. Chem. Eur. J. 1998, 4, 1353; (c) Archut, A.; Vögtle, F. Chem. Soc. Rev. 1999, 27, 233. 4. (a) Jin, R.-H.; Aida, T.; Inoue S. J. Chem. Soc., Chem. Commun. 1993, 1260. (b) Jiang, D.-L.; Aida, T. Chem. Commun. 1996, 1523. (c) Sadamoto, R.; Tomioka, N.; Aida, T. J. Am. Chem. Soc. 1996, 118, 3978. (d) Tomoyose, Y.; Jiang, D.-L.; Jin, R.90
H.; Aida, T.; Yamashita, T.; Horie, K.; Yashima, E.; Okamoto, Y. Macromolecules 1996, 29, 5236; (e) Tomioka, N.; Takasu, D.; Takahashi, T.; Aida, T. Angew. Chem. Int. Ed. 1998, 37, 1531. (f) Jiang, D.-L.; Aida, T. J. Am. Chem. Soc. 1998, 120, 10895. (g) Pollak, K. W.; Sanford, E. M.; Fréchet, J. M. J. J. Mater. Chem. 1998, 8, 519. (h) Pollak, K. W.; Leon, J. W.; Fréchet, J. M. J.; Maskus, M.; Abruña, H. D. Chem. Mater. 1998, 10, 30. 5. (a) Dandliker, P. J.; Diederich, F.; Gross, M.; Knobler, C. B.; Louati, A.; Sanford, E. M.
Angew. Chem. Int. Ed. 1994, 33, 1739. (b) Dandliker, P. J.; Diederich, F.;
Gisselbrecht, J.-P.; Louati, A.; Gross, M. Angew. Chem. Int. Ed. 1995, 34, 2725. (c) Dandliker, P. J.; Diederich, F.; Zingg, A.; Gisselbrecht, J.-P.; Gross, M.; Louati, A.; Sanford, E. M. Helv. Chim. Acta 1997, 80, 1773. (d) Collman, J. P.; Fu, L.; Zingg, A.; Diederich, F. Chem. Commun. 1997, 193. (e) Weyermann, P.; Gisselbrecht, J.-P.; Boudon, C.; Diederich, F.; Gross, M. Angew. Chem. Int. Ed. 1999, 38, 3215. (f) Vinogradov, S. A.; Lo, L.-W.; Wilson, D. F. Chem. Eur. J. 1999, 5, 1338. (g) Vinogradov, S. A.; Wilson, D. F. Chem. Eur. J. 2000, 6, 2456. 6. (a) Bhyrappa, P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Am. Chem. Soc. 1996, 118, 5708. (b) Bhyrappa, P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Mol. Catal. A 1996, 113, 109. (c) Bhyrappa, P.; Vaijayanthimala, G.; Suslick, K. S. J. Am. Chem. Soc. 1999, 121, 262. 7. Kimura, M.; Shiba, T.; Muto, T.; Hanabusa, K.; Shirai, H. Macromolecules 1999, 32, 8237. 8. Tomalia, D. A.; Baker, H.; Dewald, J. R.; Hall, M.; Kallos, G.; Marin, S.; Roeck, J.; Ryder, J.; Smith, P. Polym. J. 1985, 17, 117. 91
9. Murat, M.; Grest, G. S. Macromolecules 1996, 29, 1278. 10. Boris, D.; Rubinstein, M. Macromolecules 1996, 29, 7251. 11. Lescanec, R. L.; Muthukumar, M. Macromolecules 1990, 23, 2280. 12. Mourey, T. H.; Turner, S. R.; Rubinstein, M.; Fréchet, J. M. J.; Hawker, C. J.; Wooley, K. L. Macromolecules 1992, 25, 2401. 13. De Backer, S.; Prinzie, Y.; Verheijen, W.; Smet, M.; Desmedt, K.; Dehaen, W.; De Schryver, F. C. J. Phys. Chem. A 1998, 102, 5451. 14. (a) Hawker, C. J.; Fréchet, J. M. J. J. Am. Chem. Soc. 1990, 112, 7638. (b) Hawker, C. J.; Fréchet, J. M. J. J. Chem. Soc., Chem. Commun. 1990, 1010. 15. Rocha Gonsalves, A. M. d’A.; Varejao, J. M. T. B.; Pereira, M. M. J. Heterocyclic Chem. 1991, 28, 635. 16. (a) Cytochrome P-450: Structure, Mechanism and Biochemistry; Ortiz de Montellano, P., Ed.; Plenum Press: New York, 1995. (b) Metalloporhyrins in Catalytic Oxidations; Sheldon, R. A., Ed.; Marcel Dekker: New York, 1994. (c) Metalloporphyrin Catalyzed Oxidations; Montanari, F.; Casella, L., Ed.; Kluwer: London, 1995. (d) Sono, M.; Roach, M. P.; Coulter, E. D.; Dawson, J. Chem. Rev. 1996, 96, 2841. 17. Dolphin, D. The Porphyrins; Academic Press: New York, 1978. 18. (a) Pasternack, R. F.; Bustamante, C.; Collings, P. J.; Gianetto, A.; Gibbs, E. J. J. Am. Chem. Soc. 1993, 115, 5393. (b) Pasternack, R. F.; Schaefer, K. F.; Hambright, P. Inorg. Chem. 1994, 33, 2062. 19. Gorman, C. B.; Parkhust, B. L.; Su, W. L.; Chen, K. Y. J. Am. Chem. Soc. 1997, 119, 1141. 92
20. Strachan, J. P.; Gentemann, J. S.; Kalsbeck, W. A.; Lindsey, J. S.; Holten, D.; Bocian, D. F. J. Am. Chem. Soc. 1997, 119, 11191. 21. Kim, J. B.; Leonard, J. J.; Longo, F. R. J. Am. Chem. Soc. 1972, 94, 3986. 22. Maiti, N. C.; Mazumdar, S.; Periasamy, N. J. Phys. Chem. 1995, 99, 10708. 23. Edward, J. J. Chem. Ed. 1970, 47, 261. 24. James, D. A.; Arnold, D. P.; Parsons, P. G. Photochem. Photobiol. 1994, 59, 441. 25. Bhyrappa, P.; Wilson, S. R.; Suslick, K. S. J. Am. Chem. Soc. 1997, 119, 8492. 26. Lakowiczs, J. R. Topics in Fluorescence Spectroscopy; Vol.1, Plenum Press: New York, 1991. 27. Gradyushko, A. T.; Tsvirko, M. P. J. Am. Chem. Soc. 1970, 92, 535. 28. Crutzen, M.; Ameloot, M.; Boens, N.; Negri, R. M.; De Schryver, F. C. J. Phys. Chem. 1993, 97, 8133.
93
Chapter 4:
Site Isolation in Porphyrin Core Dendrimers and their Isomeric Linear Analogs – The Effect of Polymer Architecture
Abstract A comparative study of core encapsulation in poly(benzyl ether) type dendrimers and their exact linear analogs utilizing energy transduction from the polymer backbone to a porphyrin core is described. Three series of structural isomers differing in the degree of branching were synthesized and showed remarkably different hydrodynamic properties allowing for evaluation of their relative molecular sizes in solution. Fluorescence excitation revealed strongly morphology dependent intramolecular energy transfer in the three investigated porphyrin core isomers series. The energy transduction seems to be governed by the average distance of the internal repeat units that act as localized donor chromophores. Even at high generations, the dendrimers exhibited very efficient energy transfer thereby indicating superior site isolation of the central porphyrin moiety.
94
Introduction The encapsulation of functional cores within dendritic1,2 shells has received considerable interest in recent years.3 This approach allows for tailoring of the overall molecular properties via peripheral modification and in addition enables tuning of the properties of the core itself. In some cases, there have been observations of dramatic influence of morphology4 and focal point geometry5 on the efficiency of energy transduction, i.e. the ‘antenna effect,’ within the dendrimer architecture, in particular of the poly(benzyl ether) type. These stimulating results encourage further detailed investigation of such unique dendritic properties. With regard to site isolation, porphyrins and their metal complexes have been thoroughly investigated as core moieties due to their distinct photophysical, electrochemical, and catalytic characteristics.4b,6 Recently, we have reported on alternative architectures based on star-shaped branched-linear copolymers to achieve efficient site isolation.7 In addition, Hawker and coworkers succeeded in the synthesis of exact linear analogs of poly(benzyl ether) dendrimers.8 By further exploring the utility of such building blocks to prepare and study different structural isomers having a porphyrin probe located at the core, further insight into the role of the polymer backbone in site isolation of core functionality can be gained. Here, we report on the synthesis and characterization of structural isomers of porphyrin core poly(benzyl ethers) ranging from a dendritic over a 8-arm linear to a 4-arm linear star series. Furthermore, an intramolecular energy transfer study involving the polymer backbone itself is presented and the results are related to previously reported morphology and antenna effects in dendrimers of the poly(benzyl ether) type.4,5
95
Results and Discussion Synthesis and Characterization. To obtain the desired isomeric porphyrin core poly(benzyl ether) series, benzylic bromides of the respective different structural isomers have been coupled in a Williamson ether synthesis to polyphenolic porphyrin cores. For comparison, a third generation Fréchet-type dendron, [GD-3]-Br, and its exact structural analog, [GL-3]-Br, are depicted in Scheme 4.1. Both compounds have the same number of internal 3,5-dialkoxybenzyl ether and terminal benzyl ether groups are indeed structural isomers of each other. Scheme 4.1
O
O
O
O
O
O
O
O O
O
O
O
O
O
O
O
O
O
O
O
O
O
O Br
O
O
O
O
O
Br
[GD-3]-Br
[GL-3]-Br
By using combinations of an octavalent porphyrin core with the dendritic as well as linear isomeric bromides of the same generation and a tetravalent core with the linear analogs of the next higher generation, three different porphyrin core poly(benzyl ether) series 1a-d, 2b-d, 3a-d (Scheme 4.2) were designed. To further demonstrate the isomeric relationships, a summary of the chemical composition of all investigated compounds is given in Table 4.1. Please note that since the linear and dendritic poly(benzyl ether) building blocks of the first generation are identical, compound 2a is the same as 1a and will therefore be omitted in the following.
96
Scheme 4.2 L-[G-n] D-[G-n]
D-[G-n]
D-[G-n]
N
L-[G-n]
D-[G-n]
HN
L-[G-n]
L-[G-n]
N
L-[G-n]
HN
N
HN
NH
N
L-[G-n] NH
D-[G-n]
N D-[G-n]
D-[G-n]
NH
L-[G-n]
D-[G-n]
L-[G-n]
N L-[G-n]
L-[G-n]
L-[G-n] L-[G-n]
Dendrimer Series [GD-n]8P
Branched Linear Series [GL-n]8)
Linear Series [GL-n]4P
1a-d
2b-d
3a-d
O
Bn
O
Bn n
O
[GD-n] =
Table 4.1.
Bn
[GL-n] = OBn n
Chemical Composition of Structural Porphyrin Core Poly(benzyl ether) Isomer Series 1a-d, 2b-d, and 3a-d (compound 2a is identical to 1a).
compound
series
generation
formula
internal units
terminal units
1a
[GD-n]8P
n=1
C212H174N4O24
8
16
b
n=2
C436H366N4O56
24
32
c
n=3
C884H750N4O120
56
64
d
n=4
C1780H1518N4O248
120
128
n=2
C436H366N4O56
24
32
c
n=3
C884H750N4O120
56
64
d
n=4
C1780H1518N4O248
120
128
n=2
C240H198N4O28
12
16
b
n=3
C464H390N4O60
28
32
c
n=4
C912H774N4O124
60
64
d
n=5
C1808H1542N4O252
124
128
2b
3a
[GL-n]8-P
[GL-n]4P
For illustration purposes, the actual chemical structures of the three third generation isomers 1c, 2c, 3c are shown in Scheme 4.3 (structures drawn to scale in their extended conformations).
97
Scheme 4.3 O
O
OO
O
OO O
OO O O
O
O O
O
O
O
O
O
O
O
O O
O
O
O
O O
O
O
O
O
O
OO
O
O
O
O
O
O
O
OO
O O
O
O
O
O O
O
O
O O O O O
O O
O
O
O
O
O
O
O
N
O
O
O O
O
O
HN
O
O
NH
O
O
O
O
O
N
O
O
O
O
O
O
O
O O
O O
O
O
O
O
O
O
O
O
O O O
O
O
O O
O O
O
O
O
O
O
O
O
O
O
O
O
O
O
O O
O O
O
O
O
OO
O O
O
O
O
O
O
O
O O O
O O
O
OO
O
O
O
OO OO
1c
O
N
HN
NH
N
O
O
O
O
O
O
OO
O
O
O
O
O
O
O
O
O
O
O O
O O
O
O
O
O
O
O
O
OO
O O
O
O
O
O
O
O
O
O
O
O O
O
O
O
O
O
O
O O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O O
O
O
O
O
O
O
O
O
O
O
O
O
2c
O
O O
O
O O
O O
O
O
O
O
O
O O
O
O O
O
O
O O
O O O O
O O O
O
O O
O O O O O
O
O O
O O
O
O
O O O
O
O O O
O O
O
O
O O O
O
O O O
O
O N
HN
NH
N
O O
O
O
O O O
O O
O O
O
O O O O
O
O O
O O O
O
O O O O
O
O O
O O O
O O O O O
O
O
O
O O O
O O
O O
O O
O
O
O O
O
O
O O
O
3c
O
O O
O
O
98
O
Characterization
of
the
individual
isomer
series
by
gel
permeation
chromatography (GPC) gave first insight into their size in solution since the elution time (or volume) is directly correlated to the hydrodynamic radius of the analyzed species. The GPC traces comparing 1c, 2c, and 3c impressively demonstrate very different solution behavior of these three isomers (Figure 4.1).
signal intensity / a.u.
3c 2c 1c
30
elution time / min
40
Figure 4.1. Representative GPC traces of three isomers 1c, 2c, and 3c.
The calibration of the GPC using linear polystyrene standards, led to surprisingly accurate molecular weights determination in the case of the linear 4-arm series 3a-d. Hence, the linear portion of macromolecules seem dominate the hydrodynamic properties leading to mostly random coil conformations in solution. The increased branching in the case of the 8-arm series 2b-d and the true dendrimers 1a-d caused negative deviations due to the smaller hydrodynamic radii as compared to the linear polystyrene standards, consistent with their more compact shape in solution.1c,d Clearly, the connectivity gives rise to a better shielding of the core functionality. The GPC data are summarized in Table 4.2 and the correlation of the molecular weights, as determined by GPC, with the actual molecular weights is shown in Figure 4.2. 99
Table 4.2.
GPC Characterization of Structural Porphyrin Core Poly(benzyl ether) Isomer Series 1a-d, 2b-d, and 3a-d (compound 2a is identical to 1a). compound
tR / min
Mn / D
MWtheory / D
PD
1a b c d
40.4
3261
3162
1.005
38.8
5496
6558
1.009
37.3
8857
13350
1.026
36.4
13347
26933
1.050
2b c d
38.6
5828
6558
1.008
36.6
12030
13350
1.024
33.4
22500
26933
1.020
3a b c d
39.4
4515
3586
1.007
37.6
8183
6982
1.014
34.3
15000
13774
1.010
29.0
28000
27358
1.010
35000
P eak M olecular W eight
30000 25000 20000 15000 10000 5000 0 0
5000
10000
15000
20000
25000
30000
35000
E x act M olec ular W eight Figure 4.2. Correlation of molecular weight by GPC and actual molecular weight for the dendritic series 1a-d (#), the 8-arm linear series 2b-d (%), and the 4-arm linear series 3a-d (!). Linear polystyrene standard calibration (........) is shown.
100
In order to study the electronic properties of the materials, compounds modeling the individual chromophore subunits were synthesized. 3,5-Dimethoxybenzyl methyl ether 4 and benzyl methyl ether 5 were chosen as model compounds for the internal and terminal units, respectively, while tetrakis(3,5-dimethoxyphenyl)porphyrin 6 and tetrakis(4-methoxyphenyl)porphyrin 7 served as models for the core (Scheme 4.4). Scheme 4.4 OMe MeO
MeO
OMe
OMe
MeO
OMe
N
4
HN
OMe
N
HN
NH
N
MeO MeO
OMe
N
NH
OMe
MeO
OMe
OMe OMe
5
6
7
Absorption/Emission Properties and Energy Transfer Studies. Energy transfer within dendritic architectures9 is particularly attractive since the high ratio of terminal donor to core acceptor chromophores allows for excitation energy funneling to the core. Among the systems involving the dendrimer backbone in the energy transduction are, rather surprisingly, also non-conjugated poly(benzyl ether) dendrimers. The ‘antenna effect’ arising from indirect excitation of a dendritic core moiety via efficient light-harvesting of the poly(benzyl ether) dendrimer backbone and subsequent energy transfer to the core was found to lead to considerably enhanced emission from the core4b,c,5 and even multiphoton processes4a in case of sufficient site isolation. Furthermore, the focal point
101
geometry seemed to play an important role in energy funneling.5 While Jiang and Aida have varied the number of dendron subunit around a free base porphyrin core,4b a different approach was taken to investigate morphology effects on the energy transfer process by comparing the structural isomer series 1b-d, 2b-d, and 3b-d. Due to the negligible absorption of the dendritic backbone in low generations, compounds 1a and 3a could not be investigated. The absorption spectra of the three different isomer series clearly show a comparable absorbance of the poly(benzyl ether) backbone within each generation as well as the expected doubling in absorbance with increasing generation (Figure 4.3). Compounds 3b-d show slightly higher absorbances due to the incorporation of four more branched units (Table 4.1). The Soret bands of the porphyrin core exhibit minor bathochromic shifts in the order of 3-4 nm that are mostly pronounced in the dendrimer series 1b-d and are attributed to increasing core encapsulation.4b,6r
absorbance
d
c
b
300
400
500
wavelength / nm
600
700
Figure 4.3. Absorption spectra of isomer series 1b-d (____), 2b-d (........), and 3b-d (----) in THF (25 oC).
102
Emission from the porphyrin core was observed by either direct excitation (Soret or Q-bands) or by indirect excitation (dendrimer backbone). This can be demonstrated by obtaining the corresponding excitation spectra showing all chromophore subunits that are responsible for population of the emitting excited state of the porphyrin core. For example, one set of isomers (1d, 2d, 3d) depicted in Figure 4.4 clearly shows different
intensity
contributions of the poly(benzyl ether) backbone in the energy transfer.
250
300 350
400
450
wavelength / nm
500
550
600
Figure 4.4. Excitation spectra (λem=653nm) for isomers 1d (____), 2d (........), and 3d (----) in THF (25 oC).
Comparison of the excitation and the absorption spectra enables one to quantify the energy transfer efficiency (ΦET).10 With increasing generation, the dendrimer series 1b-d exhibits only a slight decline in ΦET, while the branched linear series 2b-d shows a significant and the linear series 3b-d the steepest decrease in ΦET (Figure 4.5). Clearly, there is a pronounced morphology dependence on the energy transfer event in the investigated molecules.
103
100
89.7 88.4
energy transfer efficiency / %
87.8 80
83.9
84.8 74.1
60
57.0 54.5
40 34.2 20
1 2 0
b
c
3 d
Figure 4.5. Energy transfer efficiencies of isomer series 1b-d, 2b-d, and 3b-d in THF (25 oC).
In order to explain these results, the individual chromophore subunits were studied (Scheme 4.4). UV/vis spectroscopy revealed a much stronger absorbance of 4 compared to 5 indicating that the photophysical properties of the dendrimer backbone are dominated by the interior branching units. This is further supported by the observed absorption maximum and the vibrational fine structure (Figure 4.6, inset). By adding the absorbances of all individual components to construct ‘ensemble’ spectra, a good correlation with the absorption spectra of the actual macromolecule was found (Figure 4.6). This spectral comparison furthermore demonstrates the apparent core isolation in the dendrimers as indicated by the relatively large shift of the Soret band.
104
500000
3000
2000
-1
400000
1000
300000
5
-1
ε / l*mol *cm
4
0 250
275
200000
l
300
th /
325
350
100000
0 300
400
500
wavelength / nm
600
700
Figure 4.6. Comparison of an ‘ensemble’ spectrum consisting of the combined absorption spectra of all individual chromophore subunits (120 x 4 + 128 x 5 + 6, ) with compound 1d (………). The inset shows the absorption spectra of the branched (4) and terminal units (5).
This finding suggests no significant electronic cooperativity of the dendron fragments. Hence in a first approximation, we can assume that the observed macroscopic energy transfer arises from a combination of individual events involving single chromophore subunits. Therefore, the overall average distance of the 3,5-dialkoxybenzyl donor chromophores to the acceptor will determine ΦET in the system as illustrated in Figure 4.7 (see also Scheme 4.3). Obviously, this average distance will largely depend on the molecular architecture, i.e. connectivity, and should therefore differ significantly by comparing the isomer series as found in the energy transfer experiments.
105
Figure 4.7. Illustration of morphology dependent energy transfer arising from a collective interaction of individual donor chromophores with an acceptor core. The average donor acceptor separation increases with the linearity of the system from a) dendritic (1c) over b) branched linear (2c) to c) linear (3c) leading to a reduced energy transfer efficiency.
To further validate this assumption, a more detailed analysis of the resonance energy transfer11 in the model systems was carried out by calculating the Förster radius R0,12 i.e. the distance at which ΦET = 0.5, using:
106
R0 = 6
0.5291κ 2 J n 4NA
(1)
where κ2 is the orientation factor, J is the overlap integral of the fluorescence intensity of the donor and the molar extinction coefficient of the acceptor normalized by the frequency expressed in wavenumbers, n is the index of refraction of the solvent, and NA is Avogadro’s constant. The overlap integrals were calculated to be J(4→6) = 1.788⋅10-14 mol-1cm6 and J(4→7) = 1.697⋅10-14 mol-1cm6 giving rise to Förster radii of R0(4→6) = 3.73 nm (series 1b-d and 2b-d) and R0(4→7) = 3.70 nm (series 3b-d). Although the R0 values for energy transfer from 5→6 and 5→7 were calculated to be 3.50 nm in both cases, the contribution of the terminal groups to the overall energy transfer process is almost negligible due to their very low absorbance. This is supported by the few available experimental size data, since compound 1c has a hydrodynamic radius of approximately 1.7 nm in THF,6r which is much smaller than the Förster radius (3.73 nm) allowing efficient energy transfer to take place (ΦET = 88.4%). For the linear poly(benzyl ether) chains on the other hand, we have to rely on molecular modeling that predicts a 0.6 nm separation of adjacent 3,5-dialkoxybenzyl chromophores. Therefore in a good solvent for the polymer such as THF,13 compound 3c in its fully extended conformation would have a radius of approximately 9.0 nm (15x0.6nm) giving rise to an average distance of donor acceptor distance of 4.5 nm, which is in good agreement with the observed value of 3.7 nm (ΦET = 0.55, which corresponds approximately to the Förster radius).
107
Conclusion For the first time, a comparative study of site isolation as a function of the architecture of the shielding polymer backbone has been carried out. The design of exact linear analogs of dendritic poly(benzyl ether) wedges allowed for the synthesis of three structural isomer series having a porphyrin probe at the core. The isomers displayed dramatically different hydrodynamic properties as evidenced by their elution behavior in GPC analysis. First static absorption and emission experiments led to the observation of strongly morphology dependent intramolecular energy transfer in the different porphyrin core isomers series. The energy transduction from the poly(benzyl ether) backbone to the core was found to be facilitated in the dendritic case, whereas in the linear cases significant decreases in the energy transfer efficiencies were observed at higher molecular weights. Initial spectral analysis revealed the 3,5-dialkoxybenzyl ether internal units as responsible donor chromophores, whose average distance to the porphyrin core dictates the energy transfer efficiency. The extremely efficient energy transfer of the dendrimers even in higher generations results from relatively short distances of the internal donor units to the acceptor core, clearly suggesting superior encapsulation in the dendritic case.
Experimental General Methods: Dendritic substituents are denoted [GD-n] and their structural linear isomers [GL-n], where in both cases n refers to the generation number. Consequently, porphyrin core dendrimers and their structural linear isomers are referred to as [GD-n]8P, [GL-n]8P, and [GD-(n+1)]4P. Note that the first generation linear and dendritic substituents are identical. For this reason, no linear analog corresponding to [GD-1]8P is shown. All 108
reagents were used as received and without further purification, unless otherwise noted. Dendritic poly(benzyl ether) type bromides14 ([GD-n]-Br) were synthesized as described in detail in Chapter 2, where as the linear poly(benzyl ether) type bromides ([GL-n]-Br) were prepared according to the literature.5 The porphyrin core dendrimers [GD-n]8P were synthesized as described in Chapter 3. Tetrakis(3,5-dimethoxyphenyl)porphyrin 615 and tetrakis(4-methoxyphenyl)porphyrin 716 were prepared from pyrrole and the respective aromatic aldehydes using Adler-Longo condensation conditions.17 Tetrakis(4-hydroxyphenyl)porphyrin (THPP) and tetrakis(3,5-dihydroxyphenyl)porphyrin18 (TDHPP) were prepared by boron tribromide deprotection19 of 7 and 6, respectively. 3,5Dimethoxybenzyl methyl ether 4 was prepared as described in the literature.20 Column chromatography was carried out with Merck silica gel for flash columns, 230-400 mesh. NMR spectra were recorded on a Bruker AM 200 (200 MHz) spectrometer with the residual protonated solvent peak as internal standard. GPC was carried out on a Waters chromatograph connected to a Waters 410 differential refractometer with THF as the carrier solvent. Absorption spectra were recorded in degassed THF solution (containing no stabilizers) on a Cary 50 UV-Visible Spectrophotometer. Fluorescence spectra were measured of degassed solutions (1cm cells, ODmax < 0.2) using an ISA/SPEX Fluorolog 3.22 equipped with a 450 W Xe lamp, double excitation and double emission monochromators, and a digital photon-counting photomultiplier. Excitation spectra of compounds 1b-d, 2b-d, and 3b-d were acquired at λem = 653 nm with slit widths set to 2 nm bandpass for both excitation and emission. Emission spectra of model compounds 4 and 5 were measured at λexc = 280 nm and λexc = 258 nm, respectively, and slit widths were set to 2 nm bandpass for excitation as well as 4 nm bandpass for emission. 109
Correction for variations in lamp intensity over time and wavelength was achieved with a solid-state silicon photodiode as the reference. The spectra were further corrected for variations in photomultiplier response over wavelength and for the path difference between the sample and the reference by multiplication with emission correction curves generated on the instrument. The energy transfer efficiencies for compounds 1b-d, 2b-d, and 3b-d were calculated from the ratio of the integrated donor excitation and absorption spectra normalized at the acceptor Soret band.
General Procedure for Preparation of Porphyrin Cored Linear Poly(benzyl ethers): The linear poly(benzyl ether) dendritic bromides were coupled to THPP and TDHPP, respectively, under standard Williamson ether conditions employing K2CO3 as the base and 18-crown as phase transfer catalyst in refluxing acetone. To drive the reactions to completion, excess of the benzylic bromides (1.5-2.0 equiv. per phenolic group) was used. After initial failure in preparing materials beyond the second generation, it was found that replacing acetone with a THF/DMF (4:1) mixture enabled the successful synthesis of higher generation porphyrin core dendritic analogs. Purification was carried out as follows: filtered product mixtures were dissolved in a minimal amount of CH2Cl2 in a large beaker equipped with a magnetic stir bar. Diethyl ether was gradually added until the substituted porphyrin precipitated from this mixture leaving excess benzylic bromides suspended in the ether layer. This process was repeated several times to afford the product in satisfactory analytical purity. The supernatants were collected and later combined for further precipitation using flash chromatography to recover unreacted starting material in form of the poly(benzyl ether) type bromides and alcohols. 110
[GL-2]4P: This was prepared as above from THPP and [GL-2]-Br (41 % yield). 1H-NMR (200 MHz, CDCl3, 25 °C): δ 8.83 (s, 8 H, β-H), 8.07 (d, 3J (H,H) = 8 Hz, 8 H, Ar-H), 7.24-7.47 (m, 80 H, Ar-H), 6.52-6.84 (m, 36 H, Ar-H), 5.25-5.28 (m, 32 H, CH2O), 4.96 (s, 16 H, CH2O).
[GL-3]4P: This was prepared as above from THPP and [GL-3]-Br (61 % yield). 1H-NMR (200 MHz, CDCl3, 25 °C): δ 8.82 (s, 8 H, β-H), 8.05 (d, 3J (H,H) = 8 Hz, 8 H, Ar-H), 7.24-7.42 (m, 160 H, Ar-H), 6.85 (d, 3J (H,H) = 8 Hz, 8 H, Ar-H), 6.49-6.85 (m, 76 H, Ar-H), 5.21 (s, 8 H, CH2O), 5.06 (s, 8 H, CH2O), 4.88 (m, 96 H, CH2O).
[GL-4]4P: This was prepared as above from THPP and [GL-4]-Br (37 % yield). 1H-NMR (200 MHz, CDCl3, 25 °C): δ 8.85 (s, 8 H, β-H), 8.01(d, 3J (H,H) = 8 Hz, 8 H, Ar-H), 7.18-7.25 (m, 328 H, Ar-H), 6.54 (m, 180 H, Ar-H), 4.89 (s, 8 H, CH2O), 4.81 (m, 216 H, CH2O).
[GL-5]4P: This was prepared as above from THPP and [GL-5]-Br (42 % yield). 1H-NMR (200 MHz, CDCl3, 25 °C): δ 8.85 (s, 8 H, β-H), 7.12-7.27 (m, 640 H, Ar-H), 6.56 (m, 372 H, Ar-H), 4.90 (m, 256 H, CH2O), 4.82-4.88 (m, 240 H, CH2O).
[GL-2]8P: This was prepared as above from TDHPP and [GL-2]-Br (51 % yield). 1HNMR (200 MHz, CDCl3, 25 °C): δ 8.84 (s, 8 H, β-H), 7.41 (d, 4J (H,H) = 4 Hz, 8 H, Ar-
111
H), 7.17-7.41 (m, 160 H, Ar-H), 6.98 (s, 4 H, Ar-H), 6.44-6.66 (complex m, 72 H, Ar-H), 5.02 (s, 16 H, CH2O), 4.86 (s, 32 H, CH2O), 4.79 (m, 32 H, CH2O).
[GL-3]8P: This was prepared as above from TDHPP and [GL-3]-Br (67 % yield). 1HNMR (200 MHz, CDCl3, 25 °C): δ 8.85 (s, 8 H, β-H), 7.12-7.25 (m, 320 H, Ar-H), 6.426.53 (complex m, 168 H, Ar-H), 4.76-4.92(m, 224 H, CH2O).
[GL-4]8P: This was prepared as above from TDHPP and [GL-4]-Br (12 % yield). 1HNMR (200 MHz, CDCl3, 25 °C): δ 8.86 (s, 8 H, β-H), 7.19-7.25 (m, 640 H, Ar-H), 6.436.54 (m, 360 H, Ar-H), 4.82-4.89 (m, 494 H, CH2O).
Preparation of Porphyrin Core Dendrimer [GD-4]8P. [GD-4]-Br (2.0 g, 0.597 mol) was dissolved in 50 mL of acetone, followed by the addition of TDHPP (445 mg, 59.7 mmol), K2CO3 (2.0 g, 14 mmol), and 18-crown-6 (50 mg). The mixture was heated at reflux under N2 for 21 days in the dark and purified by fractional precipitation from ether. When conducted in a THF/DMF (4:1) solution, the same reaction was complete in 6 hours with higher yields. The latter afforded dark purple-brown crystals in 37 % yield. 1H-NMR (200 MHz, CDCl3, 25 °C): δ 8.87 (s, 8 H, β-H), 7.11-7.33 (m, 640 H, Ar-H), 6.42 (m, 32 H, Ar-H), 6.32 (m, 96H, Ar-H), 4.94 (m, 192 H, CH2O), 4.67 (s, 16 H, CH2O),4.58 (s, 480 H, CH2O).
112
References 1. (a) Newkome, G. R.; Moorefield, C. N.; Vögtle, F. Dendritic Molecules: Concepts, Synthesis, Perspectives; VCH: Weinheim, 1996. (b) Top. Curr. Chem. 1998, 197; 2000, 210; 2001, 212. (c) Bosman, A. W.; Jansen, H. M.; Meijer, E. W. Chem. Rev. 1999, 99, 1665. (d) Fréchet, J. M. J.; Hawker, C. J. In Comprehensive Polymer Science, 2nd Suppl.; Aggarwal, S. L.; Russo, S., Eds.; Pergamon Press: Oxford, 1996, p 140. (e) Fréchet, J. M. J. Science, 1994, 263, 1710. (f) Tomalia, D. A.; Naylor, A. M.; Goddard, W. A., III Angew. Chem. Int. Ed. 1990, 29, 138. 2. For reviews on functional dendrimers cosult: (a) Chow, H.-F.; Mong, T. K.-K.; Nongrum, M. F.; Wan, C.-W.
Tetrahedron 1998, 54, 8543. (b) Smith, D. K.;
Diederich, F. Chem. Eur. J. 1998, 4, 1353. (c) Archut, A.; Vögtle, F. Chem. Soc. Rev. 1999, 27, 233. 3. Hecht, S.; Fréchet, J. M. J. Angew. Chem. Int. Ed. 2001, 40, 74. 4. (a) Jiang, D.-L.; Aida, T. Nature 1997, 388, 454. (b) Jiang, D.-L.; Aida, T. J. Am. Chem. Soc. 1998, 120, 10895. (c) Sato, T.; Jiang, D.-L.; Aida, T. J. Am. Chem. Soc. 1999, 121, 10658. 5. Kawa, M.; Fréchet, J. M. J. Chem. Mater. 1998, 10, 286. 6. (a) Jin, R.-H.; Aida, T.; Inoue S. J. Chem. Soc., Chem. Commun. 1993, 1260. (b) Dandliker, P. J.; Diederich, F.; Gross, M.; Knobler, C. B.; Louati, A.; Sanford, E. M. Angew. Chem. Int. Ed. 1994, 33, 1739. (c) Dandliker, P. J.; Diederich, F.; Gisselbrecht, J.-P.; Louati, A.; Gross, M. Angew. Chem. Int. Ed. 1995, 34, 2725. (d) Tomoyose, Y.; Jiang, D.-L.; Jin, R.-H.; Aida, T.; Yamashita, T.; Horie, K.; Yashima, E.; Okamoto, Y. Macromolecules 1996, 29, 5236. (e) Jiang, D.-L.; Aida, T. Chem. 113
Commun. 1996, 1523; (f) Sadamoto, R.; Tomioka, N.; Aida, T. J. Am. Chem. Soc. 1996, 118, 3978. (g) Bhyrappa, P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Am. Chem. Soc. 1996, 118, 5708; (h) Bhyrappa, P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Mol. Catal. A 1996, 113, 109. (i) Dandliker, P. J.; Diederich, F.; Zingg, A.; Gisselbrecht, J.-P.; Gross, M.; Louati, A.; Sanford, E. M. Helv. Chim. Acta 1997, 80, 1773. (j) Collman, J. P.; Fu, L.; Zingg, A.; Diederich, F. Chem. Commun. 1997, 193. (k) Pollak, K. W.; Sanford, E. M.; Fréchet, J. M. J. J. Mater. Chem. 1998, 8, 519. (l) Pollak, K. W.; Leon, J. W.; Fréchet, J. M. J.; Maskus, M.; Abruña, H. D. Chem. Mater. 1998, 10, 30. (m) Bhyrappa, P.; Vaijayanthimala, G.; Suslick, K. S. J. Am. Chem. Soc. 1999, 121, 262. (n) Kimura, M.; Shiba, T.; Muto, T.; Hanabusa, K.; Shirai, H. Macromolecules 1999, 32, 8237. (o) Weyermann, P.; Gisselbrecht, J.-P.; Boudon, C.; Diederich, F.; Gross, M. Angew. Chem. Int. Ed. 1999, 38, 3215. (p) Vinogradov, S. A.; Lo, L.-W.; Wilson, D. F. Chem. Eur. J. 1999, 5, 1338. (q) Vinogradov, S. A.; Wilson, D. F. Chem. Eur. J. 2000, 6, 2456. (r) Matos, M. S.; Hofkens, J.; Verheijen, W.; De Schryver, F. C.; Hecht, S.; Pollak, K. W.; Fréchet, J. M. J.; Forier, B.; Dehaen, W. Macromolecules 2000, 33, 2967. 7. (a) Hecht, S.; Ihre, H.; Fréchet, J. M. J. J. Am. Chem. Soc. 1999, 121, 9239. (b) Hecht, S.; Vladimirov, N.; Fréchet, J. M. J. J. Am. Chem. Soc. 2001, 123, 18. 8. Hawker, C. J.; Malmström, E. E.; Frank, C. W.; Kampf, J. P. J. Am. Chem. Soc. 1997, 119, 9903. 9. Adronov, A.; Fréchet, J. M. J. Chem Commun. 2000, 1701.
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10. (a) Weber, G.; Teale, F. W. J. Trans. Faraday. Soc. 1958, 54, 640. (b) Stryer, L.; Haugland, R. P. Proc. Natl. Acad. Sci. U.S.A. 1967, 58, 719. (c) Mugnier, J.; Pouget, J.; Bourson, J.; Valeur, B. J. Lumin. 1985, 33, 273. 11. Consult standard photochemistry textbooks: (a) Turro, N. J. Modern Molecular Photochemistry; University Science Books: Sausalito, 1991. (b) Gilbert, A.; Baggott, J.
Essentials of Molecular Photochemistry; CRC Press: Boca Raton, 1991. (c)
Klessinger, M.; Michl, J. Excited States and Photochemistry of Organic Molecules; VCH: Weinheim, 1995. 12. (a) Förster, T. Fluoreszenz Organischer Verbindungen; Vandenhoech and Ruprech: Göttingen, 1951. (b) Van der Meer, W. B.; Coker, G., III; Chen, S.-Y. Resonance Energy Tranfer, Theory and Data; VCH: Weinheim, 1994. 13. Jeong, M.; Mackay, M. E.; Vestberg, R.; Hawker, C. J. in press. 14. (a) Hawker, C. J.; Fréchet, J. M. J. J. Am. Chem. Soc. 1990, 112, 7638. (b) Hawker, C. J.; Fréchet, J. M. J. J. Chem. Soc., Chem. Commun. 1990, 1010. 15. Tsuchida, E.; Komatsu, T.; Hasegawa, E.; Nishide, H. J. Chem. Soc., Dalton Trans. 1990, 2713. 16. Gonsalves, A. M. d'A.; Varejao, Jorge M. T. B.; Pereira, Mariette M. J. Heterocycl. Chem. 1991, 28, 635. 17. (a) Kim, J. B.; Adler, A. D.; Longo, F. R. In The Porphyrins; Dolphin, D., Ed.; Academic Press: New York, 1978; Vol. I, Part A, p 85. (b) Rocha Gonsalves, A. M. d’A.; Varejao, J. M. T. B.; Pereira, M. M. J. Heterocyclic Chem. 1991, 28, 635. 18. James, D. A.; Arnold, D. P.; Parsons, P. G. Photochem. Photobiol. 1994, 59, 441. 19. McOmie, J. F.; Watts, M. W. Tetrahedron 1968, 24, 2289. 115
20. Elix, J. A.; Jayanthi, V. K. Aust. J. Chem. 1987, 40, 1841.
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Chapter 5:
Encapsulation of Functional Moieties within Branched Star Polymers
Abstract Porphyrin and pyrene photoactive cores, have been encapsulated within an isolating polymeric shell using an efficient and general strategy based on the use of dendritic initiators for the ring opening polymerization of ε-caprolactone to yield star polymers having a functional core. Convenient modification of the core as well as the end-group functionalities further increases the synthetic utility of the described approach. The isolation of the core functionalities has been studied using fluorescence quenching and fluorescence resonance energy transfer (FRET) techniques as well as solvatochromic probes. With increasing chain length as well as solvent polarity, enhanced site isolation of the core has been observed. These findings have been correlated to actual molecular dimensions independently measured by pulsed field gradient spin echo (PGSE) NMR. The developed synthetic methodology offers a rapid route to efficient encapsulation of functional moieties and therefore has potential for the design of novel materials. This chapter has been reproduced in part with permission from J. Am. Chem. Soc. 1999, 121, 9239-9240 and J. Am. Chem. Soc. 2001, 123, 18-25. Copyright 1999 and 2001 American Chemical Society.
117
Introduction In recent years, one of the major objectives in dendrimer chemistry1 has been the encapsulation of active core functionalities within dendritic backbones.2 Numerous examples of such structures have shown profound effects of the dendrimer shell on the core properties, and impressively demonstrated the importance of this site isolation concept.3 The use of dendritic non-natural building blocks to mimic enzyme functions4 will ultimately provide a more detailed understanding of biological processes, and facilitate the design of artificial nanoscale molecular devices by creating specific microenvironments around active units.5 Porphyrin core dendrimers6 have received special attention due to their potential as hemeprotein mimics for electron transport,6a-f dioxygen binding,6g,h and oxidation catalysis.6i,j The preparation of structurally perfect dendrimers traditionally suffers from its time-consuming nature due to the required repetitive coupling and activation steps, and the necessity for extensive purification. Although accelerated synthetic protocols7 and the construction of less perfect analogs8 have been successfully implemented, the synthesis of highly branched structures having exotic core functionalities remains challenging. Recent advances in the area of “living” ring opening polymerization (ROP) of εcaprolactone9 have enabled the accurate construction of star-shaped polymers.10 We sought to take advantage of this methodology coupled with the space filling branching approach of dendrimer synthesis to achieve site-isolation of porphyrins (Figure 6.1). Our approach is based on the “living” ring opening polymerization of ε-caprolactone using multifunctional, highly branched porphyrin initiators. This very practical and general approach benefits from the rapid synthesis, the ease of purification, and the flexibility of 118
post-modification of both core and chain ends. Due to their convenient synthesis, such functional star polymers represent more practical candidates for novel “smart” materials as compared to their dendritic counterparts.3
Figure 5.1. Site isolation of a porphyrin core using dendrimer (left) or branched star polymer architectures (right).
Results and Discussion Synthesis. Rapid encapsulation of a functional moiety involves the preparation of a low generation hydroxyl-terminated aliphatic polyester dendritic initiator7b,11 for the ring opening polymerization of ε-caprolactone9 to afford the desired functional star polymers (Scheme 5.1). Scheme 5.1 O
O
O
1. esterification 2. deprotection
OH x CORE
O
OH
O
OH
n ROP
O
O(
O) H
O
O(
O) H
n/2x
x
repeat
O
n/2x
x
FUNCTIONAL STAR POLYMER
INITIATOR
core modification
119
chain end modification
The porphyrin-containing initiators 1b and 2b were prepared via esterification of tetrakis(4-hydroxyphenyl)porphyrin (THPP) and tetrakis(3,5-dihydroxyphenyl)porphyrin (TDHPP), respectively, employing acetonide-protected 2,2-bis(hydroxymethyl)-propionic acid,7b followed by deprotection of the diol functionalities under acidic conditions (Scheme 5.2). Scheme 5.2
OH
N
O
O
OH OH
O
O
O
HN
N
HO
OH
O
O
O
O
N
NH
OH
O
THPP
O
N
NH
O O
O
O
HN
DIC, DPTS
O
O
O
OH
HO
NH
N
O
1a
OH
TDHPP
OH
O
OH
O
1b
OH OH
N
HN
NH
N
O
O O
O O
O O
O
O O
2a
O
O
O
HO
N
HN
NH
N
OH O
O
O
O O
HO
OH
O
O O
O
O
OH O
O
HO
O
O
OH
O
HO
O
O O
O
O
HO HO
O
O
O
OH
OH
O
N
NH
2 M H2SO4
O
O
O HO
O
O
O
O HN
HO
HN
(THF, MeOH) O
N
O
O
O
O
HO
N HO
CO2H
(THF, CH2Cl2)
HO
O
O O
O
HO
OH OH
OH HO
OH
2b
Attempts to access other porphyrin-core dendrimers bearing potentially greater number of initiating sites involved the use of a tetrakis(3,4,5-trihydroxyphenyl)porphyrin (TTHPP) core or higher generation dendritic wedges. However, the successfully prepared acetonide-protected dendrimers (Scheme 5.3) could not be deprotected quantitatively without cleavage of the phenolic ester linkages.
120
Scheme 5.3 O
O
O O
O
O
O
O
O
O
O
O
O O
O
O
O O
O O
O
O O O
N
HN
NH
N
O O O
O
O O
O
O O
O
O O
O O
O
O
O
O
O
O
O O
O O
O
O
O
O
3a O
O
O
O
O
O
O O
O
O
O
O
O
O
O
O
O
O
O
N
HN
NH
N
O
O
O
O
O
O
O
O
O
O
O O O O
O
O
NH
N
O
O O O O
O
O
O O
O
O
HN
O
O
O
O
4a
O
O
O
5a
O O O
O O
O
O O
O
O
O
O O O
O
O O O
O
N
O
O
O O
O
O
O
O
O O
O O
O
O
O
O
O
O
O
O
O
O
O O
O
O O
O
O
O
O
O
O
O
O
O
O O O
O
O
O
O O
To complement the spectroscopic measurements on the porphyrin core star polymers as well as to demonstrate the generality of this encapsulation strategy, the pyrene-containing initiators 6b and 7b were prepared from commercially available 1pyrenemethanol (Scheme 5.4). Repetition of the synthetic sequence, consisting of esterification using acetonide-protected 2,2-bis(hydroxymethyl)-propionic acid7b followed by diol deprotection, afforded the first and second generation hydroxyl-terminated dendrimers 6b and 7b in good overall yield The pyrene core is ideally suited for use as a solvatochromic probe since its fluorescence signal is highly sensitive toward the local environment as well as aggregation (excimer formation). 121
Scheme 5.4 O
OH
O
CO2H
O
O
O
O
DIC, DPTS
2 M H2SO4
(THF, CH2Cl2)
(THF, MeOH)
91 %
98 %
6a
O
OH
O
OH
6b
O O
O
O
O
O
O
O
O
O
O
O
CO2H
DIC, DPTS (THF, CH2Cl2) 85 %
2 M H2SO4
O
OH
O
O
OH
O
O
OH
O
OH
(THF, MeOH) 99 %
7a
7b
The corresponding star polymers were prepared from the synthesized initiators by ring opening polymerization of ε-caprolactone. All polymerizations were carried out in the bulk employing catalytic amounts of tin(II) 2-ethylhexanoate, as described in detail by Trollsås and Hedrick.10 The desired polymers12 (Scheme 5.5 and 5.6) were obtained in essentially quantitative yields and narrow polydispersities after a single precipitation into methanol (Table 5.1). Molecular weights (MW) were easily controlled by adjusting the monomer to initiator ratio, in accord with the “living” nature of the polymerization. Increasing degree of polymerization (DP)13 generally required longer polymerization times. Due to the limited solubility of the initiators in the monomer, polymers with DP > 25 were generally prepared most effectively.
122
Scheme 5.5 H (O n/8
O) H n/8 O) H n/16
H (O n/16 O
H (O n/8
)O
O(
O
O
O
H (O n/16 H (O n/16 O) H n/8
O
)O
O
O
)O
O
N
HN
NH
N
H (O n/16
O(
O
O
O(
O
O) H n/16
O( O
O
)O
O
O
O
O
O
N
O
O
O
O
)O
O(
H (O n/16
O
O
O )O
8a-d
O
O O(
O O
O
O) H n/16
O )O
H (O n/16
O) H n/8
O) H n/16
O(
H (O n/16 H (O n/8
O O( O
)O
H (O n/16
O
O
O
N
NH
O
O(
O
HN
O O) H n/8
O) H n/16
O( O
)O H (O n/8
O O O
O )O
O
O
)O O
O) H n/16
O(
)O O
O) H n/16
O(
9a-d
O) H n/16
Scheme 5.6 O O
O( O
O)-H n/4
O
O
O(
O)-H n/4
O
O
O(
O
O( O
O O
O( O
O
O(
O)-H n/2 O)-H n/2
10a-d
11a-d
O
O)-H n/4 O)-H n/4
solvatochromic probe
We focused on porphyrin and pyrene cores due to their unique spectroscopic characteristics that allowed us to probe their microenvironment, and therefore to evaluate the degree of site isolation of the core. The use of THPP and TDHPP having multiple reactive groups offers the advantage of rapidly generating many initiating sites, giving rise to a large number of arms (8 arms for 8a-d12 and 16 arms for 9a-d). To adjust for the smaller number of arms in the pyrene core stars (2 arms for 10a-d and 4 arms for 11a-d), the DP was varied over a wider range.
123
Table 5.1.
Molecular Weight Characteristics of Prepared Functional Star Polymers.
polymer
DP (NMR)
M n (NMR)
M w / M n (GPC)
8a b c d
26.6 33.3 44.6 54.2
25 400 31 600 41 800 50 600
1.14 1.13 1.17 1.19
9a b c d
24.9 31.9 41.0 50.4
47 200 59 900 76 600 93 700
1.18 1.14 1.12 1.10
10a b c d
33.7 56.8 84.5 116.3
8 000 13 300 19 600 26 900
1.35 1.37 1.32 1.26
11a b c d
31.5 53.6 82.4 107.3
14 700 24 800 38 000 49 300
1.21 1.17 1.16 1.18
12a b c d
26.6 33.3 44.6 54.2
25 400 31 600 41 800 50 600
1.14 1.13 1.17 1.19
13a b c d
24.9 31.9 41.0 50.4
47 200 59 900 76 600 93 700
1.18 1.14 1.12 1.10
14a b c d
24.9 31.9 41.0 50.4
50 000 62 700 79 400 96 500
1.18 1.14 1.12 1.10
In order to tune the properties of these materials, further modification of the free base porphyrin core stars was accomplished by metalation of the core moiety as well as by derivatization of the hydroxyl-functional chain ends (Scheme 6.1). Insertion of zinc(II) gave access to zinc porphyrin star polymers 12a-d and 13a-d that were used in fluorescence quenching studies employing an external probe (Scheme 5.7). In contrast, esterification of the polymer chain ends using coumarin-3-carboxylic acid chloride provided star polymers 14a-d having an internal probe since the coumarin chromophores are capable of efficient FRET to the porphyrin core (Scheme 5.8). 124
Scheme 5.7 H (O n/8
O) H n/8 N )O
O
O(
O
H (O n/8
O
2 PF6
H (O n/16
fluorescence quencher
O
)O
O
O
)O
O
N
H (O n/16
N
N
O(
O
O
O(
O
O O
O) H n/16
O(
O
O
O
)O
O(
O
O
O
N
O
O
N
O( O
O
O O
O
N
N
O
O
O
)O
H (O n/16
O) H n/8
O(
O )O O
O
12a-d
O
)O
O O(
O O
O H (O n/16
H (O n/8
O) H n/16
O )O
H (O n/16
O) H n/8
O) H n/16
O(
H (O n/16
O
O O(
O O
O
Zn )O
H (O n/8
O) H n/16
O
)O O
O) H n/16
O
)O O
N Zn
O(
)O O
H (O n/16
O) H n/8 O
O) H n/16
H (O n/16
N
O) H n/16
O(
O) H n/16
13a-d
Scheme 5.8 energy transfer O
O
O
O O O O
O
(O O n/16
O O(
O O
O
O O
N
HN
NH
N
O
O
)O O
O O
O
O O) n/16 O
O O(
O O
O (O n/16 O
O
O
O O
O
O )O
O(
(O n/16
O
O(
O( O
O
O) n/16 O
O
O
)O
O
O( O
O
(O n/16 O
O
O
O
(O n/16 O
O
O( O
O
O
O
O O O) n/16 O
)O
)O
O
O O
)O O
O
O) n/16 O
O
O
(O O n/16
(O O n/16
O
O(
)O
)O
O
O) n/16 O
(O O n/16
O
O) n/16 O O) n/16
O) n/16 O
O O
O O
O O O
14a-d
The polymer modification can easily be monitored using either UV/vis absorption or NMR spectroscopy. The metalation event is conveniently identified characteristic shift
125
of the electronic absorption spectrum in the Q-band region14 (Figure 5.2). Introduction of the coumarin-3-carboxylate dye at each of the 16 hydroxyl chain ends in polymers 14a-d is evident from the additivity of the individual coumarin chromophore units that contribute to the large absorption in the UV region of the spectrum of polymers 14a-d. 1.0
absorbance / a.u.
0.8
x5 0.6
0.4
0.2
500
550
600
650
0.0 300
400
500
600
700
wavelength / nm
Figure 5.2. UV/vis spectra of representative star polymers 9b (_____), 13b (..........), and 14b (-----) in CHCl3.
Furthermore, the 1H NMR spectra of polymers 9a-d and 14a-d reveal a significant downfield shift of the signal associated with the end-groups of 9a-d (-CH2-OH) by conversion to the respective coumarin esters in 14a-d (Figure 5.3). The relative ratio of end-group to methylene polymer peak area is generally used to determine the accurate molecular weight of all polymers (Table 5.1). Please note that a significant advantage of the synthetic route used is that the only purification required after polymerization, metalation, and end-group modification was a precipitation into methanol. All polymers are soluble in a variety of solvents such as CHCl3, THF, or CH3CN.
126
14b
9b
1
Figure 5.3.
H NMR spectra of representative star polymers 9b and 14b in CDCl3.
In addition, dendrimer 15 as well as coumarin-containing model compounds 1618 having no porphyrin acceptor core were prepared as model compounds (Scheme 5.9). Scheme 5.9
O
O
O O
(O O n/6
O
O
O) n/6 O
O O O O
O
O
O
O
O
O
O
N
O
O
O
O O O
O O
O
O
O
O
)O O
O
O
O
O(
O
O )O
O
O(
O O
O O
O (O
O)
n/6
n/6
16
O
O
O
O O O
O
O
O
O
O
O
O O
O
O
O
O O
O
OMe
15
17
127
O
n/6 O
O
O
O
O O
O)
O n/6
O
O
O
O
(O
O
O O
O
O
O
O
O
O
O
O
O
O
O(
O
O
N
)O
O
O
HN
NH
O O
O
O
O O
O
O
O
O
O
O
O
O
O O O
O
O
O O
O
O O
O
O
O
O
18
O
O O
Fluorescence Quenching Experiments. To evaluate the ability of the polyester backbone to effectively isolate the porphyrin moiety, the accessibility of the core in the two zinc porphyrin star polymer series 12a-d and 13a-d was studied using the interaction of a small molecule fluorescence quencher such as methyl viologen with the interior zinc porphyrin moiety (Scheme 5.7). The products of the quenching rate constant kq and the excited state lifetime τ were determined as a function of chain length, i.e. degree of polymerization (DP), using Stern-Volmer analysis15 (Figure 5.4). A direct evaluation of kq to measure core accessibility is possible since the absorption and fluorescence spectra as well as the fluorescence quantum yields (in the absence of the quencher) remain essentially constant, indicating no significant change of τ.16
ZnTPP 15
40
10
30
5
kqτ / M
-1
50
25
20
30
35
40
45
50
55
10
0
10
20
30
40
50
degree of polymerization Figure 5.4. Fluorescence quenching for two series of zinc porphyrin core star polymers and having 8 arms, 12b (!), and 16 arms, 13b (#). Zinc tetraphenylporphyrin (ZnTPP) is shown as a reference. The kqτ values are derived from Stern-Volmer analysis in acetonitrile employing methyl viologen as the quencher.
A strong shielding of the core moiety in the star polymers compared to zinc tetraphenylporphyrin (ZnTPP) as the reference was observed, thereby demonstrating 128
inhibited penetration of the small molecule quencher through the polymeric backbone. The magnitude of site isolation is significantly higher than in the dendritic counterparts employed in similar quenching studies.6e,k The degree of shielding is clearly dependent on the chain length: with increasing DP the accessibility of the core decreases. Extrapolation suggests a rather steep decline in core accessibility in the early stages where DP is less than 25. Surprisingly, the quenching efficiency is comparable for 8-arm and 16-arm stars having similar DPs, suggesting that the chain length, rather than the number of arms, is crucial for isolation of the core unit. This finding is in agreement with existing experimental studies17 as well as theoretical models describing the shape of star polymers using an asphericity factor δ that has a value of 1 for cylindrical molecules and vanishes for molecules with spherical symmetry.18 In good solvents, only minor differences are predicted between the 8-arm star (δ = 0.14)19 and 16-arm star (δ = 0.07), and this difference is expected to be diminished even further in poor solvents,20 such as the acetonitrile employed in this experiment. However, the fluorescence quenching experiments were somewhat limited due to the low solubility of the external probe in the less polar solvents that are good solvents for the investigated polymers. Rather than employing different neutral quenchers,6k,q we sought to take advantage of the unique design of the system with its multiple reactive chain ends to attach an internal probe enabling the study of site isolation as a function of solvent. FRET Studies. FRET involves the non-radiative transfer of singlet excitation energy from a donor chromophore to an acceptor chromophore. According to Förster’s mechanism,21a the magnitude of the interaction, i.e. the FRET efficiency (ΦFRET), is 129
inversely proportional to the sixth power of the donor-acceptor separation.15,21 Mainly due to this sensitive distance dependence, FRET has proven to be an exceptional tool for the study of the conformation and motion of biological macromolecules.22 In order to monitor interactions over the range of several nanometers, a high intrinsic probability of FRET and therefore maximized spectral overlap between the emission of the donor and the absorption of the acceptor is required.15,21 In the present study, the porphyrin core served as acceptor, whereas multiple donors were introduced by modification of the chain ends (Scheme 5.8). In our system, coumarin-3-carboxylates were chosen as the donor chromophores since their emission, centered around 420 nm, strongly overlaps with the Soret absorption band (λmax = 420 nm) of the porphyrin acceptor core (Figure 5.5). To our knowledge, this is the first time the emission originating from a coumarin dye is quenched by the porphyrin Soret absorption.23 In addition, coumarin-3-carboxylic acid is a commercially available, rather inexpensive dye that can be conveniently linked to the hydroxyl-chain ends via esterification. When the coumarin donors in polymers 14a-d were excited selectively (λexc = 350 nm), emission from both the coumarins and the porphyrin acceptor was observed, demonstrating that FRET was facile but not quantitative in this system. In a separate control experiment, excitation of the porphyrin core star polymers 9a-d having no coumarin donor chromophores attached led to no observable emission due to the negligible absorption at this particular excitation wavelength. It is important to note that at concentrations above 0.2 µM, the extremely high extinction coefficient of the Soret band (ε = 519,000 M-1cm-1) promotes self-absorption, i.e. trivial radiative energy transfer. 130
Since the coumarin emission spectrum is very indicative of this effect, it could be shown that the portion of the radiative energy transfer increased linearly with increasing concentration and therefore optical density, assuming constant efficiency of the nonradiative transfer, i.e. FRET. In all experiments concentrations of approximately 0.1 µM were employed to avoid this self-absorption process, and to enable the use of both good and poor solvents in the experiments. Based on the very low concentrations employed, aggregation phenomena are unlikely to occur. Further experimental evidence for this assumption arises from the excellent agreement of the MW determined independently by light scattering, 1H-NMR as well as the constant gel permeation chromatography (GPC) elution volume of polymers 14a-d within a wide concentration range (10-8 – 10-4 M in THF and CHCl3). The exclusion of aggregation is essential since only intramolecular FRET provides valuable information about the intrinsic polymer dynamics. porphyrin absorption
coumarin absorption
corrected fluorescence intensity / a.u.
0
1
absorbance
2
3
exc 300
coumarin emission
400
500
porphyrin emission
4
600
wavelength / nm
Figure 5.5. Photophysical characteristics of compounds 14a-d in chloroform. Increasing optical density (concentration = 0.2 – 4 µM) of the sample (top) leads to enhanced self-absorption (trivial energy transfer) in the system as indicated by the shape of the donor emission spectrum (bottom).
131
The dependence of FRET on polymer chain length was investigated (Figure 5.6). As the chain length increases and the donor chromophores are placed at further average distances from the acceptor core, the donor emission intensity increases as the result of the reduced probability of FRET in the system. In one extreme case, quantitative FRET is observed in dendrimer 15 due to extremely short average donor-acceptor distances. In contrast, no FRET occurs in model compound 16 as a result of the absence of an acceptor
corrected fluorescence intensity / a.u.
chromophore.
16 (no acceptor) 14a (DP=50) 14b (DP=41) 14c (DP=32) 14d (DP=25) 15 (DP=0)
400
450
wavelength / nm
500
550
Figure 5.6. Corrected emission of the terminal coumarin donor chromophores in compounds 14a-d and model compounds 15 and 16 in chloroform as a function of chain length (DP).
The values of ΦFRET were determined by the method of quenched donor emission,24 which compares the coumarin emission in the presence of the acceptor (14ad and 15) to the emission in the absence of an acceptor, as in model compound 16. Almost identical results were obtained using different model compounds such as 17 or 18. The results shown in Figure 5.7 obtained with different solvents reflect the chain length dependence, as described above, and complement our earlier findings using 132
fluorescence quenching (vide supra). Interestingly, a pronounced solvent effect is observed. In good solvents for the poly(ε-caprolactone) stars, such as CHCl3 or toluene, a steep decline of ΦFRET is observed with increasing DP, whereas in poor solvents such as acetonitrile or DMSO, ΦFRET levels off at high DP. Although other coumarins such as 7methoxycoumarin display solvent dependent emission characteristics,25 the observed effect is clearly due to conformational changes since the chain length is the only variable for measurements in each solvent.
energy transfer efficiency / %
100
DMSO acetonitrile chloroform toluene
90 80 70 60 50 40 0
10
20
30
degree of polymerization
40
50
Figure 5.7. Resonance energy transfer from the terminal coumarin donor chromophores to the free base porphyrin core acceptor in star polymers 14a-d and dendrimer 15 employing different solvents. The energy transfer efficiencies were determined from the amount of quenched donor emission as compared to model compound 16.
We suggest that the collapse of star polymers 14a-d in poor solvents leads to a reduced average donor-acceptor distance and therefore increased ΦFRET as compared to the extended conformations present in good solvents (Figure 5.8).26 In a crude approximation, the different slopes in Figure 5.7 can be rationalized by considering a sphere (δ = 0.07, vide supra) for which the volume is directly related to the third power of the radius, i.e. V ∝ r3. By progressing outward and assuming a similar density, the same 133
changes in volume will be associated with smaller and smaller changes in radius. This behavior should be most pronounced in the solvent collapsed and therefore more densely packed structure since an increase in DP will have only a minor effect on the average donor-acceptor separation.
Figure 5.8. Illustration of the solvation induced encapsulation of the core functionality. While the polymer adopts a more extended conformation in a good solvent (left), it collapses in a poor solvent (right) leading to a reduced average donor-acceptor distance and therefore enhanced energy transfer efficiency.
Recent work on dendritic systems with nearly quantitative ΦFRET (ΦFRET = 0.93 – 0.98) related interchromophoric distances estimated from molecular modeling to the rate of FRET measured by time-resolved techniques.24a In contrast, the star polymer counterparts studied here cover a much wider range of donor-acceptor distance and therefore ΦFRET (ΦFRET = 0.46 – 0.98). In the special case when ΦFRET is 0.5, the corresponding distance known as the Förster radius R0 can be calculated from the spectral overlap of the participating chromophores.21 Since theory validates the assumption that, in the absence of any favorable interactions between chain ends and inner building blocks,1e the terminal groups are located near the periphery,27 this allows a rough
134
correlation of molecular size with measured ΦFRET. For this particular system, R0 is calculated to be 8.6 nm using eq 1,
R0 = 6
0.5291κ 2 J n 4NA
(1)
where κ2 is the orientation factor, J is the overlap integral of the fluorescence intensity of the donor and the molar extinction coefficient of the acceptor normalized by the frequency expressed in wavenumbers, n is the index of refraction of the solvent, and NA is Avogadro’s constant.15b This suggests a diameter of 14d in CHCl3 or toluene in the order of 18-20 nm. This value provides a reasonable explanation of why our attempts to directly obtain molecular size data by light scattering were not successful, since reliable data can usually only be obtained if the diameter of the investigated molecule is at least 1/20 of the wavelength of the laser (488 nm) used, i.e. at least 25 nm.28
PGSE NMR Experiments. In addition to its conventional role of providing detailed information about the local electronic environment of a molecule, NMR also represents a powerful tool for the study of overall molecular properties. Since sizes and shapes of molecular objects are related to friction factors for reorientational and translational motion, a correlation with nuclear relaxation rates is possible. Translational motion can effectively be studied by NMR using PGSE methods,29 relating signal intensities to diffusion rates and therefore enabling the resolution of molecular dimensions in solution. With regard to non-biological macromolecules, PGSE NMR has mainly been applied to the study of surfactant systems and polymer mixtures.29b Surprisingly in view of its great potential, the use of this method to study branched polymer architectures has so far been 135
rather limited.30 In our case, PGSE NMR represents an ideal opportunity to study the effect of chain length as well as solvent on the actual size of the star polymers. When a pulse sequence producing a spin echo is repeated under conditions of increasing gradient strength, the observed signal intensities will decrease depending on the diffusion rate of the corresponding spin-labeled species. In this process the gradient encodes the spatial location of the observed molecule, similar to magnetic resonance imaging (MRI). Employing such experimental setup, star polymers 14a-d were measured in CDCl3 and CD3CN, respectively. Figure 5.9 shows two representative 2D NMR spectra, displaying chemical shift in one dimension and gradient strength, which is correlated to molecular diffusion and therefore size, in the other dimension. Depending on the solvent, the same polymer sample exhibits a distinctly different decay behavior. As a result of a larger diffusion coefficient, which in turn has its origin in a smaller size of the diffusing object, decay is faster in a bad solvent (CD3CN) than in a good solvent (CDCl3). Quantitative analysis was accomplished by linear regression of the StejskalTanner equation31 (eq 2), I = I0e
(
)
g 2γ 2δ2 ∆ − δ D 3
(2)
where g is the gradient strength, γ is the gyromagnetic ratio, δ is the duration of gradient pulse, ∆ is the delay between consecutive gradient pulses, and D is the diffusion coefficient (Figure 5.10). Although the investigated system is not monodisperse, satisfactory data (R > 0.99) were obtained using a linear regression procedure.
136
Presumably, the low polydispersity (PDI = 1.10 - 1.20) and the high sphericity contribute to a narrow diffusion coefficient distribution.32
CDCl3
CD3CN
4.0
3.5 1H
3.0
2.5
2.0
g
1.5
n ie d ra
th ng e tr ts
chemical shift (ppm)
Figure 5.9. Stacked plot of 1H NMR spectra of star polymer 14b in CDCl3 (top) and CD3CN (bottom) acquired with increasing gradient strength at 298 ± 1 K. 0.0
chloroform
-0.2
14d 14c 14b 14a
-0.4
ln (I/I0)
-0.6 -0.8
14d
-1.0 -1.2
14c
-1.4
14b
-1.6
acetonitrile
-1.8 0
1
2
3 2 2 2
4
5 9
14a 6
2
g γ δ (∆-δ/3) (10 s/m ) Figure 5.10. Plot of polymer peak area versus g2γ2δ2(∆-δ/3) and linear fit for star polymers 14a-d in CDCl3 (open symbols, dotted lines) and CD3CN (solid symbols, solid lines) at 298 ± 1 K.
137
From the obtained diffusion coefficients, the hydrodynamic radii RH were estimated using the Stokes-Einstein equation (eq 3), RH =
k BT 6πηD
(3)
where kB is the Boltzmann constant, T is the absolute temperature, and η is the viscosity of the solvent. The results clearly reflect the dependence of size and therefore siteisolation on chain length and solvent (Table 5.2). In both solvents the increasing DP corresponds to an increase in RH giving rise to a “thicker” polymer shell around the core. In comparison to the good solvent, the poor solvent leads to largely reduced sizes indicating a collapse of the poly(caprolactone) backbone around the core unit leading to a more densely packed shell. These results are in good agreement with the FRET studies described above. For instance the RH and ΦFRET values of 14a in CDCl3 and 14d in CD3CN are comparable. Furthermore, the size of 14d in CDCl3 as measured by PGSE NMR agrees well with the calculated Förster radius (vide supra) validating the assumption that the terminal ends are close to the periphery in the investigated polymer architectures. Table 5.2.
Diffusion Coefficients D and Hydrodynamic Radii RH of star polymers 14a-d in CDCl3 and CD3CN at 298 ± 1 K.
solvent
polymer
D (m2/s)
RH (nm)
CDCl3
14a b c d
8.62 x 10-11 7.31 x 10-11 5.86 x 10-11 4.40 x 10-11
4.7 5.5 6.9 9.2
CD3CN
14a b c d
3.20 x 10-10 2.36 x 10-10 1.85 x 10-10 1.39 x 10-10
2.0 2.7 3.4 4.6
138
In addition, the theoretical maximum radius assuming a fully extended conformation was estimated using molecular modeling that predicts a length of ∼ 8.6 Å for each monomer repeat unit. Therefore, polymer 14d (DP = 50) would have a theoretical maximum radius of approximately 44 nm, i.e. 50 x 8.6 Å + ½ core size (∼ 10 Å). Not unexpectedly, the measured radius of 9.2 nm (Table 5.2) is much smaller, presumably due to substantial participation of random coil conformations. Solvatochromic Probes. In an alternative approach to study core isolation that does not involve porphyrin chromophores, star polymers 10a-d and 11a-d with a pyrene core were investigated as solvatochromic probes of their own core environment. Pyrene itself has been used extensively to help determine local environments since the vibrational fine structure of its fluorescence spectrum, namely the ratio of the I1 peak (0-0 band) and the I3 peak (0-2 band), is very sensitive to solvent polarity due to vibronic coupling (Ham effect).33 With increasing polarity of the probe’s microenvironment, the I1:I3 ratio increases since the I1 band is markedly enhanced whereas the I3 band remains unaffected. In addition, pyrene can be used to study aggregation phenomena due to its characteristic excimer emission.34 As expected, when substitution is introduced in order to attach the initiating functional groups, the pyrene moiety becomes less sensitive to changes in solvent polarity. The decreased probe sensitivity is not a result of the lowered symmetry of the system, but instead it derives from the introduction of the nearby carbonyl functionality, which presumably interferes with the vibronic coupling mechanism. This can be shown by a comparison of the changes in I1:I3 ratio (∆I1:I3) when going from acetonitrile to CHCl3: for pyrene ∆I1:I3 ≈ 0.5, for initiators 6b and 7b: ∆I1:I3 ≈ 0.1, whereas for 1139
pyrenemethanol ∆I1:I3 ≈ 0.6. The substitution pattern also prevents excimer formation, since even at relatively high concentrations of approximately 0.5 mM no excimer emission could be detected. However, when solvents such as toluene and DMSO were employed, representing extremes in polarity, a clear trend could be deduced from the I1:I3 ratios (Figure 5.11).
I1 : I3 fluorescence intensity ratio
2.6
DMSO:
10
11
toluene:
10
11
2.5
2.4
2.3 0
20
40
60
80
degree of polymerization
100
120
Figure 5.11. Solvatochromic probing using the I1:I3 fluorescence intensity ratio in two series of pyrene core star polymers having 2 arm (10a-d) and 4 arms (11a-d) in toluene and DMSO.
In agreement with the experiments described above, a significant chain length dependence on core isolation is found. With increasing DP, the local environment around the core approaches a polarity reflecting that of the poly(ε-caprolactone) shell, which is more polar than toluene but less polar than DMSO. As observed with the FRET measurements (Figure 4), the response to a change in chain length is more pronounced in the good solvent, providing further evidence in support of solvation-induced site encapsulation. Furthermore, the change in the number of arms, going from 10a-d to 11ad (2 vs 4 arms), contributes more to site isolation than the change from 12a-d to 13a-d (8 vs 16 arms), especially when the polymer is extended (good solvent). This is not 140
surprising since the shape differences (∆δ)18 between the 2-arm star (δ = 0.53)19 and the 4-arm star (δ = 0.27) are more pronounced than those for the 8-arm star (δ = 0.14) and 16arm star (δ = 0.07), recalling that δ = 0 for a sphere (vide supra).
Conclusions The construction of star polymers via ring opening polymerization of εcaprolactone using functional dendritic initiators has been demonstrated to be an efficient route for the encapsulation of active core functionalities. While this approach lacks the precision of dendrimer encapsulation,3 it is synthetically simpler providing access to a larger range of sizes and allowing the products to be easily purified by precipitation. Moreover, this route seems to be fairly general, since in principle any functional core carrying phenol or alcohol functionalities (or conceivably amines) could be encapsulated using similar chemistry. The possibility of post-modification affords access to a wide variety of materials that may be used to probe the effect of variables such as chain length, number of arms, or solvent on core isolation. Using three different types of assays, namely fluorescence quenching, FRET, and solvatochromic probes, it has been shown that core encapsulation is mainly dependent on DP with only minor contributions arising from the number of arms. In addition, poor solvents seem to further increase the degree of site isolation due to a structural collapse of the polymer backbone giving rise to a more dense shielding around the core unit. This solvation-induced encapsulation effect and the chain length dependence are supported by PGSE NMR experiments that allow for direct determination of the molecular sizes of the polymers in different solvents. FRET as well as PGSE NMR have been shown to be particularly useful techniques to study the 141
dynamics of star polymers in solution. These studies concerned with the general principles of site-isolation and its practically useful realization will ultimately lead to the design of future functional materials.
Experimental General Methods: All reagents were used as received and without further purification, unless otherwise noted. THF was distilled under N2 over sodium/benzophenone prior to use.
ε-Caprolactone
(99%)
was
distilled
over
CaH2.
Isopropylidene-2,2-
bis(methoxy)propionic acid, its second generation analog (acetonide)2[G-2]CO2H, and benzyl 2,2-bis(hydroxymethyl)propionate were prepared as described in the literature.7b Tetrakis(4-hydroxyphenyl)porphyrin (THPP), tetrakis(3,5-dihydroxyphenyl)porphyrin35 (TDHPP), tetrakis(3,4,5-trihydroxyphenyl)porphyrin36 (TTHPP, as its dihydrobromide salt) were prepared from pyrrole and the respective aromatic aldehydes as their methyl ethers using Adler-Longo condensation conditions37 followed by boron tribromide deprotection.38 Coumarin-3-carboxylic acid chloride was prepared prior to use from coumarin-3-carboxylic acid using oxalyl chloride and catalytic amounts of DMF in CH2Cl2. Methyl viologen hexafluorophosphate was prepared from the commercially available dibromide salt via anion exchange using potassium hexafluorophosphate by mixing saturated solutions of both salts followed by filtration and thorough washing with water. Column chromatography was carried out with Merck silica gel for flash columns, 230-400 mesh. Absorption spectra were recorded on a Cary 50 UV-Visible Spectrophotometer and a Hewlett-Packard 8453 diode array spectrophotometer, respectively. GPC measurements were performed on a Waters 150CV plus GPC system 142
equipped with a differential refractive index detector and a M486 UV detector (254 nm detection wavelength) using THF as the mobile phase at 45 oC and a flow rate of 1 mL/min. The samples were separated through four 5 µm PL Gel columns (Polymer Laboratories) with porosities of 100 Å, 500 Å, 1000 Å and mixed C. The columns were calibrated with 18 narrow polydispersity polystyrene samples. For the light scattering measurements, a system consisting of a Waters M590 solvent delivery system equipped with an OPTILAB DSP interferometric refractometer, a DAWN DSP laser photometer (488 nm laser wavelength) with 488 ±1 nm UV filters on detectors 7, 9, and 11, dn/dc, and Wyatt’s Astra software was used. Separation was achieved in THF or CHCl3 on a set of two Polymer Standard SVD linear columns (8 x 300 mm, 5 µm) at 45 oC and 1.0 ml/min flow rate. MALDI-TOF mass spectra were measured on a Perseptive Biosystems Voyager-DE spectrometer in delayed extraction mode and an acceleration voltage of 20 keV. Samples were prepared using a 1:20 ratio of analyte (5 mg/mL in THF) to matrix solution (trans-indoleacrylic acid, 10 mg/mL in THF). NMR Spectroscopy. NMR spectra were recorded on Bruker AMX 300 (300 MHz) or Bruker DRX-500 (500 MHz) instruments with TMS as internal standard. The number average molecular weights of the polymers were calculated from the ratio of the CH2O methylene proton signals (δ = 4.06 ppm) and the CH2OH methylene proton signals (δ = 3.65 ppm) in the 1H NMR spectra. PGSE NMR experiments were carried out on a Bruker DRX 500 (500 MHz) spectrometer equipped with a microprocessor-controlled gradient unit and a 5 mm multinuclear probe. A BPP-LED pulse sequence39 (Bruker’s pulse program “ledbpgs2s”) with a gradient pulse width δ = 3 ms and a delay between the gradient pulses ∆ = 100 ms was used. The gradient strength g was calibrated using the 143
diffusion coefficient of HDO in D2O as a reference.40 Measurements were performed at 298±1 K in CDCl3 and CD3CN, respectively (~ 0.1 mM polymer concentrations). Linear fitting (R > 0.99) according to the Stejskal-Tanner equation:31 ln(I/I0) = g2γ2δ2(∆-δ/3)D using the individual polymer peak areas of the FT-NMR spectra gave the diffusion coefficients D, from which the hydrodynamic radii RH were derived using the StokesEinstein equation: RH = (kBT)/(6πηD), with η298K(CHCl3) = 0.542 mPas and η298K(CH3CN) = 0.345 mPas. Emission Spectroscopy. Fluorescence spectra were measured of degassed solutions (1cm cells, ODmax < 0.1) using an ISA/SPEX Fluorolog 3.22 equipped with a 450 W Xe lamp, double excitation and double emission monochromators, and a digital photon-counting photomultiplier. The coumarin-3-carboxylate-containing samples 14a-d and 15-18 were excited at 350 nm, slit widths were set to 2 nm bandpass for excitation and 5 nm bandpass for emission. Correction for variations in lamp intensity over time and wavelength was achieved with a solid-state silicon photodiode as the reference. The spectra were further corrected for variations in photomultiplier response over wavelength and for the path difference between the sample and the reference by multiplication with emission correction curves generated on the instrument. For the fluorescence quenching experiments, a solution of methyl viologen hexafluorophosphate in acetonitrile was applied as the quencher and varied over a concentration range between 5-20 mM. The ratios of the fluorescence quantum yields were calculated from the integration of the emission spectra. The Stern-Volmer analysis was performed according to standard procedures.15 The quantum yields for energy transfer were calculated from the ratio of the integrated, for absorbance corrected emission spectra of 14a-d as well as 15 and model 144
compound 16. To determine the I1:I3 ratio, pyrene core stars 10a-d and 11a-d were excited at 345 nm, and slit widths were set to 0.5 nm for both excitation and emission.
General Procedure for Preparation of Acetonides 1a, 2a, 3a, 4a, 5a, 6a, 7a: 1 Equiv. of the polyol core was dissolved in the minimum amount of dry THF, 1.2 equiv. of isopropylidene-2,2-bis(methoxy)propionic acid7b per hydroxyl group and 0.2 equiv. of 4dimethylaminopyridinium tosylate (DPTS) per phenolic group were added. Then, a ∼ 1.5 M solution of 1.2 equiv. 1,3-diisopropylcarbodiimide per phenolic group in CH2Cl2 was added and it was stirred overnight. The completion of the reaction was conveniently followed by MALDI-TOF mass spectrometry. The reaction mixture was filtered through a glass filter, the residue rinsed with a small amount of CH2Cl2, and the filtrate evaporated in vacuo. Flash chromatography (silica gel, linear gradient from 100 % hexanes to ethyl acetate/hexanes mixtures) gave the desired products.
1a: This was prepared as above from THPP and isopropylidene-2,2-bis(methoxy)propionic acid (85 % yield). 1H NMR (300 MHz, CDCl3, 25 °C, TMS): δ 8.89 (broad s, 8 H, β-H), 8.24 (d, 3J (H,H) = 9 Hz, 8 H, Ar-H), 7.53 (d, 3J (H,H) = 9 Hz, 8 H, Ar-H), 4.52 (d, 2J (H,H) = 12 Hz, 8 H, OCH2), 3.91 (d, 2J (H,H) = 12 Hz, 8 H, OCH2), 1.55 (s, 24 H, CH3), 1.50 (s, 12 H, CH3), -2.81 (broad s, 2 H, NH); MALDI-TOF MS (trans-3indoleacrylic acid matrix): m/z = 1303 (calcd for C76H78N4O16+ 1302); Anal. C: 69.89, H: 5.94, N: 4.17 (calcd C: 70.03, H: 6.03, N: 4.30).
145
2a: This was prepared as above from TDHPP and isopropylidene-2,2-bis(methoxy)propionic acid (88 % yield). 1H NMR (300 MHz, CDCl3, 25 °C, TMS): δ 9.00 (broad s, 8 H, β-H), 7.86 (d, 4J (H,H) = 3 Hz, 8 H, Ar-o,o’-H), 7.43 (t, 4J (H,H) = 3 Hz, 4 H, Ar-pH), 4.40 (d, 2J (H,H) = 12 Hz, 16 H, OCH2), 3.81 (d, 2J (H,H) = 12 Hz, 16 H, OCH2), 1.46 (s, 24 H, CH3), 1.41 (broad s, 48 H, CH3), -2.99 (broad s, 2 H, NH); MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 1992 (calcd for C108H126N4O32+ 1992); Anal. C: 65.28, H: 6.49, N: 2.80 (calcd C: 65.11, H: 6.37, N: 2.81).
3a: This was prepared as above from TTHPP and isopropylidene-2,2-bis(methoxy)propionic acid (53 % yield). 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 9.07 (broad s, 8 H, β-H), 7.92 (s, 8 H, Ar-H), 4.47 (d, 2J (H,H) = 12 Hz, 8 H, OCH2), 4.34 (d, 2J (H,H) = 12 Hz, 16 H, OCH2), 3.89 (d, 2J (H,H) = 12 Hz, 8 H, OCH2), 3.76 (d, 2J (H,H) = 12 Hz, 16 H, OCH2), 1.64 (s, 12 H, CH3), 1.54 (s, 12 H, CH3), 1.52 (s, 12 H, CH3), 1.41 (s, 24 H, CH3), 1.39 (s, 24 H, CH3), 1.33 (s, 24 H, CH3), -3.04 (broad s, 2 H, NH); MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 2680 (calcd for C140H174N4O48+ 2681); Anal. C: 62.58, H: 6.70, N: 2.04 (calcd C: 62.72, H: 6.54, N: 2.09).
4a: This was prepared as above from THPP and (acetonide)2[G-2]CO2H (76 % yield). 1
H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 8.88 (broad s, 8 H, β-H), 8.23 (d, 3J (H,H) =
9 Hz, 8 H, Ar-H), 7.54 (d, 3J (H,H) = 9 Hz, 8 H, Ar-H), 4.68 (d, 2J (H,H) = 13 Hz, 8 H, OCH2), 4.64 (d, 2J (H,H) = 13 Hz, 8 H, OCH2), 4.31 (d, 2J (H,H) = 12 Hz, 16 H, OCH2), 3.74 (d, 2J (H,H) = 12 Hz, 16 H, OCH2), 1.64 (s, 12 H, CH3), 1.46 (s, 24 H, CH3), 1.44 (s, 24 H, CH3), 1.26 (s, 24 H, CH3), -2.83 (broad s, 2 H, NH); MALDI-TOF MS (trans-3146
indoleacrylic acid matrix): m/z = 2392 (calcd for C128H158N4O40+ 2393); Anal. C: 63.98, H: 6.47, N: 2.38 (calcd C: 64.26, H: 6.66, N: 2.34).
5a: This was prepared as above from TDHPP and (acetonide)2[G-2]CO2H (72 % yield). 1
H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 8.98 (broad s, 8 H, β-H), 7.93 (d, 4J (H,H) =
2 Hz, 8 H, Ar-o,o’-H), 7.45 (t, 4J (H,H) = 2 Hz, 4 H, Ar-p-H), 4.55 (d, 2J (H,H) = 11 Hz, 16 H, OCH2), 4.51 (d, 2J (H,H) = 11 Hz, 16 H, OCH2), 4.14 (d, 2J (H,H) = 11 Hz, 32 H, OCH2), 3.56 (d, 2J (H,H) = 11 Hz, 32 H, OCH2), 1.51 (s, 24 H, CH3), 1.16 (s, 48 H, CH3), 1.11 (s, 48 H, CH3), 1.09 (s, 48 H, CH3), -2.96 (broad s, 2 H, NH); MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 4170 (calcd for C212H286N4O80+ 4171); Anal. C: 61.07, H: 6.80, N: 1.42 (calcd C: 61.05, H: 6.91, N: 1.34).
6a: This was prepared as above from 1-pyrenemethanol and isopropylidene-2,2bis(methoxy)propionic acid (91 % yield). 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 8.26-7.99 (m, 9 H, Ar-H), 5.89 (s, 2 H, ArCH2O), 4.22 (d, 2J (H,H) = 12 Hz, 2 H, CH2O), 3.64 (d, 2J (H,H) = 12 Hz, 2 H, CH2O), 1.41 (s, 3 H, CH3), 1.39 (s, 3 H, CH3), 1.15 (s, 3 H, CH3);
13
C NMR (125 MHz, CDCl3): 174.2, 131.7, 131.2, 130.7, 129.4, 128.7, 128.1,
127.8, 127.6, 127.3, 126.1, 125.5, 125.4, 124.9, 124.6, 124.5, 122.9, 98.1, 66.0, 65.3, 42.1, 24.7, 22.6, 18.6; Anal. C: 77.43, H: 6.31 (calcd C: 77.30, H: 6.23).
7a: This was prepared as above from 6b and isopropylidene-2,2-bis(methoxy)propionic acid (85 % yield). 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 8.31-8.01 (m, 9 H, Ar-H), 5.90 (s, 2 H, ArCH2O), 4.32 (dd, 2J (H,H) = 17Hz, 2J (H,H) = 12 Hz, 4 H, CH2O), 3.98 147
(ddd, 2J (H,H) = 17Hz, 2J (H,H) = 12 Hz, 3J (H,H) = 2 Hz, 4 H, CH2O), 3.44 (d, 2J (H,H) = 12 Hz, 3J (H,H) = 2 Hz, 4 H, CH2O), 1.32 (s, 3 H, CH3), 1.28 (s, 3 H, CH3), 1.26 (s, 3 H, CH3), 0.93 (s, 3 H, CH3);
13
C NMR (125 MHz, CDCl3): 173.44, 172.48, 131.88,
131.14, 130.65, 129.59, 128.38, 128.31, 127.93, 127.90, 127.27, 125.56, 125.52, 124.89, 124.61, 124.52, 122.68, 97.97, 65.81, 65.74, 65.50, 65.32, 47.01, 41.88, 24.87, 22.09, 18.26, 17.67; Anal. C: 69.55, H: 7.00 (calcd C: 69.07, H: 6.71).
General Procedure for Preparation of Polyols 1b, 2b, 6b, 7b: The respective acetonides were dissolved in the minimum amount of THF, some methanol added, and 2 M H2SO4 (∼ 1 ml per 0.1 mmol of acetonide group). It was stirred at room temperature and the reaction followed by MALDI-TOF mass spectrometry. After complete deprotection, 7 M ammonia in methanol was added to adjust to a basic pH. The solvent was removed in vacuo, the resulting residue dissolved in THF, filtered, and evaporated to afford the free alcohols.
1b: This was prepared as above from 1a (96 % yield). 1H NMR (300 MHz, DMSO-d6, 25 °C, TMS): δ 8.89 (broad s, 8 H, β-H), 8.25 (d, 3J (H,H) = 9 Hz, 8 H, Ar-H), 7.55 (d, 3J (H,H) = 9 Hz, 8 H, Ar-H), 5.12 (broad s, 8 H, OH), 3.88 (d, 2J (H,H) = 12 Hz, 8 H, OCH2), 3.72 (d, 2J (H,H) = 12 Hz, 8 H, OCH2), 1.39 (s, 12 H, CH3), -2.90 (broad s, 2 H, NH); MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 1143 (calcd for C64H62N4O16+ 1143); Anal. C: 67.40, H: 5.45, N: 4.85 (calcd C: 67.24, H: 5.47, N: 4.90); UV/vis (MeOH) λmax (ε) 270 nm (60000), 414 nm (498000), 512 nm (18800), 546 nm (8700), 588 nm (5600), 644 nm (3800). 148
2b: This was prepared as above from 2a (97 % yield). 1H NMR (300 MHz, DMSO-d6, 25 °C, TMS): δ 8.98 (broad s, 8 H, β-H), 7.89 (d, 4J (H,H) = 3 Hz, 8 H, Ar-o,o’-H), 7.43 (t, 4
J (H,H) = 3 Hz, 4 H, Ar-p-H), 4.95 (broad s, 16 H, OH), 3.75 (d, 2J (H,H) = 12 Hz, 16 H,
OCH2), 3.56 (d, 2J (H,H) = 12 Hz, 16 H, OCH2), 1.27 (s, 24 H, CH3), -3.03 (broad s, 2 H, NH); MALDI-TOF MS (trans-3-indoleacrylic acid matrix): m/z = 1671 (calcd for C84H94N4O32+ 1672); Anal. C: 60.75, H: 5.49, N: 3.43 (calcd C: 60.35, H: 5.67, N: 3.35); UV/vis (MeOH) λmax (ε) 270 nm (129000), 415 nm (522000), 512 nm (22700), 545 nm (7900), 587 nm (6800), 644 nm (3300).
6b: This was prepared as above from 6a (98 % yield). 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 8.27-7.99 (m, 9 H, Ar-H), 5.89 (s, 2 H, ArCH2O), 3.92 (dd, 2J (H,H) = 12 Hz, 3J (H,H) = 6 Hz, 2 H, CH2O), 3.71 (dd, 2J (H,H) = 12 Hz, 3J (H,H) = 6 Hz, 2 H, CH2O), 2.86 (t, 3J (H,H) = 6 Hz, 2H, OH), 1.03 (s, 3 H, CH3);
13
C NMR (125 MHz, CDCl3):
175.8, 131.8, 131.2, 130.6, 129.5, 128.3, 128.3, 127.9, 127.7, 127.3, 126.1, 125.6, 125.5, 124.9, 124.6, 124.6, 122.6, 68.5, 65.6, 49.4, 17.1; Anal. C: 75.68, H: 5.66 (calcd C: 75.84, H: 5.79); UV/vis (CHCl3) λmax (ε) 267 nm (24500), 278 nm (44200), 315 nm (11700), 329 nm (27600), 345 nm (40500).
7b: This was prepared as above from 7a (99 % yield). 1H NMR (500 MHz, DMSO-d6, 25 o
C, TMS): δ 8.35-8.08 (m, 9 H, Ar-H), 5.87 (s, 2 H, ArCH2O), 4.64 (t, 2J (H,H) = 5 Hz, 4
H, OH), 4.18 (dd, 2J (H,H) = 12 Hz, 3J (H,H) = 11 Hz, 4 H, CH2O), 3.46 (dd, 2J (H,H) = 11 Hz, 3J (H,H) = 5 Hz, 4 H, CH2O), 3.41 (dd, 2J (H,H) = 11 Hz, 3J (H,H) = 5 Hz, 4 H, 149
CH2O), 1.22 (s, 3 H, CH3), 0.97 (s, 6 H, CH3); 13C NMR (125 MHz, DMSO-d6): 174.07, 172.33, 131.11, 130.66, 130.17, 128.86, 128.84, 128.04, 127.67, 127.60, 127.26, 126.36, 125.55, 125.48, 124.64, 123.94, 123.73, 122.97, 64.95, 64.91, 63.69, 50.25, 46.50, 17.18, 16.63; Anal. C: 66.38, H: 6.41 (calcd C: 66.20, H: 6.25); UV/vis (CHCl3) λmax (ε) 267 nm (24600), 278 nm (44800), 315 nm (11800), 329 nm (28400), 345 nm (41600).
General Procedure for Preparation of Starpolymers 8a-d, 9a-d, 10a-d, 11a-d: A procedure similar to the one reported by Trollsås, Hedrick, and coworkers was used.10 The carefully dried initiators 1b, 2b, 6b, 7b were dissolved in ε-caprolactone and the temperature raised to 105 °C before a catalytic amount of tin(II) 2-ethylhexanoate was added. The molar initiator/monomer ratio was determined as the product of the degree of polymerization and the number of initiating sites. The molar amount of the catalyst was ∼ 1/200. The reaction mixture was heated for 16 h, diluted with THF, and precipitated into cold methanol to give the polymers in nearly quantitative yields.
8a-d: 1H NMR (300 MHz, CDCl3, 25 °C, TMS): δ 9.17 (broad s, 8 H, β-H), 8.28 (broad s, 8 H, Ar-o,o’-H), 7.54 (broad s, 8 H, Ar-p-H), 4.06 (t, 2J (H,H) = 6 Hz, poly, CH2O), 3.65 (t, 2J (H,H) = 6 Hz, 16 H, CH2OH), 2.32 (t, 2J (H,H) = 6 Hz, poly, CH2CO), 1.701.55 (m, poly, CH2CH2), 1.45-1.35 (m, poly, CH2);
13
C NMR (125 MHz , CDCl3): δ
173.4, 173.2, 63.8, 62.2, 33.9, 32.1, 28.2, 25.3, 24.3; UV/vis (CHCl3) λmax (rel. intensity) 419 nm (1.000), 515 nm (0.046), 548 nm (0.014), 589 nm (0.013), 644 nm (0.007).
150
9a-d: 1H NMR (300 MHz, CDCl3, 25 °C, TMS): δ 9.01 (broad s, 8 H, β-H), 7.86 (broad s, 8 H, Ar-o,o’-H), 7.38 (broad s, 4 H, Ar-p-H), 4.06 (t, 2J (H,H) = 6 Hz, poly, CH2O), 3.65 (t, 2J (H,H) = 6 Hz, 32 H, CH2OH), 2.31 (t, 2J (H,H) = 6 Hz, poly, CH2CO), 1.711.59 (m, poly, CH2CH2), 1.42-1.33 (m, poly, CH2);
13
C NMR (125 MHz, CDCl3): δ
173.3, 173.1, 63.7, 62.0, 33.9, 32.0, 28.0, 25.2, 24.2; UV/vis (CHCl3) λmax (rel. intensity) 419 nm (1.000), 514 nm (0.049), 548 nm (0.017), 588 nm (0.017), 644 nm (0.008).
10a-d: 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 8.31-8.04 (m, 9 H, Ar-H), 5.89 (s, 2 H, ArCH2O), 4.06 (t, 3J (H,H) = 6 Hz, poly, CH2O), 3.95 (t, 3J (H,H) = 6 Hz, 4 H, CH2OCO), 3.65 (t, 3J (H,H) = 6 Hz, 4 H, CH2O), 2.34 (t, 3J (H,H) = 6 Hz, poly, CH2CO), 1.71-1.60 (m, poly, CH2CH2), 1.43-1.33 (m, poly, CH2), 1.24 (s, 3 H, CH3);
13
C NMR
(125 MHz, CDCl3): 173.59, 173.45, 173.40, 131.69, 131.02, 130.47, 129.48, 128.39, 128.16, 128.10, 127.83, 127.20, 126.08, 125.52, 125.44, 124.69, 124.42, 124.40, 122.72, 64.00, 63.91, 62.38, 46.37, 34.09, 33.97, 33.41, 32.19, 28.20, 28.04, 25.38, 25.18, 24.43, 17.63; UV/vis (CHCl3) λmax (rel. intensity) 267 nm (0.56), 287 nm (1.00), 315 nm (0.27), 329 nm (0.63), 345 nm (0.93).
11a-d: 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 8.30-8.05 (m, 9 H, Ar-H), 5.89 (s, 2 H, ArCH2O), 4.06 (t, 3J (H,H) = 6 Hz, poly, CH2O), 3.64 (t, 3J (H,H) = 6 Hz, 8 H, CH2O), 2.31 (t, 3J (H,H) = 6 Hz, poly, CH2CO), 1.71-1.60 (m, poly, CH2CH2), 1.44-1.33 (m, poly, CH2), 1.24 (s, 3 H, CH3), 1.04 (s, 6 H, CH3);
13
C NMR (125 MHz, CDCl3):
173.53, 173.33, 172.56, 171.82, 131.76, 130.99, 130.46, 129.43, 128.31, 128.10, 127.87, 127.85, 127.18, 126.09, 125.56, 125.46, 124.69, 124.53, 124.39, 122.51, 64.71, 64.10, 151
63.95, 62.23, 46.73, 46.15, 34.08, 33.94, 33.55, 32.19, 28.33, 28.18, 25.37, 25.21, 24.58, 24.42, 24.22, 17.43, 17.36; UV/vis (CHCl3) λmax (rel. intensity) 267 nm (0.55), 287 nm (1.00), 315 nm (0.27), 329 nm (0.62), 345 nm (0.93).
General Procedure for Metalation of Porphyrin-core Starpolymers: 1 Equiv. of polymer 8a-d or 9a-d was dissolved in CHCl3 and a small amount of methanol added. Zinc(II) acetate (5 equiv.) was added and it was stirred at room temperature. The reaction was monitored using UV/vis spectroscopy.14 After completion, the solvent was evaporated, the crude product dissolved in the minimum amount of THF, and precipitated into cold methanol. Washing with methanol and drying under vacuum gave polymers X as pinkish powders in quantitative yields.
12a-d: Both, 1H and
13
C NMR spectra remained unchanged compared to 8a-d. UV/vis
(CHCl3) λmax (rel. intensity) 425 nm (1.000), 555 nm (0.037), 593 nm (0.007).
13a-d: Both, 1H and
13
C NMR spectra remained unchanged compared to 9a-d. UV/vis
(CHCl3) λmax (rel. intensity) 425 nm (1.000), 556 nm (0.039), 593 nm (0.008).
General Procedure for End-group Modification of Starpolymers: 1 Equiv. of the hydroxyl-terminated polymer was dissolved in 60 equiv. pyridine and dry CH2Cl2. 1 Equiv. of 4-dimethylaminopyridine (DMAP) and 50 equiv. of the coumarin-3carboxylic acid chloride dissolved in CH2Cl2 were added and it was stirred at room temperature overnight. After evaporation of the solvent, the crude product was dissolved 152
in the minimum amount of THF and precipitated into cold methanol. Extensive washing with methanol and drying under vacuum gave the polymers in quantitative yield.
14a-d: This was prepared as above from polymer 9a-d and coumarin-3-carboxylic acid chloride (100 % yield). 1H NMR (300 MHz, CDCl3, 25 °C, TMS): δ 8.93 (broad s, 8 H, porph β-H), 8.53 (broad s, 16 H, cou =CH-), 7.85 (broad s, 8 H, porph Ar-o,o’-H), 7.717.63 (m, 32 H, cou Ar-H), 7.43-7.32 (m, 36 H, cou Ar-H and porph Ar-p-H), 4.36 (t, 2J (H,H) = 6 Hz, 32 H, CH2O2C-cou), 4.06 (t, 2J (H,H) = 6 Hz, poly, CH2O), 2.34 (t, 2J (H,H) = 6 Hz, poly, CH2CO), 1.71-1.60 (m, poly, CH2CH2), 1.44-1.33 (m, poly, CH2); 13
C NMR (125 MHz, CDCl3): δ 173.4, 172.9, 163.0, 155.1, 148.5, 134.2, 129.4, 124.7,
117.8, 16.6, 65.6, 64.0, 35.2, 34.0, 28.2, 25.4, 24.4; UV/vis (CHCl3) λmax (rel. intensity) 295 nm (0.878), 335 nm (0.515), 420 nm (1.000), 513 nm (0.050), 548 nm (0.017), 588 nm (0.017), 644 nm (0.010).
16: This was prepared as above from the known 1,1,1-tris(4-hydroxyphenyl)ethane-core star polymer12a,b and coumarin-3-carboxylic acid chloride (100 % yield). 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 8.54 (broad s, 6 H, cou =CH-), 7.66-7.63 (m, 12 H, cou ArH), 7.38-7.32 (m, 12 H, cou Ar-H), 7.11-6.94 (m, 12 H, Ar-H), 4.36 (t, 3J (H,H) = 6 Hz, 12 H, CH2O2C-cou), 4.06 (t, 3J (H,H) = 6 Hz, poly, CH2O), 2.34 (t, 3J (H,H) = 6 Hz, poly, CH2CO), 1.71-1.60 (m, poly, CH2CH2), 1.43-1.34 (m, poly, CH2); 13C NMR (125 MHz, CDCl3): 173.43, 173.40, 163.01, 156.50, 155.08, 148.46, 134.21, 129.43, 124.70, 118.22, 117.79, 116.66, 65.57, 64.00, 46.63, 33.99, 33.75, 28.22, 28.13, 25.40, 25.36, 24.45,
153
24.34; MW(NMR) = 14,900, PD(GPC) = 1.11; UV/vis (CHCl3) λmax 294 nm, 335 nm; λemi 418 nm.
Coumarin-labeled Porphyrin Core Dendrimer 15. Tetrakis(3,5-bis(2’,2’-dihydroxymethylpropionyloxy)phenyl)porphyrin 1b was dissolved (25 mg, 0.015 mmol) in 0.3 mL of pyridine. DMAP (1 mg, 0.007 mmol) and coumarin-3-carboxylic acid chloride (75 mg, 0.36 mmol) dissolved in 0.5 mL CH2Cl2 were added, and it was stirred at room temperature overnight. After evaporation of the solvent, the crude product was purified by flash chromatography (silica gel, 5 % MeOH in CH2Cl2) to give 15 as a brownish powder in 83 % yield. 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 8.88 (broad s, 8 H, porph βH), 8.43 (broad s, 16 H, cou =CH-), 7.91 (broad s, 8 H, porph Ar-o,o’-H), 7.83 (s, 4 H, Ar-p-H), 7.33-7.26 (m, 32 H, cou Ar-H), 6.92-6.96 (m, 32 H, cou Ar-H), 4.78 (d, 2J (H,H) = 12 Hz, 32 H, CH2O), 1.66 (s, 24 H, CH3), -3.44 (broad s, 2 H, NH); MALDITOF MS (trans-3-indoleacrylic acid matrix): m/z = 4424 (calcd for C244H158N4O80+ 4426); Anal. C: 66.40, H: 3.65, N: 1.42 (calcd C: 66.22, H: 3.60, N: 1.27); UV/vis (CHCl3) λmax (ε) 295 nm (456000), 335 nm (267000), 420 nm (519000), 513 nm (22300), 546 nm (7700), 589 nm (6500), 644 nm (3200).
Coumarin-labeled First Generation Dendron 17: Coumarin-3-carboxylic acid chloride (104 mg, 0.50 mmol) dissolved in 0.5 mL of CH2Cl2 was added to a solution of benzyl 2,2-bis(hydroxymethyl)-propionate (53 mg, 0.238 mmol), DMAP (3 mg, 0.024 mmol), and triethylamine (0.10 mL, 0.714 mmol) in 2 mL of CH2Cl2 and it was stirred at room temperature overnight. After evaporation of the solvent, the residue was taken up in 154
CH2Cl2, the organic layer extracted with 1 M HCl, brine, and dried over MgSO4. A short flash column (silica gel, ethyl acetate) afforded 127 mg of the desired product as a white powder (94 % yield). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 8.37 (s, 2 H, Coumarin C=CH), 7.65 (ddd, 3J (H,H) = 8 Hz, 7 Hz, 4J (H,H) = 2 Hz, 2 H, Coumarin Ar-H), 7.56 (dd, 3J (H,H) = 8 Hz, 4J (H,H) = 2 Hz, 2 H, Coumarin Ar-H), 7.35-7.31 (m, 4+2 H, Coumarin Ar-H + Ar-m,m’-H), 7.20 (t, 3J (H,H) = 7 Hz, 2 H, Ar-o,o’-H), 7.12 (d, 3J (H,H) = 7 Hz, 1 H, Ar-p-H), 5.22 (s, OCH2Ph), 4.68 (d, 2J (H,H) = 11 Hz, 2 H, OCH2), 4.59 (d, 2J (H,H) = 11 Hz, 2 H, OCH2), 1.49 (s, 3H, CH3); 13C NMR (500 MHz, CDCl3): δ 172.4, 162.4, 156.3, 155.1, 148.9, 135.4, 134.5, 129.7, 128.5, 128.3, 128.2, 124.7, 117.7, 117.5, 116.7, 67.0, 66.5, 46.7, 18.0; Anal. C: 67.59, H: 4.25 (calcd C: 67.60, H: 4.40); UV/vis (CHCl3) λmax (ε) 295 nm (24100), 336 nm (13100); λemi 404 nm.
Methyl Coumarin-3-carboxylate 18: Coumarin-3-carboxylic acid chloride (313 mg, 1.50 mmol) dissolved in 2 mL of CH2Cl2 was added to a solution of DMAP (12 mg, 0.15 mmol) and triethylamine (0.31 mL, 2.25 mmol) in 10 mL of MeOH, and it was stirred at room temperature overnight. After evaporation of the solvent, the residue was taken up in CH2Cl2, the organic layer extracted with 1 M HCl, brine, and dried over MgSO4. Recrystallization from EtOH gave 294 mg of the product as colorless crystals (96 % yield). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 8.58 (s, 1 H, Coumarin C=CH), 7.687.62 (m, 2 H, Coumarin Ar-H), 7.38-7.34 (m, 2 H, Coumarin Ar-H), 3.96 (s, 3 H, CO2CH3);
13
C NMR (500 MHz, CDCl3): δ 163.7, 156.7, 155.2, 149.1, 134.4, 129.5,
124.9, 117.9, 117.8, 116.8, 52.9; Anal. C: 64.60, H: 3.96 (calcd C: 64.71, H: 3.95); UV/vis (CHCl3) λmax (ε) 294 nm (14200), 335 nm (7600); λemi 400 nm. 155
References 1. (a) Newkome, G. R.; Moorefield, C. N.; Vögtle, F. Dendritic Molecules: Concepts, Synthesis, Perspectives; VCH: Weinheim, 1996. (b) Top. Curr. Chem. 1998, 197; 2000, 210; 2001, 212. (c) Bosman, A. W.; Jansen, H. M.; Meijer, E. W. Chem. Rev. 1999, 99, 1665. (d) Fréchet, J. M. J.; Hawker, C. J. In Comprehensive Polymer Science, 2nd Suppl.; Aggarwal, S. L.; Russo, S., Eds.; Pergamon Press: Oxford, 1996, p 140. (e) Fréchet, J. M. J. Science, 1994, 263, 1710. (f) Tomalia, D. A.; Naylor, A. M.; Goddard, W. A., III Angew. Chem. Int. Ed. 1990, 29, 138. 2. Functional dendrimers have been comprehensively reviewed by: (a) Chow, H.-F.; Mong, T. K.-K.; Nongrum, M. F.; Wan, C.-W. Tetrahedron 1998, 54, 8543. (b) Archut, A.; Vögtle, F. Chem. Soc. Rev. 1999, 27, 233. 3. Hecht, S.; Fréchet, J. M. J. Angew. Chem. Int. Ed. 2001, 40, 74. 4. Dendrimers as biological mimics have been reviewed in: Smith, D. K.; Diederich, F. Chem. Eur. J. 1998, 4, 1353. 5. (a) Wang, P.-W.; Liu, Y.-J.; Devadoss, C.; Bharathi, P.; Moore, J. S. Adv. Mater. 1996, 8, 237. (b) Kawa, M.; Fréchet, J. M. J. Chem. Mater. 1998, 10, 286. (c) Halim, M.; Pillow, J. N. G.; Samuel, I. D. W.; Burn, P. L.; Adv. Mater. 1999, 11, 371. (d) Freeman, A. W.; Koene, S. C.; Malenfant, P. R. L.; Thompson, M. E.; Fréchet, J. M. J. J. Am. Chem. Soc. 2000, 122, 12385. 6. (a) Dandliker, P. J.; Diederich, F.; Gross, M.; Knobler, C. B.; Louati, A.; Sanford, E. M.
Angew. Chem. Int. Ed. 1994, 33, 1739. (b) Dandliker, P. J.; Diederich, F.;
Gisselbrecht, J.-P.; Louati, A.; Gross, M. Angew. Chem. Int. Ed. 1995, 34, 2725. (c) Sadamoto, R.; Tomioka, N.; Aida, T. J. Am. Chem. Soc. 1996, 118, 3978. (d) 156
Dandliker, P. J.; Diederich, F.; Zingg, A.; Gisselbrecht, J.-P.; Gross, M.; Louati, A.; Sanford, E. M. Helv. Chim. Acta 1997, 80, 1773. (e) Pollak, K. W.; Leon, J. W.; Fréchet, J. M. J.; Maskus, M.; Abruña, H. D. Chem. Mater. 1998, 10, 30. (f) Weyermann, P.; Gisselbrecht, J.-P.; Boudon, C.; Diederich, F.; Gross, M. Angew. Chem. Int. Ed. 1999, 38, 3215. (g) Jiang, D.-L.; Aida, T. Chem. Commun. 1996, 1523. (h) Collman, J. P.; Fu, L.; Zingg, A.; Diederich, F. Chem. Commun. 1997, 193. (i) Bhyrappa, P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Am. Chem. Soc. 1996, 118, 5708. (j) Bhyrappa, P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Mol. Catal. A 1996, 113, 109. For additional work on porphyrin core dendrimers: (k) Jin, R.-H.; Aida, T.; Inoue S. J. Chem. Soc., Chem. Commun. 1993, 1260. (l) Tomoyose, Y.; Jiang, D.-L.; Jin, R.-H.; Aida, T.; Yamashita, T.; Horie, K.; Yashima, E.; Okamoto, Y. Macromolecules 1996, 29, 5236. (m) Pollak, K. W.; Sanford, E. M.; Fréchet, J. M. J. J. Mater. Chem. 1998, 8, 519. (n) Jiang, D.-L.; Aida, T. J. Am. Chem. Soc. 1998, 120, 10895. (o) Bhyrappa, P.; Vaijayanthimala, G.; Suslick, K. S. J. Am. Chem. Soc. 1999, 121, 262. (p) Kimura, M.; Shiba, T.; Muto, T.; Hanabusa, K.; Shirai, H. Macromolecules 1999, 32, 8237. (q) Vinogradov, S. A.; Lo, L.-W.; Wilson, D. F. Chem. Eur. J. 1999, 5, 1338. (r) Vinogradov, S. A.; Wilson, D. F. Chem. Eur. J. 2000, 6, 2456. (s) Matos, M. S.; Hofkens, J.; Verheijen, W.; De Schryver, F. C.; Hecht, S.; Pollak, K. W.; Fréchet, J. M. J.; Forier, B.; Dehaen, W. Macromolecules 2000, 33, 2967. 7. Accelerated growth strategies have been reported. For double-stage convergent growth approaches, see: (a) Wooley, K. L.; Hawker, C. J.; Fréchet, J. M. J. J. Am. Chem. Soc. 1991, 113, 4252. (b) Ihre, H.; Hult, A.; Fréchet, J. M. J.; Gitsov, I. 157
Macromolecules 1998, 31, 4061. For a double exponential growth approach, consult: (c) Kawaguchi, T.; Walker, K. L.; Wilkins, C. L.; Moore, J. S. J. Am. Chem. Soc. 1995, 117, 2159. The use of “hypermonomer” building blocks is described in: (d) Wooley, K. L.; Hawker, C. J.; Fréchet, J. M. J. Angew. Chem. Int. Ed. 1994, 33, 82. (e) L’abbe, G.; Forier, B.; Dehaen, W. J. Chem. Soc., Chem. Commun. 1996, 1262. Orthogonal monomers have been used by: (f) Spindler, R.; Fréchet, J. M. J. J. Chem. Soc., Perkin Trans. 1 1993, 913. (g) Zeng, F.; Zimmerman, S. C. J. Am. Chem. Soc. 1996, 118, 5326. (h) Freeman, A. W.; Fréchet, J. M. J. Org. Lett. 1999, 1, 685. 8. Recently, there have been major advances in achieving dendrimer-like properties using hyperbranched polymers. Although such materials are easily accessible via one pot procedures, the covalent encapsulation of a single entity is not currently practical using this approach. Comprehensive reviews on hyperbranched polymers include: (a) Kim, Y. H. J. Polym. Sci., Part A: Polym. Chem. 1998, 36, 1685. (b) Voit, B. I. Acta Polymerica 1995, 46, 87. (c) reference 1d. 9. For a recent review, consult: Löfgren, A.; Albertsson, A.-C.; Dubois, P.; Jerôme, R. J. Macromol. Sci., Rev. Macromol. Chem. Phys. 1995, C35, 379. 10. (a) Trollsås, M.; Hedrick, J. L.; Mecerreyes, D.; Dubois, P.; Jerôme, R.; Ihre, H.; Hult, A.
Macromolecules 1997, 30, 8508. (b) Trollsås, M.; Hedrick, J. L.;
Mecerreyes, D.; Dubois, P.; Jerôme, R.; Ihre, H.; Hult, A. Macromolecules 1998, 31, 2756. (c) Trollsås, M.; Hedrick, J. L. J. Am. Chem. Soc. 1998, 120, 4644, and references therein. 11. Ihre, H.; Hult, A.; Söderlind, E. J. Am. Chem. Soc. 1996, 118, 6388.
158
12. In all described polymer series, the index a-d indicates increasing DP. See Table 1 for further details. 13. Values given in Table 1 refer to the average DP of individual chains, as indicated in Schemes 5.5-5.9. 14. (a) Buchler, J. W. In The Porphyrins; Dolphin, D., Ed.; Academic Press: New York, 1978; Vol. I, Part A, p 390. (b) Smith, K. M. In Porphyrins and Metalloporphyrins; Smith, K. M., Ed.; Elsevier: New York, 1976; p 3 and appendix p 871. 15. Consult standard photochemistry textbooks: (a) Turro, N. J. Modern Molecular Photochemistry; University Science Books: Sausalito, 1991. (b) Gilbert, A.; Baggott, J.
Essentials of Molecular Photochemistry; CRC Press: Boca Raton, 1991. (c)
Klessinger, M.; Michl, J. Excited States and Photochemistry of Organic Molecules; VCH: Weinheim, 1995. 16. Turro, N. J.; Barton, J. K.; Tomalia, D. A. Acc. Chem. Res. 1991, 24, 332. 17. (a) Willner, L.; Jucknischeke, O.; Richter, D.; Farago, B.; Fetters, L. J.; Huang, J. S. Europhys. Lett. 1992, 19, 297. (b) Willner, L.; Jucknischeke, O.; Richter, D.; Roovers, J.; Zhou, L.-L.; Topowski, P. M.; Fetters, L. J.; Huang, J. S.; Lin, M. Y.; Hadjichristidis Macromolecules 1994, 27, 3821. 18. (a) Rudnick, J.; Gaspari, G. J. Phys. A 1986, 19, L191. (b) Aronowitz, J. A.; Nelson, D. R. J. Phys. 1986, 47, 1445. 19. Calculated by using: δ=(150f-1-140f-2)/(135-120f-1-4f-2), where f is the number of arms. For further details, consult: Wei, G.; Eichinger, B. E. J. Chem. Phys. 1990, 93, 1430. 20. Sikorski, A.; Romiszowski, P. J. Chem. Phys. 1998, 109, 6169. 159
21. (a) Förster, T. Fluoreszenz Organischer Verbindungen; Vandenhoech and Ruprech: Göttingen, 1951. (b) Van der Meer, W. B.; Coker, G., III; Chen, S.-Y. Resonance Energy Tranfer, Theory and Data; VCH: Weinheim, 1994. 22. Representative recent reviews are given in: (a) Weiss, S. Science 1999, 283, 1676. (b) Szöllösi, J.; Damjanovich, S.; Mátyus, L. Cytometry 1998, 34, 159. 23. Only
one
example
of
energy
transfer
from
a
coumarin
donor
(7-
diethylaminocoumarin-3-carboxylate) to a metalloporphyrin acceptor (palladium(II) tetraarylporphyrin) has been reported by: Kaschak, D. M.; Lean, J. T.; Waraksa, C. C.; Saupe, G. B.; Usami, H.; Mallouk, T. E. J. Am. Chem. Soc. 1999, 121, 3435. However, due to the red shifted emission of the employed coumarin, sensitization of the Q-band and not the Soret band of the metalloporphyrin most likely occured. 24. We recently found this method to be well suited for studying FRET in dendritic systems: (a) Adronov, A.; Gilat, S.; Fréchet, J. M. J.; Ohta, K.; Neuwahl, F. V. R.; Fleming, G. R. J. Am. Chem. Soc. 2000, 122, 1175. (b) Gilat, S. L.; Adronov, A.; Fréchet, J. M. J. Angew. Chem. Int. Ed. 1999, 38, 1422. (c) Adronov, A.; Malenfant, P. R. L.; Fréchet, J. M. J. Chem. Mater. 2000, 12, 1463. For a detailed discussion, see also: Devadoss, C.; Bharati, P.; Moore, J. S. J. Am. Chem. Soc. 1996, 118, 9635. Quantifying the enhanced acceptor emission was found to be associated with a much greater error arising from the almost negligible emission of the model compound having no donors chromophores. 25. (a) Seixas de Melo, J. S.; Becker, R. S.; Macanita, A. L. J. Phys. Chem. 1994, 98, 6054. (b) Schade, B.; Hagen, V.; Schmidt, R.; Herbrich, R.; Krause, E.; Eckardt, T.; Bendig, J. J. Org. Chem. 1999, 64, 9109. 160
26. A similar result has been observed in a dendritic system having a water-soluble carboxylate-functionalized periphery and a palladium porphyrin core. Different quenching constants of molecular oxygen were found with varying pH of the medium suggesting conformational changes of the dendrimer backbone. See references 6q,r for further details. 27. (a) Grest, G. S.; Kremer, K.; Milner, S. T.; Witten, T. A. Macromolecules 1989, 22, 1904. b) Li, H.; Witten, T. A. Macromolecules 1994, 27, 449. (c) Grest, G. S. Macromolecules 1994, 27, 3493. 28. (a) Light Scattering from Polymer Solutions; Huglin, M. B.; Ed.; Academic Press: New York, 1972. b) Wyatt, P. J. Anal. Chim. Acta 1993, 272, 1; and references therein. 29. Representative reviews include: (a) Johnson, C. S., Jr. Prog. Nucl. Magn. Reson. Spectrosc. 1999, 34, 203. (b) Söderman, O.; Stilbs, P. Prog. Nucl. Magn. Reson. Spectrosc. 1994, 26, 445. (c) Stilbs, P. Prog. Nucl. Magn. Reson. Spectrosc. 1987, 19, 1. (d) Price, W. S. Concepts Magn. Reson. 1998, 10, 197. (e) Price, W. S. Concepts Magn. Reson. 1997, 9, 299. 30. (a) Young, J. K. ; Baker, G. R.; Newkome, G. R.; Morris, K. F.; Johnson, C. S., Jr. Macromolecules 1994, 27, 3464. (b) Ihre, H.; Hult, A.; Söderlind, E. J. Am. Chem. Soc. 1996, 118, 6388. (c) Valentini, M.; Pregosin, P. S.; Rüegger, H. Organometallics 2000, 19, 2551. 31. Stejskal, E. O.; Tanner, J. E. J. Chem. Phys. 1965, 42, 282. 32. For details about polydisperse samples consult: (a) ref. 29. (b) Chen, A.; Wu, D.; Johnson, C. S., Jr. J. Am. Chem. Soc. 1995, 117, 7965. 161
33. (a) Kalyanasundaram, K. Photochemistry in Microheterogeneous Systems; Academic Press: London, 1987; Chapter 2, p 36. (b) Kalyanasundaram, K. In Photochemistry in Organized and Constraint Media; Ramamurthy, V., Ed.; VCH: Weinheim, 1991; p 39. 34. (a) Selinger, B. K.; Watkins, A. R. Chem. Phys. Lett. 1978, 56, 99. (b) Infelta, P. P.; Grätzel, M. J. Chem. Phys. 1979, 70, 179. (c) Atik, S. S.; Nam, M.; Singer, L. A. Chem. Phys. Lett. 1979, 67, 75. 35. James, D. A.; Arnold, D. P.; Parsons, P. G. Photochem. Photobiol. 1994, 59, 441. 36. Albery, W. J.; Bartlett, P. N.; Jones, C. C.; Milgrom, L. R. J. Chem. Research (S) 1985, 364. 37. (a) Kim, J. B.; Adler, A. D.; Longo, F. R. In The Porphyrins; Dolphin, D., Ed.; Academic Press: New York, 1978; Vol. I, Part A, p 85. (b) Rocha Gonsalves, A. M. d’A.; Varejao, J. M. T. B.; Pereira, M. M. J. Heterocyclic Chem. 1991, 28, 635. 38. McOmie, J. F.; Watts, M. W. Tetrahedron 1968, 24, 2289. 39. Wu, D.; Chen, A.; Johnson, C. S., Jr. J. Magn. Reson. A 1995, 115, 260. 40. Holz, M.; Weingärtner, H. J. Magn. Reson. 1991, 92, 115.
162
Chapter 6:
Hyperbranched Porphyrins – a Rapid Synthetic Approach to Multiporphyrin Architectures
Abstract A new class of porphyrin-containing hyperbranched polymers has been prepared via proton-transfer polymerization utilizing an A2 + B3 polycondensation approach. The described methodology provides an accelerated entry to the construction of branched multiporphyrin architectures, benefits from the simplicity of design, i.e. one pot procedure and ease of purification, and should prove to be of general use for the construction of highly branched polymers incorporating functional moieties. The prepared materials combine advantageous structural features of hyperbranched polymers with the unique chemical properties of porphyrins and their metal complexes and therefore represent attractive building blocks for the design of catalysts having multiple active sites. This chapter has been reproduced in part with permission from Chem. Commun. 2000, 313-314. Copyright 2000 Royal Society of Chemistry.
163
Introduction In recent years, significant effort has been made to prepare and study covalently linked multiporphyrin arrays1 due to their promising role in artificial photosynthesis.2 The incorporation of porphyrin units into the framework of a dendrimer3 is of special interest since the dendritic architecture allows for maximum interactions between the chromophores, a necessary condition for efficient energy and electron transfer processes. Furthermore, the incorporation of a large number of porphyrin or metalloporphyrin moieties into a large macromolecular superstructure has great promise for the design of multisite catalysts, with potentially synergistic interplay of the active sites. However, access to such multiporphyrin compounds represents a difficult synthetic challenge, thus only low generation dendritic porphyrins have been prepared to date.1,4 We describe an alternative approach to the construction of branched multiporphyrin architectures5 that takes advantage of the rapid one pot synthesis used for generating hyperbranched polymers.3e,6 This approach is based on our recent work in proton-transfer polymerization.7 The general polymerization mechanism involves initial deprotonation of a phenolic site to form the propagating phenoxide species that consequently attacks an epoxide moiety (Scheme 6.1). Subsequently, proton transfer occurs from unreacted phenolic monomer to the formed alkoxide to regenerate the propagating phenoxide species. The large acidity difference, i.e. phenoxide vs. alkoxide, creates the thermodynamic driving force for this type of polymerization. Initially, proton-transfer polymerization was carried out with an aromatic AB2 monomer to afford aromatic epoxies.7 Since then this methodology has been extended to the preparation of entirely aliphatic hyperbranched polyethers using a A2 + B3 164
polycondensation route that relies on the significantly smaller pKa difference between primary and secondary alkoxides.8 Scheme 6.1 O
O
O
Base O
O
O
O
O
O
OH O
O
Initiation
O
O
OH
Propagation
O
O
O
O
O
O
O
O
O
O
OH
O
O
O
O
O
Proton Transfer
HO
O
O
O
O O
O
O
HO
HO
O
O O
O
Propagation / Proton Transfer aromatic epoxies
In principle, it should be possible to incorporate functional moieties in such hyperbranched polymer architectures by utilizing either a functional AB2 monomer or a any combination of functional A2 + B3 monomer. Since the incorporation of both reactive 165
functionalities into a functional moiety is synthetically rather challenging in many cases, we mainly focus on the use of a functional A2 monomer as depicted in Figure 6.1. It should be noted that this approach is very general and potentially any bisphenolic functional entity could be used to prepare the respective hyperbranched polymers.
Figure 6.1. Illustration of the A2+B3 polycondensation approach for the preparation of porphyrincontaining hyperbranched polymers.
Results and Discussion Synthesis. Following our earlier work on A2 + B3 polycondensation,8 1,1,1tris(glycidyloxymethyl)ethane9 was conveniently used as the B3 epoxide-containing monomer. The initial A2 porphyrin monomer 2 was chosen due to its symmetric nature and ease of synthesis avoiding a mixed Adler-Longo type condensation (Scheme 6.2). 2,2’-Dipyrrylmethane 1,10 available via a three step synthesis, was condensed with 4hydroxybenzaldehyde under acid catalysis followed by oxidation of the formed porphyrinogen intermediate.11
166
Scheme 6.2 OH
OH
1. SCCl2 (Et2O, benzene) 0 oC 2. KOH, H2O2 (EtOH) ∆ 3. NaBH4 (EtOH, morpholine) ∆ N H
59 %
CHO
NH
1. TFA (CH2Cl2) 2. DDQ (CH2Cl2) ∆
NH
77 %
NH
N
N
NH
1 OH
2 However, polymerization attempts employing various ratios and concentrations of bisphenolic porphyrin A2 monomer 2 and the B3 monomer, i.e. 1,1,1-tris(glycidyloxymethyl)ethane, in tetrahydrofuran (THF) using potassium t-butoxide as a basic initiator did not afford any detectable amount of oligomeric material even after long reaction times (several days). We reason that this failure is caused primarily by the relatively low solubility of 2 in THF. In addition, the free base porphyrin protons are potentially interfering with the proton transfer mechanism. Hence, the porphyrin monomer 5 was synthesized, incorporating two phenolic sites in para- and ortho-position of one meso-phenyl group and a central zinc(II) ion (Scheme 6.3). It was envisaged that the ortho-hydroxy-group in monomer 5 as well as the formed polymer chain in the ortho-position would lead to increased solubility by decreasing porphyrin-porphyrin π,π-stacking interactions. A zinc complex, was chosen to prevent participation of the free base porphyrin protons in the proton transfer event but 167
still provide a neutral closed-shell system that is soluble and suitable for NMR analysis. The asymmetric zinc porphyrin A2 monomer 5 was prepared in gram quantities via a three step procedure, involving initial mixed Adler-Longo condensation12 to afford 3 followed by deprotection and metalation of free base porphyrin 4, in 10 % overall yield. Scheme 6.3
CHO
CHO
OMe
+
3
1 OMe
N H (EtCO2H, PhNO2) ∆ 11 %
N
HN
NH
N
OMe
3 OMe BBr3 (CH2Cl2) 98 %
N
Zn(OAc)2 (CHCl3, MeOH) ∆
N Zn N
N
100 %
N
HN
NH
N
OH
OH
5
4
OH
OH
Bisphenolic porphyrin A2 monomer 5 and trisepoxide B3 monomer 6 were successfully polymerized to afford hyperbranched porphyrins 7 (Scheme 6.4). The polymerizations employed equimolar ratios of the monomers as a 0.2 M solution in THF at 60 oC using a catalytic amount of base (25 mol % per phenolic group). 168
Scheme 6.4
Terminal functionality N
N Zn
N
N O
O
N
N
O N
OH
N
O OH
N
N
OH
O
OH
KOtBu
+
O
Branched unit
O
(THF) ∆
O
O
O
Linear unit
O
HO O
OH
O O
O
OH O O
O
Zn
5
6
O
OH
Zn
O
O N
N
N
O
N
Interior functionaliy
O O
N Zn
O
N
7
Initiation of the polymerization is expected to proceed via initial deprotonation of the phenol by the base catalyst, followed by ring opening of an epoxide substituent by the nucleophilic phenoxide. Regeneration of phenoxide should then occur by an efficient proton transfer from a different phenol to the formed secondary alkoxide.7 This process leads to a highly branched polyether architecture incorporating multiple porphyrin units. As schematically illustrated in Scheme 6.4, the resulting polymers 7 should possess typical features of hyperbranched polymers and consist of branched units, arising from fully reacted B3 monomer, and linear units from both monomers. Furthermore, internal hydroxyl-functionalities and residual peripheral epoxide-groups should be present in the structure and offer various opportunities for post-functionalization of the polymers.
169
Polymer Characterization. The kinetic growth profile appeared as expected for a polycondensation reaction (Figure 6.2).7,8 At high conversion, the molecular weight of the hyperbranched polyether increases rapidly via coupling of large oligomeric and polymeric fragments and therefore careful monitoring of the polymerization mixture is critical. Upon reaching MW ~ 10,000, the polymerization was stopped by removing the heating source and the resulting polymer 7 was purified by precipitation into methanol (THF:MeOH = 1:50). The polymers were obtained as dark purple powders in 50-60 % yields and are soluble in a variety of solvents such as CHCl3, THF, and DMSO. 10000
molecular weight
8000
6000
4000
2000
0 0
2
4
6
8
10
12
time / d Figure 6.2. Polymer growth as a function of reaction time (molecular weight as determined by GPC).
The hyperbranched porphyrins 7 (MW = 9900) can be obtained in fairly narrow polydispersity (PD) of less than 2 (Figure 6.3). Much higher molecular weight polymers (MW > 50000) can be obtained; however, the PD increases significantly at MW > 10000. Control over MW can easily be achieved by variation of reaction time (typically a few days). We reason that slow polymerization is due to high dilution conditions made necessary by the relatively low solubility of 5. However, higher temperatures result in 170
faster polymer growth, but an increased PD of the polymers. It should be noted that the actual MW of polymer 7 may actually be higher than measured by GPC due to the decreased hydrodynamic volume of branched polymers relative to linear polystyrene
signal intensity
standards used for MW calibration.
10
15
20
25
30
35
GPC elution time / min Figure 6.3. GPC trace of polymer 7 after precipitation into methanol (MW = 9900, PDI = 1.9).
The successful incorporation of both monomers into the polymer backbone was monitored by matrix assisted laser desorption ionization – time of flight (MALDI-TOF) mass spectrometry (Figure 6.4). Clearly, successful coupling of both monomer building blocks 5 and 6 occurs during polymerization. Unfortunately, ionization of higher molecular weight material becomes increasingly difficult by the MALDI technique. Hence, only a rough estimate of the true MW of polymers 7 can be given using analysis by both MALDI-TOF MS and GPC. UV/vis absorption spectroscopy revealed only slight changes in the absorption behavior of polymer 7 compared to monomer 5 suggesting rather weak electronic coupling of the porphyrin units, as indicated by slight shifts in the position of both Soretand Q-bands (Figure 6.5). This finding is not surprising considering the saturated alkyl
171
phenyl ether linkages since strong electronic coupling has mainly been observed for linear conjugated multiporphyrin arrays.13 1600
P2E2
P3E3
P4E4
1400
P5E5
counts
P6E6
1000
P7E7
800
P8E8
600
P9E9
400 2000
3000
4000
5000
6000
7000
8000
9000
10000
mass (m/z)
absorbance
Figure 6.4. MALDI-TOF mass spectrum of the polymerization mixture showing the incorporation of both, porphyrin (P) and epoxide (E) monomers. The peaks at lower (higher) mass correspond to the loss (addition) of one epoxide unit.
400
500
600
700
wavelength / nm Figure 6.5. UV-vis absorption spectra of monomer 5 (…..) and polymer 7 (—) in CHCl3.
However, by investigating the emission properties a 30 % decrease in fluorescence intensity of 7 compared to 5 was observed (Figure 6.6). This finding is attributed to enhanced self-quenching of the chromophores within the macromolecule, presumably via interfacial porphyrin-porphyrin π,π stacking interactions. 172
corrected fluorescence intensity 550
600
650
700
750
wavelength / nm Figure 6.6. Corrected emission spectra of monomer 5 (…..) and polymer 7 (—) in CHCl3 (λexc = 420 nm).
Conclusion For the first time, hyperbranched polymers incorporating porphyrin chromophores have been developed. The described methodology allows the rapid synthesis of multiporphyrin architectures, facilitated by the ease of purification, e.g. no chromatography, and should be of general applicability. Furthermore, structural modification of these polymers by transmetalation or derivatization of residual functional groups should provide access to a diverse set of new materials. Such polymers could serve as interesting materials for a variety of photophysical, electrochemical, and catalytic studies involving multiple active sites as well as for the construction of optoelectronic devices.14
173
Experimental General Methods: All reagents were used as received and without further purification, unless otherwise noted. 2,2’-Dipyrrylmethane 1 was synthesized in a three step sequence and 59 % overall yield according to a published procedure.10 1,1,1-Tris(glycidyloxymethyl)ethane 6 was prepared as described in the literature.9 THF was distilled under N2 over sodium/benzophenone prior to use. Column chromatography was carried out with Merck silica gel for flash columns, 230-400 mesh. NMR spectra were recorded on a Bruker AMX-300 (300 MHz) instrument with TMS or solvent carbon signal as the standards. Matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was performed on a PerSeptive Biosystems VoyagerDE spectrometer equipped with a nitrogen laser (337 nm) in delayed extraction mode and an acceleration voltage of 20 keV. Samples were prepared using a 1:20 ratio of analyte (5 mg/mL in THF) to matrix solution (trans-3-indoleacrylic acid, 10 mg/mL in THF). Elemental analyses were performed by MHW laboratories. GPC measurements were performed on a Waters 150CV plus GPC system equipped with a differential refractive index detector and a M486 UV detector (254 nm detection wavelength) using THF as the mobile phase at 45 oC and a flow rate of 1 mL/min. The samples were separated through four 5 µm PL Gel columns (Polymer Laboratories) with porosities of 100 Å, 500 Å, 1000 Å and mixed C. The columns were calibrated with 18 narrow polydispersity polystyrene samples. Electronic absorption spectra were recorded on a Cary 50 UV-Visible Spectrophotometer. Fluorescence spectra were measured of degassed solutions (1cm cells, ODmax < 0.1) using an ISA/SPEX Fluorolog 3.22 equipped with a 450 W Xe lamp, double excitation and double emission monochromators, and a digital photon-counting 174
photomultiplier. Correction for variations in lamp intensity over time and wavelength was achieved with a solid-state silicon photodiode as the reference. The spectra were further corrected for variations in photomultiplier response over wavelength and for the path difference between the sample and the reference by multiplication with emission correction curves generated on the instrument.
5,15-Di(4-hydroxyphenyl)porphyrin 2. A solution of 4-hydroxybenzaldehyde (0.42 g, 3.42 mmol) and 1 (0.50 g, 3.42 mmol) in 500 mL of CH2Cl2 was treated with 10 drops of TFA and stirred at room temperature for 20 h. Then, DDQ (3.1 g, 13.68 mmol) was added and it was refluxed for another 8 h. It was neutralized with 7 M NH3/MeOH, filtered, and the solvent evaporated. Chromatography (silica gel, 4 % MeOH in CH2Cl2) followed by recrystallization from THF/cyclohexanes afforded 650 mg of purple crystals (77 % yield). 1
H NMR (300 MHz, DMSO-d6, 25 oC, TMS): δ 10.60 (s, 2 H, meso-H), 10.02 (broad s, 2
H, OH), 9.64 (d, 3J (H,H) = 5 Hz, 4 H, β-H), 9.10 (d, 3J (H,H) = 5 Hz, 4 H, β-H), 8.08 (d, 3
J (H,H) = 8 Hz, 4 H, Ar-H), 7.28 (d, 3J (H,H) = 8 Hz, 4 H, Ar-H), -3.20 (broad s, 2 H,
NH); FAB-HRMS: m/z 494.1730 (M+, C32H22N4O2 requires 494.1743); UV/vis (CHCl3) λmax (ε) 410 nm (569000), 505 nm (26900), 541 nm (11200), 578 nm (10100), 635 nm (6300).
Preparation of Zinc 5-(2’,4’-dihydroxyphenyl)-10,15,20-triphenylporphyrin 5: 5-(2’,4’-Dimethoxyphenyl)-10,15,20-triphenylporphyrin 3. A mixture of benzaldehyde (7.26 mL, 75 mmol), 2,4-dimethoxybenzaldehyde (4.15 g, 25 mmol), and pyrrole (6.95 mL, 100 mmol) in 200 mL propionic acid/nitrobenzene (7:3) at 120 oC. After standing 175
overnight (all steps were carried out in the presence of air), the solvent was removed in vacuo, and the product isolated using chromatography (silica gel, 50 % hexanes in CH2Cl2) to give 1.79 g of 3 as a dark purple powder (11 % yield). 1H NMR (300 MHz, CHCl3, 25 oC, TMS): δ 8.82 (broad s, 8 H, β-H), 8.20-8.23 (m, 6 H, Ar-H), 7.89 (d, 3J (H,H) = 8 Hz, 1 H, 6’-Ar-H), 7.71-7.77 (m, 9 H, Ar-H), 6.86-6.90 (s and d, 3J (H,H) = 8 Hz, 1+1 H, 3’-Ar-H and 5’-Ar-H), 4.08 (s, 3 H, CH3O), 3.58 (s, 3 H, CH3O), -2.74 (broad s, 2 H, NH); FAB-HRMS: m/z 675.2756 (M+H+, C46H35N4O2 requires 675.2760); UV/vis (CHCl3) λmax (ε) 420 nm (466000), 516 nm (21000), 551 nm (9700), 591 nm (7600), 648 nm (7500). 5-(2’,4’-Dihydroxyphenyl)-10,15,20-triphenylporphyrin 4. At 0 oC, a solution of 3 (1.79 g, 2.653 mmol) in 100 mL of dry CH2Cl2 was added via an addition funnel to a solution of boron tribromide (0.55 mL, 5.836 mmol) in 25 mL of CH2Cl2. It was stirred overnight at rt, then water was added slowly followed by treatment with ammonia in methanol to adjust to basic pH. It was washed thoroughly with water, then brine, dried over MgSO4, and the solvent evaporated to afford 1.69 g of a purple powder (98 % yield). 1
H NMR (300 MHz, CHCl3, 25 oC, TMS): δ 8.86 (d, 3J (H,H) = 7 Hz, 8 H, β-H), 8.19-
8.22 (m, 6 H, Ar-H), 7.72-7.81 (m, 9+1 H, Ar-H+6’-Ar-H), 6.71-6.73 (s and d, 3J (H,H) = 8 Hz, 1+1 H, 3’-Ar-H and 5’-Ar-H), 5.02 (broad s, 2 H, OH), -2.79 (broad s, 2 H, NH); FAB-HRMS: m/z 647.2449 (M+H+, C44H31N4O2 requires 647.2447); UV/vis (CHCl3) λmax (ε) 419 nm (469000), 516 nm (20000), 551 nm (8000), 590 nm (6400), 647 nm (6500). Zinc 5-(2’,4’-dihydroxyphenyl)-10,15,20-triphenylporphyrin 5. A solution of 4 (1.69 g, 2.613 mmol) and zinc(II) acetate (1.31 g, 7.140 mmol) in 250 mL of CHCl3/MeOH 176
(4:1) was refluxed for 5 h and the progress of the reaction monitored by UV/vis spectroscopy of the Q-band region. Removal of the solvents gave a dark residue that was taken up in CH2Cl2, washed extensively with water, then brine, dried over MgSO4, and the solvent evaporated to give 1.85 of 5 as an deep pinkish/purple solid (100 % yield). 1H NMR (300 MHz, CHCl3, 25 oC, TMS): δ 8.96 (d, 3J (H,H) = 5 Hz, 8 H, β-H), 8.19-8.21 (m, 6 H, Ar-H), 7.72-7.80 (m, 9+1 H, Ar-H+6’-Ar-H), 6.72-7.76 (s and d, 3J (H,H) = 8 Hz, 1+1 H, 3’-Ar-H and 5’-Ar-H), 5.12 (broad s, 1 H, OH), 5.04 (broad s, 1 H, OH); FAB-HRMS: m/z 708.1487 (M+, C44H28N4O2Zn requires 708.1504); UV/vis (CHCl3) λmax (ε) 423 nm (517000), 551 nm (19600), 593 nm (3200).
Hyperbranched Porphyrin 7. Polymerization experiments were carried out with 0.2 M solutions of 6 (1 equiv.) and 7 (1 equiv.) in THF at 60 oC in the presence of potassium tbutoxide (0.5 equiv.). The desired polymers were obtained by precipitation of the reaction mixture into methanol (50-fold excess by volume). GPC (THF): MW = 9900; Mn = 5100; PDI = 1.9; 1H NMR (300 MHz, DMSO-d6, 25 oC): δ 8.72 (broad s, β-H), 8.13 (broad s, Ar-H), 7.72 (broad s, Ar-H+6’-Ar-H), 6.94 (broad s, 3’-Ar-H and 5’-Ar-H), 1.2-4.3 (very broad, CH2CHOH, CH2CHOH and CH2CHOH), 0.9 (broad s, CH3); UV/vis (CHCl3) λmax (ε) 425, 557, 597 nm; λem (CHCl3, λexc = 420 nm) = 606, 655 nm.
Polymerization of 2, similarly carried out as described for monomer 5, failed. No oligomeric material could be detected even after prolonged reaction times.
177
References 1. For larger branched covalent multiporphyrin arrays, see for example: (a) Officer, D. L.; Burrell, A. K.; Reid, D. C. W. Chem. Commun. 1996, 1657. (b) Mak, C. C.; Bampos, N.; Sanders, J. K. M. Angew. Chem. Int. Ed. 1998, 37, 3020. (c) Mak, C. C.; Pomeranc, D.; Montalti, M.; Prodi, L.; Sanders, J. K. M. Chem. Commun. 1999, 1083. (d) Mak, C. C., Bampos, N.; Sanders, J. K. M. Chem. Commun. 1999, 1085. (e) Nakano, A.; Osuka, A.; Yamasaki, I.; Yamasaki, T.; Nishimura, Y. Angew. Chem. Int. Ed. 1998, 37, 3023. (f) Biemans, H. A. M.; Rowan, A. E.; Verhoeven, A.; Vanoppen, P.; Latterini, L.; Foekema, J.; Schenning, A. P. H. J.; Meijer, E. W.; de Schryver, F. C.; Nolte, R. J. M. J. Am. Chem. Soc. 1998, 120, 11054. 2. Freemantle, M. Chem. & Eng. News 1998 (10/26), 37. 3. (a) Newkome, G. R.; Moorefield, C. N.; Vögtle, F. Dendritic Molecules: Concepts, Synthesis, Perspectives; VCH: Weinheim, 1996. (b) Top. Curr. Chem. 1998, 197; 2000, 210; 2001, 212. (c) Bosman, A. W.; Jansen, H. M.; Meijer, E. W. Chem. Rev. 1999, 99, 1665. (d) Chow, H.-F.; Mong, T. K.-K.; Nongrum, M. F.; Wan, C.-W. Tetrahedron 1998, 54, 8543. (e) Fréchet, J. M. J.; Hawker, C. J. In Comprehensive Polymer Science, 2nd Suppl.; Aggarwal, S. L.; Russo, S., Eds.; Pergamon Press: Oxford, 1996, p 140. (f) Fréchet, J. M. J. Science, 1994, 263, 1710. (g) Tomalia, D. A.; Naylor, A. M.; Goddard, W. A., III Angew. Chem. Int. Ed. 1990, 29, 138. 4. A first generation porphyrin dendrimer has recently been described: Norsten, T.; Branda, N. Chem. Commun. 1998, 1257.
178
5. Related linear polyethers containing porphyrin units in the main chain have been reported: (a) Scamporrino, E.; Vitalini, D. Macromolecules 1992, 25, 2625. (b) Scamporrino, E.; Vitalini, D. Macromolecules 1992, 25, 6605. 6. Kim, Y. H. J. Polym. Sci., Part A: Polym. Chem. 1998, 36, 1685. 7. Chang, H.-T.; Fréchet, J. M. J. J. Am. Chem. Soc. 1999, 121, 2313. 8. (a) Emrick, T.; Chang, H.-T.; Fréchet, J. M. J. Macromolecules 1999, 32, 6380. (b) Emrick, T.; Chang, H.-T.; Fréchet, J. M. J. J. Polym. Sci. 2000, 38, 4850. 9. Kita, T.; Yokota, M.; Masuyama, A.; Nakatsuji, Y.; Okahara, M. Synthesis 1993, 487. 10. Chong, R.; Clezy, P. S.; Liepa, A. J.; Nichol, A. W. Aust. J. Chem. 1969, 22, 229. 11. Manka, J. S.; Lawrence, D. S. Tetrahedron Lett. 1989, 30, 6989. 12. Rocha Gonsalves, A. M. d’A.; Varejao, J. M. T. B.; Pereira, M. M. J. Heterocyclic Chem. 1991, 28, 635. 13. (a) Lin, V. S.-Y.; Di Magno, S. G.; Therien, M. J. Science 1994, 264, 1105. (b) Taylor, P. N.; Huuskonen, J.; Rumbles, G.; Aplin, R.; Williams, E.; Anderson, H. L. Chem. Commun. 1998, 909. 14. A hyperbranched polymer containing carbazole units has recently been used in an electroluminescence application: Tao, X.-T.; Zhang, Y.-D.; Wada, T.; Sasabe, H.; Suzuki, H.; Watanabe, T.; Miyata, S. Adv. Mater. 1998, 10, 226.
179
Chapter 7:
Light-driven Catalysis within Dendrimers - Designing Amphiphilic Singlet Oxygen Sensitizers
Abstract The placement of a benzophenone moiety, capable of generating singlet oxygen, at the core of a dendritic unimolecular micelle, consisting of contrasting hydrophobic interior and hydrophilic exterior, leads to the first example of photocatalysis in dendrimers. The design is based on the large polarity increase associated with the singlet oxygen mediated chemical transformation, i.e. cyclopentadiene → cis-2-cyclopentene1,4-diol. Using the described concept in conjunction with light-harvesting dendrimers offers great potential for the construction of photo-driven molecular nanoreactors. This chapter has been reproduced in part with permission from J. Am. Chem. Soc. 2001, 123, 6959-6960. Copyright 2001 American Chemical Society.
180
Introduction In the attempt to mimic nature and design more complex molecular devices, dendrimers1 represent a unique class of artificial building blocks due to their structural uniformity, multivalency, and large variation of chemical composition.2 The concept of utilizing dendrimers as nanoreactors has received considerable attention over the past years since advantages of homogeneous and heterogeneous catalysis can be combined, in particular precise control over the reactive site and catalyst recyclability, respectively. Two opposite approaches have been explored, namely the attachment of catalytic sites at the periphery of a dendrimer3 as well as the placement of the active site at the core.4 The latter design traditionally suffered from the increasingly difficult mass transport in higher generation dendrimers. However, our group has recently overcome this problem by designing an amphiphilic dendritic system capable of efficiently catalyzing an elimination reaction.5 This catalytic “pump” is based on the slight change in polarity that results from the chemical transformation of an alkyl halide into an alkene. It utilizes the contrasting polar inner and non-polar outer environments of a dendrimer to preferentially accumulate substrates and stabilize transition states and intermediates in the interior, while simultaneously expelling the product to the exterior, thereby preventing inhibition. Intrigued by these promising findings and in view of our recent success with highly efficient light-harvesting dendrimers,6 we sought to expand the scope of our approach to photoreactions. We present the first results on light-driven catalysis at the core of the dendrimers, utilizing the concepts of amphiphilic design and photosensitization. Our system is based on the large polarity difference between substrate and product in the [4+2]cycloaddition 181
of singlet oxygen7 (1O2) to dienes with subsequent reduction to the allylic diol.8 By encapsulating a 1O2-sensitizing core into a globular dendrimer9 having a hydrophobic interior and hydrophilic surface dissolved in a polar solvent a nanoscale photoreactor is created. To minimize free energy the hydrophobic substrate will be concentrated near the non-polar core, where the reagent 1O2 is photogenerated, while the subsequently formed polar product will migrate to the polar solvent (Figure 7.1). The high internal substrate concentration and enhanced lifetime of 1O2 in the hydrophobic environment7 of the core constitute a favorable combination for this bimolecular reaction.
Figure 7.1. Illustration of the concept of excited state catalysis using an amphiphilic singlet oxygen sensitizer.
An o,o’,p,p’-tetraalkoxybenzophenone was chosen as the sensitizing core because of its multiple points for dendron attachment and commercial availability. In addition, both the quantum yield for generation of 1O2 and the wavelength of absorption increase upon introduction of electron donating groups into the system.10 An aliphatic polyester backbone based on 2,2-bis(hydroxymethyl) propionic acid11 was selected due to its oxidative robustness and convenient synthesis via a recently developed divergent route.12
182
The model reaction, involving formation of cis-2-cyclopentene-1,4-diol 3 from cyclopentadiene 1 and therefore an extreme polarity change (Scheme 7.1), was chosen due to (i) the intrinsically fast cycloaddition,13 that originates from the fixed s-cis configuration of the diene and minimizes competing pathways such as [2+2]cycloaddition and ene-reaction, and (ii) the very short lifetime of the initially formed endoperoxide 2.14 Furthermore, thiourea has been widely used for the chemoselective reduction of endoperoxides and does not affect ester linkages.15 Interestingly, 3 is usually synthesized via a similar route using Rose Bengal as the sensitizer16 and represents an important intermediate in some synthesis of prostaglandins.17 Scheme 7.1 Core
O O
1
hν, ISC 3
Core*
O O
O O
2
(H2N)2CS
HO
OH
3
Results and Discussion Synthesis. To avoid phenolic ester linkages, that might alter the core’s photophysical characteristics and give rise to detrimental side reactions such as Photo-Fries rearrangements, 2,2’,4,4’-tetrahydroxybenzophenone was first alkylated using 11-bromo1-undecanol, a spacer that also provides increased interior hydrophobicity, to afford 4 (Scheme 7.2).
183
Scheme 7.2 OR
RO
O O
O
O
O
O
O O
7 cat. DMAP (pyridine) rt
O
O
90%
O
O
4 R=H
RO
n=1-3
5a R=(Acet)[G-1]
6a R=(HO)2[G-1]
(pyridine) rt
H+ resin (dioxane) 80 oC
6b R=(HO)4[G-2]
OH
H n=1-3
5b R=(Acet)2[G-2]
7 cat. DMAP (pyridine) rt 89%
HO
O
H
7 cat. DMAP
79%
OH
O
(HO)2x[G-n] =
87%
35% O
O
H+ resin (dioxane) 80 oC
Br(CH2) 11OH K2CO3, 18-crown-6 (CH3CN) ∆
HO
O
O
61% OR
O
(Acet)x[G-n] =
5c R=(Acet)4[G-3] H+ resin (dioxane) 80 oC 72%
6c R=(HO)8[G-3]
A slight alteration of the existing dendrimer construction protocol,12 that utilized benzylidene protecting groups, was necessary since the benzophenone core was not compatible with the hydrogenolysis deprotection conditions. Hence, anhydride 7 was employed as acylating agent and deprotection was accomplished using acidic conditions. Repetition of the sequence afforded hydroxyl-terminated first, second, and third generation dendrimers 6a-c (Scheme 7.3). For comparison purposes model compound 8 with polar surface groups but no hydrophobic interior was prepared by Mitsunobu etherification of 2,2’,4,4’tetrahydroxybenzophenone with tri(ethylene glycol) monomethyl ether (Scheme 7.4).
184
Scheme 7.3
OH
HO
HO
OH
HO
O
O
O
OH
O OH
HO OH
HO O
O
O
O
O
HO
O
O
O
O
O
O
O
O
O O
6a
O
HO
O
O
HO
HO
OH
6b
O
OH
HO
OH OH
O
O
O
O
O
O
OH
O
O O
O
O
O
O
O
OH O
O O
O O
O
O
O
O
O
O
O O
O
O
OH
O
OH
O
O
O
O O
O
O
O O
O
O
O
OH
O
OH
O O
O HO
O
OH
HO
O
O
OH
HO
HO
OH
O OH
O
HO
HO
O
O O
HO
HO
HO
OH
O
O
O
OH
HO
O
O
O
OH
HO
HO
O
O
O
O HO
O
O
O
O
O
O
O
O
O
HO
OH
O
O
O
6c
O
HO
O
OH
O
O
OH OH
HO HO
HO
OH
OH
Scheme 7.4 HO
HO
O
O
OH
OH
52%
O
O
O
Me(OCH2CH2)3OH DIAD, PPh3 (CH2Cl2) O
185
O
O
O
O
8
O
O
O
O
O
O
O
O
Characterization. The dendrimers were characterized using a combination of chromatographic (GPC) and mass spectrometric techniques (MALDI-TOF MS) as illustrated in Figures 7.2 and 7.3. Note that the dendritic polyols 6a-c did not allow for analysis using GPC due to the strong interactions with the column, however their acetonide-protected analogs could be successfully characterized using this technique.
Figure 7.2. MALDI-TOF mass spectra of compounds 6a-c (as Ag+ adducts).
5c
25
5b
5a
8
30
elution time / min Figure 7.3. GPC traces of compounds 5a-c and model compound 8.
186
35
The UV/vis absorption spectra of 6a-c and model compound 8 are virtually identical with 2,2’,4,4’-tetramethoxybenzophenone,18 suggesting no significant alteration of the photophysical characteristics with increasing generation. When comparing third generation dendrimer 6c with model compound 8, only a slight bathochromic shift can be observed (Figure 7.4). 17500 15000
-1
ε / l*mol *cm
-1
12500 10000 7500 5000 2500 0 250
275
300
325
350
375
400
wavelength / nm
Figure 7.4. UV/vis absorption spectra of compound 6c (_____) and model compound 8 (........) in MeOH.
Catalysis. Photocatalysis experiments employing 0.1 mol% of the different generation catalysts 6a-c as well as model compound 8 were performed and the production of 3 was monitored (Figure 7.5). Although detailed kinetic analysis is complicated due to the inherent complexity of the system, relative reactivity trends can be deduced and it can clearly be seen that higher generation dendrimers lead to faster reactions and higher levels of conversion. Model compound 8, on the contrary, displayed rather low catalytic activity, while control experiments employing no catalyst showed negligible background reactions. Obviously, the size of the hydrophobic container is crucial for improved catalyst performance. We reason that the observed behavior is primarily due to the 187
increased local concentrations of substrate as well as 1O2, however solvation and solubility effects might also be operating. 50
6c
conversion / %
40
6b
30
20
6a
10
8
0
blank 0
10
20
30
40
50
60
reaction time / min Figure 7.5. Conversion (formation of 3 normalized over initial concentration of 1) as a function of reaction time for catalysts 6a-c, model compound 8, and in the absence of catalyst. Conditions: [3] : [thiourea] : [catalyst] = 1 : 0.7 : 0.001 in MeOH.19
Notably, the catalysts exhibited good photostability since less than 10 % decomposition occurred during the reaction, based on UV/vis absorbance (Figure 7.6). 1.00
absorbance change abs/abs(t=0)
6a 6b 6c 8
0.98
0.96
0.94
0.92
0.90 0
10
20
30
40
reaction time / min
50
60
Figure 7.6. UV/vis absorbance at λmax (normalized over initial λmax) as a function of reaction time for catalysts 6a-c and model compound 8 in MeOH.
188
Conclusion Excited state catalysis using dendritic nanoreactors has been accomplished by encapsulating a singlet oxygen sensitizer, such as a benzophenone derivative, at the core of an amphiphilic dendrimer. The photooxygenation of cyclopentadiene to yield cis-2cyclopentene-1,4-diol in the presence of dendritic singlet oxygen sensitizers of different generations has been studied as a model reaction since it is associated with a large polarity increase. The dendritic catalysts resemble a unimolecular micelle enforcing a high local substrate concentration around the core, where singlet oxygen is generated, as well as preferential exclusion of the polar product. In addition to more detailed studies regarding the actual mechanism, solvent effects,20 and product selectivity using acyclic dienes,21 the incorporation of more efficient photosensitizers and donor chromophores as well as the construction of larger molecular containers by accelerated strategies22 represent attractive future targets. This first example of photocatalysis in dendrimers is encouraging for the design of next generation photoreactors at the molecular scale, incorporating light-harvesting with subsequent conversion into chemical energy.
Experimental General Methods: All reagents were used as received and without further purification, unless otherwise noted. The employed ion exchange resin, Dowex WX2-100, was washed several times in refluxing dioxane prior to use. THF was distilled under N2 over sodium/benzophenone prior to use. Column chromatography was carried out with Merck silica gel for flash columns, 230-400 mesh. NMR spectra were recorded on Bruker AMX300 (300 MHz) or Bruker DRX-500 (500 MHz) instruments with TMS or solvent carbon 189
signal as the standards. Electronic absorption spectra were recorded in MeOH on a Cary 50 UV-Visible Spectrophotometer. Matrix assisted laser desorption ionization time-offlight (MALDI-TOF) mass spectrometry was performed on a PerSeptive Biosystems Voyager-DE spectrometer equipped with a nitrogen laser (337 nm) in delayed extraction mode and an acceleration voltage of 20 keV. Samples were prepared using a 1:20 ratio of analyte (5 mg/mL in THF) to matrix solution (saturated solution of 9-nitroanthracene in THF, CF3CO2Ag was added for polyols). Elemental analyses were performed by MHW laboratories. GPC measurements were performed on a Waters 150CV plus GPC system equipped with a differential refractive index detector and a M486 UV detector (254 nm detection wavelength) using THF as the mobile phase at 45 oC and a flow rate of 1 mL/min. The samples were separated through four 5 µm PL Gel columns (Polymer Laboratories) with porosities of 100 Å, 500 Å, 1000 Å and mixed C. The columns were calibrated with 18 narrow polydispersity polystyrene samples. GC was performed on a HP 6890 system equipped with an FID using a 5% crosslinked PH ME siloxane column (30 m, 0.32 mm, 0.25 µm film thickness). Catalysis Experiments: The experiments were carried out in pyrex glass vials (λ50%T = 300 nm) under a constant oxygen flow of ∼ 10 mL/min using a 300 W Hg-arc lamp (Oriel), equipped with an electronic powermeter (Molectron Max5200) to normalize for light intensity (7.6 ± 0.2 mW/cm2). Typical concentrations: [cyclopentadiene] = 75 mM, [catalysts] = 0.075 mM (1 mol%), [thiourea] = 52.5 mM in methanol, were chosen based on catalyst absorbance (abs313nm = 1). Cyclopentadiene was prepared from the dimer prior to the experiments by atmospheric cracking under nitrogen. Aliquots (100 µl) were taken at certain time intervals, the solvent evaporated in vacuo, the residue dissolved in 1 mL of 190
acetonitrile, containing 1 vol% toluene as an internal standard, and injected in the GC for quantitative analysis. The product peak areas, normalized over the peak area of the toluene standard, at the respective reaction times were quantified using linear calibration with cis-2-cyclopentene-1,4-diol (Fluka, >99%). It was corrected for the background reaction, independently measured in control experiments using identical conditions in the absence of catalyst. In addition, the absorbance of each sample was measured.
General Procedure for Preparation of Acetonides 5a-c: A procedure, similar to the one recently developed by Ihre et al.,12 has been employed. The respective polyols 4, 6a-b (1 mmol) and DMAP (0.1 mmol) were dissolved in 1 mL of dry pyridine and a solution of isopropylidene-2,2-bis(methoxy)propionic acid anhydride 7 (1.5 mmol) in 1 mL of dry CH2Cl2 was added. After stirring for 2 h at room temperature, water (1 mL) was added and it was stirred overnight. The mixture was diluted with ethyl acetate (30 mL) and the organic phase extracted with 1 M NaHSO4 (3x10 mL), 1 M Na2CO3 (3x10 mL), and brine (10 mL). After drying over MgSO4 and removal of the solvent in vacuo, the crude product was purified over a short silica flash column, eluting a gradient from pure hexanes to ethyl acetate, to give the acetonides as slightly yellow viscous oils.
5a: This was prepared as above from 2,2’,4,4’-Tetra(11’’-hydroxy-1’’-undecanoxy)benzophenone 4 and 7 (90 % yield). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 7.52 (d, 3
J (H,H) = 9 Hz, 2 H, Ar-H), 6.46 (dd, 3J (H,H) = 9 Hz, 4J (H,H) = 2 Hz, 2 H, Ar-H), 6.33
(d, 4J (H,H) = 2 Hz, 2 H, Ar-H), 4.18 (d, 3J (H,H) = 12 Hz, 8 H, CH2O), 4.14 (t, 3J (H,H) = 7 Hz, 8 H, CH2OCO), 3.97 (t, 3J (H,H) = 7 Hz, 4 H, ArOCH2), 3.75 (t, 3J (H,H) = 7 Hz, 191
4 H, ArOCH2), 3.64 (d, 3J (H,H) = 12 Hz, 8 H, CH2O), 1.78 (q, 3J (H,H) = 7 Hz, 4 H), 1.65 (q, 3J (H,H) = 7 Hz, 8 H), 0.99-1.47 (m, 96 H);
13
C NMR (125 MHz, CDCl3): δ
193.45, 174.21, 174.20, 162.81, 159.53, 131.76, 124.55, 104.69, 99.02, 98.02, 97.94, 68.03, 66.20, 66.04, 65.95, 64.87, 41.70, 29.49, 29.47, 29.45, 29.44, 29.39, 29.36, 29.19, 29.14, 28.51, 28.50, 25.98, 25.76, 25.74, 24.25, 22.93, 18.66; MALDI-TOF MS (9nitroanthracene): m/z = 1553 (calcd 1553 for C89H147O21+); GPC (Mw = 1850, PDI = 1.01).
5b: This was prepared as above from 6a and 7 (87 % yield). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 7.52 (d, 3J (H,H) = 9 Hz, 2 H, Ar-H), 6.46 (dd, 3J (H,H) = 9 Hz, 4J (H,H) = 2 Hz, 2 H, Ar-H), 6.33 (d, 4J (H,H) = 2 Hz, 2 H, Ar-H), 4.33 (s, 16 H, CH2OCO), 4.15 (d, 3J (H,H) = 12 Hz, 16 H, CH2O), 4.11 (t, 3J (H,H) = 7 Hz, 8 H, CH2OCO), 3.97 (t, 3J (H,H) = 7 Hz, 4 H, ArOCH2), 3.75 (t, 3J (H,H) = 7 Hz, 4 H, ArOCH2), 3.62 (d, 3J (H,H) = 12 Hz, 16 H, CH2O), 1.00-2.05 (m, 172 H);
13
C NMR (125 MHz, CDCl3): δ 193.51,
173.97, 171.56, 162.85, 159.59, 131.70, 124.58, 104.71, 99.05, 98.17, 68.07, 66.10, 66.05, 65.99, 64.91, 46.89, 42.02, 29.57, 29.48, 29.46, 29.45, 29.44, 29.37, 29.35, 29.21, 29.13, 28.51, 28.49, 25.96, 25.79, 25.80, 24.18, 22.90, 17.79, 17.21; MALDI-TOF MS (9-nitroanthracene): m/z = 2643 (calcd 2642 for C141H227O45+); GPC (Mw = 2800, PDI = 1.01).
5c: This was prepared as above from 6b and 7 (89 % yield). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 7.52 (d, 3J (H,H) = 9 Hz, 2 H, Ar-H), 6.46 (dd, 3J (H,H) = 9 Hz, 4J (H,H) = 2 Hz, 2 H, Ar-H), 6.33 (d, 4J (H,H) = 2 Hz, 2 H, Ar-H), 4.39 (s, 32 H, CH2OCO), 4.27 192
(s, 16 H, CH2OCO), 4.18 (d, 3J (H,H) = 12 Hz, 32 H, CH2O), 4.16 (t, 3J (H,H) = 7 Hz, 8 H, CH2OCO), 3.96 (t, 3J (H,H) = 7 Hz, 4 H, ArOCH2), 3.74 (t, 3J (H,H) = 7 Hz, 4 H, ArOCH2), 3.62 (d, 3J (H,H) = 12 Hz, 32 H, CH2O), 1.00-2.05 (m, 284 H); 13C NMR (125 MHz, CDCl3): δ 193.46, 173.99, 172.02, 171.16, 162.82, 159.61, 131.73, 124.59, 104.68, 99.03, 98.65, 98.23, 68.12, 67.21, 66.13, 66.11, 65.93, 64.94, 46.87, 46.62, 42.21, 29.53, 29.50, 29.48, 29.45, 29.44, 29.43, 29.39, 29.36, 29.26, 29.17, 28.48, 28.47, 25.97, 25.82, 25.78, 24.23, 22.92, 17.73, 17.64, 16.48; MALDI-TOF MS (9-nitroanthracene): m/z = 4820 (calcd 4821 for C245H387O93+); GPC (Mw = 4930, PDI = 1.01).
General Procedure for Preparation of Polyols 6a-c: The respective acetonides 5a-c (1 mmol) were dissolved in 10 mL of dioxane/water (10:1) and ion exchange resin (~ 1 g) was added. It was heated at 80 oC and the reaction monitored by MALDI-TOF MS. After complete removal of the acetonide protecting groups, the solution was filtered and the solvent evaporated to give the polyols as viscous slightly yellow oils.
6a: This was prepared as above from 5a (61 % yield). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 7.52 (d, 3J (H,H) = 9 Hz, 2 H, Ar-H), 6.46 (dd, 3J (H,H) = 9 Hz, 4J (H,H) = 2 Hz, 2 H, Ar-H), 6.33 (d, 4J (H,H) = 2 Hz, 2 H, Ar-H), 4.16 (dt, 3J (H,H) = 7 Hz, 4J (H,H) = 2 Hz, 8 H, CH2OCO), 3.97 (t, 3J (H,H) = 7 Hz, 4 H, ArOCH2), 3.89 (dd, 2J (H,H) = 12 Hz, 3J (H,H) = 7 Hz, 8 H, CH2OH), 3.75 (t, 3J (H,H) = 7 Hz, 4 H, ArOCH2), 3.70 (dd, 2J (H,H) = 12 Hz, 3J (H,H) = 7 Hz, 8 H, CH2OH), 3.07 (t, 3J (H,H) = 7 Hz, 4 H, OH), 3.03 (t, 3J (H,H) = 7 Hz, 4 H, OH), 1.78 (q, 3J (H,H) = 7 Hz, 4 H), 1.66 (q, 3J (H,H) = 7 Hz, 8 H), 1.00-1.45 (m, 72 H); 13C NMR (125 MHz, CDCl3): δ 193.72, 176.00, 162.91, 159.59, 193
131.84, 124.50, 104.76, 99.07, 68.23, 68.12, 68.08, 65.17, 65.15, 49.09, 49.08, 29.53, 29.50, 29.47, 29.45, 29.41, 29.36, 29.34, 29.22, 29.19, 29.15, 29.06, 28.50, 28.48, 26.00, 25.83, 17.15; MALDI-TOF MS (9-nitroanthracene, CF3CO2Ag): m/z =1501 (calcd 1499 for C77H130O21Ag+); UV/vis (MeOH) λmax (ε) 281 nm (13400), 321 nm (13200).
6b: This was prepared as above from 5b (79 % yield). 1H NMR (500 MHz, DMSO-d6, 25 o
C, TMS): δ 7.56 (d, 3J (H,H) = 9 Hz, 2 H, Ar-H), 6.49 (dd, 3J (H,H) = 9 Hz, 4J (H,H) = 2
Hz, 2 H, Ar-H), 6.38 (d, 4J (H,H) = 2 Hz, 2 H, Ar-H), 4.22 (t, 3J (H,H) = 7 Hz, 16 H, CH2OCO), 4.14 (s, 8 H, CH2OCO), 3.99 (t, 3J (H,H) = 7 Hz, 4 H, ArOCH2), 3.92 (dd, 2J (H,H) = 12 Hz, 3J (H,H) = 7 Hz, 16 H, CH2OH), 3.78 (t, 3J (H,H) = 7 Hz, 4 H, ArOCH2), 3.73 (dd, 2J (H,H) = 12 Hz, 3J (H,H) = 7 Hz, 16 H, CH2OH), 3.54 (broad t, 3J (H,H) = 7 Hz, 16 H, OH), 1.02-1.85 (m, 108 H);
13
C NMR (125 MHz, DMSO-d6): δ 193.67,
175.00, 171.85, 162.88, 159.61, 131.74, 124.47, 104.87, 99.08, 68.32, 68.22, 68.04, 65.27, 65.25, 64.83, 49.12, 46.98, 29.54, 29.51, 29.49, 29.44, 29.40, 29.38, 29.36, 29.34, 29.26, 29.20, 29.14, 29.04, 28.53, 28.49, 26.05, 25.99, 17.18, 16.88; MALDI-TOF MS (9-nitroanthracene, CF3CO2Ag): m/z = 2428 (calcd 2429 for C117H194O45Ag+); UV/vis (MeOH) λmax (ε) 282 nm (14000), 321 nm (13700).
6c: This was prepared as above from 6c (72 % yield). 1H NMR (500 MHz, DMSO-d6, 25 o
C, TMS): δ 7.56 (d, 3J (H,H) = 9 Hz, 2 H, Ar-H), 6.50 (dd, 3J (H,H) = 9 Hz, 4J (H,H) = 2
Hz, 2 H, Ar-H), 6.39 (d, 4J (H,H) = 2 Hz, 2 H, Ar-H), 4.31 (t, 3J (H,H) = 7 Hz, 32 H, CH2OCO), 4.18 (s, 16 H, CH2OCO), 4.12 (s, 8 H, CH2OCO), 4.01 (t, 3J (H,H) = 7 Hz, 4 H, ArOCH2), 3.95 (dd, 2J (H,H) = 12 Hz, 3J (H,H) = 7 Hz, 32 H, CH2OH), 3.81 (t, 3J 194
(H,H) = 7 Hz, 4 H, ArOCH2), 3.75 (dd, 2J (H,H) = 12 Hz, 3J (H,H) = 7 Hz, 32 H, CH2OH), 3.61 (broad t, 3J (H,H) = 7 Hz, 32 H, OH), 1.01-1.87 (m, 156 H);
13
C NMR
(125 MHz, DMSO-d6): δ 193.65, 174.93, 172.34, 171.76, 162.87, 159.63, 131.72, 124.51, 104.84, 99.06, 68.37, 68.28, 68.13, 68.02, 65.38, 65.29, 65.26, 64.83, 49.23, 47.02, 46.84, 29.56, 29.52, 29.50, 29.47, 29.45, 29.41, 29.39, 29.38, 29.36, 29.35, 29.28 29.21, 29.13, 29.06, 28.57, 28.46, 26.08, 25.95, 17.19, 17.01, 16.84; MALDI-TOF MS (9-nitro-anthracene, CF3CO2Ag): m/z = 4285 (calcd 4286 for C197H322O93Ag+); UV/vis (MeOH) λmax (ε) 281 nm (14800), 320 nm (14200).
Isopropylidene-2,2-bis(methoxy)propionic acid anhydride 7.
Isopropylidene-2,2-
bis(methoxy)propionic acid anhydride 7 was prepared from isopropylidene-2,2bis(methoxy)propionic acid11b similar to the known benzylidene protected derivative.12 To a solution of isopropylidene-2,2-bis(methoxy)propionic acid (13.0 g, 74.6 mmol) in 60 mL of CH2Cl2 was cooled to 0 oC and a solution of 1,3-dicyclohexylcarbodiimide (8.5 g, 41.0 mmol) in 5 mL of CH2Cl2 was slowly added. The solution was rigorously stirred overnight at room temperature and then filtered. The solvent was evaporated, the residue taken up in the minimum amount of CH2Cl2 and precipitated into 1000 mL of ice-cold hexanes. The solution was filtered again and the solvent evaporated. The remaining viscous oil was used for the acylation reaction without further purification, although still containing minor amounts of the acid-carbodiimide adduct. 1H NMR (300 MHz, CDCl3, 25 °C, TMS): δ 4.21 (d, 2J (H,H) = 12 Hz, 4 H, OCH2), 3.69 (d, 2J (H,H) = 12 Hz, 4 H, OCH2), 1.44 (s, 6 H, CH3), 1.38 (s, 6 H, CH3), 1.24 (s, 6 H, CH3).
195
2,2’,4,4’-Tetra(11’’-hydroxy-1’’-undecanoxy)benzophenone
4.
2,2’,4,4’-Tetra-
hydroxybenzophenone (246 mg, 1 mmol) and 11-bromo-1-undecanol (1.51 g, 6 mmol) were dissolved in 10 mL of acetonitrile and K2CO3 (1.11 g, 8 mmol) and 18-crown-6 (211 mg, 0.8 mmol) were added. The mixture was refluxed for 24 h, then filtered over celite and the solvent evaporated. Chromatography (silica gel, 20 % hexanes in ethyl acetate) yielded 320 mg of the product as a white powder (35 % yield). 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 7.53 (d, 3J (H,H) = 9 Hz, 2 H, Ar-H), 6.47 (dd, 3J (H,H) = 9 Hz, 4J (H,H) = 2 Hz, 2 H, Ar-H), 6.33 (d, 4J (H,H) = 2 Hz, 2 H, Ar-H), 3.97 (t, 3J (H,H) = 6 Hz, 4 H, Ar-OCH2), 3.74 (t, 3J (H,H) = 6 Hz, 4 H, Ar-OCH2), 3.64 (t, 3J (H,H) = 6 Hz, 8 H, CH2O), 0.99-1.81 (m, 76 H);
13
C NMR (125 MHz, CDCl3): δ 193.64, 162.88,
159.58, 131.79, 124.56, 104.75, 99.04, 68.08, 68.03, 62.95, 62.94, 32.76, 32.72, 29.58, 29.54, 29.51, 29.46, 29.42, 29.37, 29.35, 29.19, 29.05, 25.97, 25.80, 25.73, 25.71; HRESI-MS: 927.7307 (calcd 927.7289 for C57H99O9+).
2,2’,4,4’-Tetra(1’’,4’’,7’’,10’’-tetraoxaundecyl)benzophenone
8.
2,2’,4,4’-Tetra-
hydroxybenzophenone (246 mg, 1 mmol), triethylene glycol monomethyl ether (1.28 mL, 8 mmol), and triphenyl phosphine (2.31 g, 8.8 mmol) were dissolved in 3 mL of CH2Cl2 and diisopropyl azodicarboxylate (1.27 mL, 8.9 mmol) was added at 0 oC. The solution was stirred at room temperature for 24 h, then diluted with water (10 mL), and extracted with CH2Cl2 (3 x 25 mL). The organic phases were washed with brine and dried over MgSO4. Chromatography (silica gel, 10 % methanol in CH2Cl2) gave 436 mg of the product as a colorless viscous oil (52 % yield). 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 7.53 (d, 3J (H,H) = 9 Hz, 2 H, Ar-H), 6.51 (dd, 3J (H,H) = 9 Hz, 4J (H,H) = 2 Hz, 2 H, 196
Ar-H), 6.43 (d, 4J (H,H) = 2 Hz, 2 H, Ar-H), 4.16 (t, 3J (H,H) = 5 Hz, 4 H), 3.93 (t, 3J (H,H) = 5 Hz, 4 H), 3.87 (t, 3J (H,H) = 5 Hz, 8 H), 3.52-3.76 (m, 28 H), 3.36-3.42 (m, 20 H);
13
C NMR (125 MHz, CDCl3): δ 192.77, 162.44, 159.14, 131.96, 128.36, 124.63,
105.27, 99.70, 71.83, 71.79, 70.74, 70.65, 70.56, 70.49, 70.45, 70.35, 69.50, 69.15, 68.19, 67.46, 58.97, 58.91; HR-ESI-MS: 831.4453 (calcd 831.4378 for C41H67O17+); UV/vis (MeOH) λmax (ε) 278 nm (14400), 313 nm (13300).
2,2’,4,4’-Tetramethoxybenzophenone.18 2,2’,4,4’-Tetrahydroxybenzophenone (500 mg, 2.031 mmol), dimethyl sulfate (1.55 mL, 16.25 mmol), K2CO3 (2.81 g, 20.31 mmol), and 18-crown-6 (430 mg, 1.624 mmol) were refluxed in 5 mL of acetonitrile for 20 h. Filtration over celite, evaporation of the solvent, chromatography (silica gel, CH2Cl2), and recrystallization from ethanol gave only the trisubstituted compound (250 mg), which was dissolved in 2 mL of acetonitrile, deprotonated with KOH (50 mg, 0.89 mmol) to give the slightly pink phenoxide that was reacted with dimethyl sulfate (0.1 mL, 1 mmol). The organic layer was washed with water, brine, and dried over MgSO4. Evaporation of the solvent and subsequent recrystallization from ethanol afforded 248 mg of the product as colorless crystals (40 % yield). 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 7.50 (d, 3J (H,H) = 9 Hz, 2 H), 6.50 (dd, 3J (H,H) = 9 Hz, 4J (H,H) = 2 Hz, 2 H), 6.43 (d, 4J (H,H) = 2 Hz, 2 H), 3.86 (s, 6 H), 3.67 (s, 6 H); 13C NMR (125 MHz, CDCl3): δ 192.90, 163.34, 160.06, 132.44, 123.81, 104.31, 98.40, 55.59, 55.38; UV/vis (MeOH) λmax (ε) 278 nm (14200), 313 nm (13400).
197
References 1. (a) Newkome, G. R.; Moorefield, C. N.; Vögtle, F. Dendritic Molecules: Concepts, Synthesis, Perspectives; VCH: Weinheim, 1996. (b) Top. Curr. Chem. 1998, 197; 2000, 210; 2001, 212. (c) Bosman, A. W.; Jansen, H. M.; Meijer, E. W. Chem. Rev. 1999, 99, 1665. (d) Chow, H.-F.; Mong, T. K.-K.; Nongrum, M. F.; Wan, C.-W. Tetrahedron 1998, 54, 8543. (e) Fréchet, J. M. J.; Hawker, C. J. In Comprehensive Polymer Science, 2nd Suppl.; Aggarwal, S. L.; Russo, S., Eds.; Pergamon Press: Oxford, 1996, p 140. (f) Fréchet, J. M. J. Science, 1994, 263, 1710. (g) Tomalia, D. A.; Naylor, A. M.; Goddard, W. A., III Angew. Chem. Int. Ed. 1990, 29, 138. 2. Hecht, S.; Fréchet, J. M. J. Angew. Chem. Int. Ed. 2001, 40, 74. 3. For representative examples, see: (a) Knapen, J. W. J.; van der Made, A. W.; de Wilde, J. C.; van Leeuwen, P. W. N. M.; Wijkens, P.; van Koten, G. Nature 1994, 372, 659. (b) Seebach, D.; Marti, R. E.; Hintermann, T. Helv. Chim. Acta 1996, 79, 1710. (c) Reetz, M. T.; Lohmer, G.; Schwickardi, R. Angew. Chem. Int. Ed. 1997, 36, 1526. (d) Köllner, C.; Pugin, B.; Togni, A. J. Am. Chem. Soc. 1998, 120, 10274; (e) Kleij, A. W.; Gossage, R. A.; Klein Gebbink, R. J. M.; Brinkmann, N.; Reijerse, E. J.; Kragl, U.; Lutz, M.; Spek, A. L.; van Koten, G. J. Am. Chem. Soc. 2000, 122, 12112. (f) Breinbauer, R.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2000, 39, 3604. (g) Francavilla, C.; Drake, M. D.; Bright, F. V.; Detty, M. R. J. Am. Chem. Soc. 2001, 123, 57. 4. For representative examples, see: (a) Brunner, H. J. Organomet. Chem. 1995, 500, 39. (b) Bolm, C.; Derrien, N.; Seger, A. Synlett 1996, 387. (c) Bhyrappa, P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Am. Chem. Soc. 1996, 118, 5708. (d) Mak, C. C.; 198
Chow, H.-F.
Macromolecules 1997, 30, 1228. (e) Morao, I.; Cossío, F. P.
Tetrahedron Lett. 1997, 36, 6461. (f) Yamago, S.; Furukuwa, M.; Azuma, A.; Yoshida, J.-I. Tetrahedron Lett. 1998, 39, 3783. (g) Kimura, M.; Sugihara, Y.; Muto, T.; Hanabusa, K.; Shirai, H.; Kobayashi, N. Chem. Eur. J. 1999, 5, 349. (h) Rheiner, P. B.; Seebach, D. Chem. Eur. J. 1999, 5, 3221. (i) Oosterom, G. E.; van Haaren, R. J.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Chem. Commun. 1999, 1119. 5. Piotti, M. E.; Rivera, F.; Bond, R.; Hawker, C. J.; Fréchet, J. M. J. J. Am. Chem. Soc. 1999, 121, 9471 6. Adronov, A.; Fréchet, J. M. J. Chem. Commun. 2000, 1701. 7. (a) Singlet Oxygen; Wasserman, H., Murray, R. W., Eds.; Academic Press: New York, 1979. (b) Singlet Oxygen; Frimer, A. A., Ed.; CRC Press: Boca Raton, FL, 1985. (c) Foote, C.; Clennan, E. L. In Active Oxygen in Chemistry; Foote, C. S., Valentine, J. S., Greenberg, A., Liebman, J. F., Eds.; Chapman & Hall: London, 1995; p 105. 8. Clennan, E. L. Tetrahedron 1991, 47, 1343. 9. Oxygen quenching by palladium porphyrin core dendrimers has been utilized as a probe and should in principle involve generation of 1O2. However, no catalysis has been described. See: (a) Vinogradov, S. A.; Lo, L.-W.; Wilson, D. F. Chem. Eur. J. 1999, 5, 1338. (b) Vinogradov, S. A.; Wilson, D. F. Chem. Eur. J. 2000, 6, 2456. 10. Compare for instance the quantum yields for Φ1O2(benzophenone)
=
0.29,
1
O2 generation in benzene:
Φ1O2(4,4’-dimethoxybenzo-phenone)
=
0.34,
Φ1O2(4,4’-bis(dimethylamino)benzophenone) = 0.41. For further details, consult: 199
Gorman, A. A.; Rodgers, M. A. J. In CRC Handbook of Organic Photochemistry; Scaiano, J. C., Ed.; CRC Press: Boca Raton, FL, 1989; vol. 2, p 229. 11. (a) Ihre, H.; Hult, A.; Söderlind, E. J. Am. Chem. Soc. 1996, 118, 6388. (b) Ihre, H.; Hult, A.; Fréchet, J. M. J.; Gitsov, I. Macromolecules 1998, 31, 4061. 12. Ihre, H.; Padilla de Jesús, O. L.; Fréchet, J. M. J. J. Am. Chem. Soc. in press. 13. k = 1 x 108 M-1s-1 See: (a) Monroe, B. M. J. Am. Chem. Soc. 1981, 103, 7253. A comprehensive list of kinetic data is given in: (b) Wilkinson, F.; Brummer, J. G. J. Phys. Chem. Ref. Data 1981, 10, 809. 14. Schenck, G. O.; Dunlap, D. E. Angew. Chem. 1956, 68, 248. 15. Seçen, H.; Sütbeyaz, Y.; Balci, M. Tetrahedron Lett. 1990, 31, 1323. 16. Kaneko, C.; Sugimoto, A.; Tanaka, S. Synthesis 1974, 876. 17. For a review, consult: (a) Noyori, R.; Suzuki, M. Angew. Chem. Int. Ed. Engl. 1984, 23, 847. See also: (b) Johnson, C. R.; Penning, T. D. J. Am. Chem. Soc. 1988, 110, 4726. (c) Busato, S.; Tinembart, O.; Zhang, Z.-D.; Scheffold, R. Tetrahedron 1990, 46, 3155. (d) Dols, P. P. M. A.; Klunder, A. J. H.; Zwanenburg, B. Tetrahedron 1994, 50, 8515. 18. Van Allan, J. A. J. Org. Chem. 1958, 23, 1679. 19. In preparative experiments, a ratio of 3 : thiourea = 1.0 : 0.7 is typically used. See for instance references 16 and 17b-d. 20. Lissi, E. A.; Encinas, M. V.; Lemp, E.; Rubio, M. A. Chem. Rev. 1993, 93, 699, and references therein. 21. Compartmentation effects on product selectivity have been reported. For example in vesicles: (a) Li, H.-R.; Wu, L.-Z.; Tung, C.-H. J. Am. Chem. Soc. 2000, 122, 2446. 200
On membranes: (b) Tung, C.-H.; Guan, J.-Q. J. Am. Chem. Soc. 1998, 120, 11874. In zeolites: (c) Tung, C.-H.; Wang, H.; Ying, Y.-M. J. Am. Chem. Soc. 1998, 120, 5179. 22. (a) Hecht, S.; Ihre, H.; Fréchet, J. M. J. J. Am. Chem. Soc. 1999, 121, 9239. (b) Hecht, S.; Vladimirov, N.; Fréchet, J. M. J. J. Am. Chem. Soc. 2001, 123, 18.
201
Chapter 8:
Light-harvesting and Conversion – Towards the Next Generation Photocatalysts
Abstract The concept of light-harvesting photocatalysts as an approach toward artificial photosynthesis is introduced. It involves efficient harvest and transfer of excitation energy utilizing multiple donor chromophores to a singlet oxygen sensitizing core where it is converted into chemical energy. First efforts are described involving the design of suitable core chromophores as well as the synthesis of novel internally functionalized dendritic building blocks. These investigations promise to ultimately lead to the construction of light-driven molecular devices.
202
Introduction In an attempt to mimic natural photosynthesis, many synthetic systems have been designed, mainly focusing on the electron transfer event.1 However, an approach to combine light harvesting, utilizing multiple chromophores, with conversion to chemical energy has yet to be developed. Dendrimers2 have great potential for approaching the natural systems3 due to their large number of peripheral groups that can be used to organize many chromophores around a central location and funnel their excitation energy via efficient energy transfer to the core.4 Due to their enhanced absorption cross section, appropriate chromophore-labeled dendritic macromolecules mimic the light harvesting event occurring in natural photosynthesis. As described in the previous chapter, we recently succeeded in developing a method for excited state energy conversion using photocatalysis at the core of dendrimers.5 Our design takes advantage of the polarity difference that occurs during the course of the photooxygenation reaction and therefore contrasting environments of the dendritic photosensitizer are used to accumulate substrate near the active site and expel product to the surrounding solvent. Encouraged by these results, we sought to embed the concept of light harvesting, using donor chromophores to gather more light over the entire range of the spectrum, in combination with better photosensitizing cores in our design to create superior dendritic photocatalysts. The design of these light-harvesting photocatalysts involves a regular unimolecular micelle, providing the solvophobic driving force, in combination with a singlet oxygen sensitizing core surrounded by donor chromophores (Figure 8.1). Two types of systems can be envisioned. The first involves charged peripheral chromophores
203
that serve as donors as well as solubilizing groups, where as the second uses neutral chromophores placed at the interior and independent external polar surface groups.
Figure 8.1. Illustration of light harvesting dendritic photocatalysts. Depending on the nature of the donor chromophore, either charged peripheral (left) or neutral internal (right) dyes are used.
Since the energy transfer is expected to be more efficient due to the shorter average donor-acceptor distance, we focused on the later approach. Furthermore, the synthesis of internally chromophore-functionalized dendritic building blocks is very attractive for a variety of reasons (Figure 8.2). For instance, energy transfer cascades for broader absorption cross sections as well as improved donor-acceptor ratios possibly leading to two photon energy transfer (TPET) events can be envisioned using such dendrimers.
Figure 8.2. Potential applications for internally chromophore-labeled dendrimers include a) energy transfer cascades from layers of dyes with decreasing bandgap toward the core, b) improved energy transfer efficiencies due to high donor-acceptor ratio at close distance, and c) up-hill two photon energy transfer (TPET) from two excited donor chromophores to the core.
204
To synthesize internally functionalized dendrimers, an appropriate monomer unit has to be developed. Recently, dendritic structures containing either allyl or bromide functionalities located at interior branch points have been developed, however, all reported compounds are based on UV-absorbing aromatic units.6 Hence, an alternative purely aliphatic branched monomer was conceived based on commercially available 1,1,1-tris(hydroxymethyl)aminomethane (Scheme 8.1). Scheme 8.1 HO masking 1,3-diol functionality via acetonide formation
HO
NH2
chemoselective differentiation using nucleophilicity difference
OH
In addition to the design of donor-containing branched monomer units, the choice of the core chromophore is crucial since its intrinsic quantum yield for singlet oxygen generation will largely determine the catalytic efficiency of the dendrimer. Here, current progress towards the design and synthesis of light harvesting dendritic photocatalysts is described.
Results and Discussion Core Design. To evaluate the spectral properties of various cores, palladium tetraphenylporphyrin 1, magnesium tetraazaporphyrin 2, and phthalocyanine 3 (Scheme 8.2) were synthesized as model compounds via known synthetic routes. Macrocycles such as 2 and 3, containing aza- instead of methine-bridges, generally represent much better singlet oxygen sensitizers, however palladium porphyrins also exhibit essentially quantitative quantum yields for singlet oxygen sensitization. It is important to note that 205
porphyrin syntheses requires acidic conditions for the condensation of pyrrole with aromatic aldehydes, whereas the syntheses of tetraazaporphyrins and phthalocyanines are carried out by base-mediated cyclotetramerization of dinitriles (vide infra). Scheme 8.2
N
N Pd
N
N
N
1
N
HN N
N
N
N
N
NH
N
Mg
N
N
N
N
N
N
3
2
Macrocycle 2 was synthesized from dinitrile precursor 5, which was prepared via a two step sequence involving a Diels-Alder reaction of anthracene with dimethyl acetylene dicarboxylate followed by direct conversion of the diester 4 into the corresponding dinitrile (5) using dimethyl aluminum amide (Scheme 8.3). Scheme 8.3
MeO 2C
CO2Me
CO2Me
∆
CO2Me
CN
Me2AlNH2 ∆ (toluene)
CN
23%
74%
4
N MeMgBr
N
∆ (n-BuOH) N
N Mg N
5 2
206
N N N
The absorption characteristics of the three macrocyclic cores are shown in Figure 8.3. Palladium complex 1 exhibits typical porphyrin signatures showing the expected intense Soret band at ~420 nm, and the dominant Q band at 525. Due to its relatively weak absorbance at wavelengths above 500 nm where charged fluorescein- or rhodaminebased peripheral donor dyes emit, causing less efficient energy transfer,9 the palladium porphyrin does not represent an ideal core chromophore. However, uncharged coumarinbased dyes, such as coumarin-3-carboxylate, having broad emissions between 375 and 450 nm efficiently sensitize the porphyrin Soret band.10 Hence, porphyrin cores are suitable cores for the internal dye functionalized dendrimer design.
200000
-1
ε / l*mol *cm
-1
300000
100000
0 300
400
500
wavelength / nm
600
700
Figure 8.3. Absorption spectra of core model compounds 1 (______), 2 (............), and 3 (------) in CHCl3.
Both magnesium tetraazaporphyrin 2 and phthalocyanine 3 show absorptions in the UV range below 400 nm corresponding to their Soret bands. However, their Q bands are bathochromically shifted and much more intense as compared to the porphyrin. While cores based on structure 2 would have significant spectral overlap with donor chromophores emitting around 600 nm, phthalocyanine-based cores offer the advantage of a broader and more intense absorption cross-section in the red. In both cases, either 207
charged peripheral or uncharged internal donor chromophores would be suitable sensitizers. In addition to the evaluation of their optical properties, the desired core should be compatible with the synthesis and contain a large number of functional groups for dendron attachment. As pointed out in Chapter 3, the number and directionality of the sites for attachment of the dendritic wedges is crucial for site isolation and optimization can dramatically enhance core encapsulation in low generations. In this regard, the three model cores display very different ‘intrinsic shielding ability’ as illustrated in Figure 8.4. While phthalocyanine 3 possesses no structural features that enhance shielding, tetraphenyl porphyrin 1 contains four twisted phenyl groups facilitating encapsulation via dendritic substitution. However, tetraazaporphyrin 2 containing a triptycene-type framework represents by far the most attractive target since the core is inherently embedded in the backbone.
Figure 8.4. Spacefilling model of cores 1 (left), 2 (center), and 3 (right). Chromophore systems are shown in dark and substituents in grey.
As mentioned earlier tetraazaporphyrin and phthalocyanine syntheses require basic conditions and therefore a wide range of acid-labile hydroxyl protecting groups that are not tolerated in porphyrin synthesis, can be utilized. In particular, this allows the 208
incorporation of acetonide-protected diol functionalities that are necessary for the construction of polyester dendrimers.11 Furthermore, alcohol functionalities are superior to their phenolic counterparts due to the intrinsically more robust ester linkage, formed in dendrimer growth. Current target cores molecules are shown in Scheme 8.4. Scheme 8.4 HO
O(CH2)nOH
HO(CH2)nO
HO(CH2)nO
N
HN
NH
N
O(CH2)nOH
HO(CH2)nO
O(CH2)nOH
6a (n=3) 6b (n=11)
O
OH
OH O
HN
HO
HO
HO
O HN O
N
N
OH
OH
HO
OH O
O
O HO
HO
NH O
OH
O O
N
N
OH HO O
O
OH N O
N
O
HO
OH
HO
OH
N
O
HO
OH
O N
O
OH
N
N
NH
HO HO
O
O
N
OH
OH
O
O
OH
HO
O N
HO O(CH2)nOH
HO
OH OH
O
HO HO
HO
HO
HO
O
HO HO
HO(CH2)nO
HO
HO
HO
7
HO HO
OH HO
8
OH
Internally Labeled Dendritic Building Blocks. To construct dendrimers having chromophore units located at their interior branch points, a branched monomer containing the specific chromophore has to be designed. The monomer is based on acetonideprotected 1,1,1-tris(hydroxymethyl) aminomethane 9 that is easily accessible in large quantities (Scheme 8.5).12 A modular design involving the preparation of masked AB2type dihydroxyacids, such as 11, having a point for functional group attachment is preferred since it allow for flexible incorporation of any desired internal substituents. Furthermore, a corresponding hypermonomer,13 13, allowing for accelerated growth was prepared (Scheme 8.6). Both syntheses benefit from the ease of purification involving only a single chromatographic separation in each case and demonstrate the feasibility of chemoselective acylation, i.e. preferential amide formation. It is important to perform the carbodiimide-mediated acylations at lower temperatures (0 oC) to prevent ester formation. 209
Scheme 8.5 MeO HO
OH
HO
.
OMe
OH O
PTSA
NH2 HCl
OH
O O
9
75-90%
O
NH2 + HO
O
(DMF) rt
DMAP
DIC (CH2Cl2) 92%
O O
OH
O
O
O
(MeCN) ∆
10
95%
O
N H
O O
11
Scheme 8.6 OH O Br HO CO2H HO
O
O DMAP
(MeCN) ∆
(MeCN) ∆
90%
67%
O
HO O
NH O
O O
K2CO3
OH
O
O
DIC
O
O
(CH2Cl2)
O
40%
O HO
9
NH2
O
O O O
O
O
O
O O
O NH
12
O OH
13
Although functionalization with coumarin-3-carboxylate to yield 14 as well as unmasking of the diol functionality to yield 15 were successful, the corresponding dendritic structures could unfortunately not be prepared due to the inability to remove the carboxylic acid protecting group using Pd-catalyzed deallylation conditions to give 16 (Scheme 8.7). Presumably, the amide linkage coordinates to the catalyst and inhibits the reaction. To avoid carboxylic acid protection, the initial strategy had to be refined by reversal of the chromophore and acid linker incorporation steps.
210
Scheme 8.7 HO
O
HO
O
NH O
H2SO4 (THF/H2O) 67 %
O Cl O O
O
O
11
O O
O
15
O
O
O
NH O
(pyridine/CH2Cl2)
O
OH
O
DMAP
O
NH
O
O
O
O
71%
O
O
14
O morpholine cat. Pd (THF)
O
O
OH
NH O
O
O O
O
16
The modified synthesis shown in Scheme 8.8 involves initial coupling of coumarin-3-carboxylic acid to 9 using the higher nucleophilicity of the amine to preferentially form amide 17, which was converted to acid 18 by introduction of a succinic acid linker. Scheme 8.8 O OH
OH O
O
EDC NH2
O
9
(CH2Cl2) 0 oC 60%
O
O
O O HO
O N H O
O
17
O
O
O
DMAP
O
(MeCN) ∆
O
49%
OH
O O
NH O O
O
18
Functional monomer 18, which can be conveniently prepared on a multigram scale, was used in first coupling reactions to yield the first generation porphyrin core dendrimer 19 (Scheme 8.9). Several coupling agents were employed and the best results 211
were obtained using a polystyrene-supported carbodiimide that greatly facilitated the purification process by retaining the urea byproduct on the solid support. Scheme 8.9 O
O O
O
O
O O
O O O
O
O
HO
OH
O
O O
18
HO
N
HN
NH
N
OH
O
O
O
O
O
O
O
NH
O
O O
PS-carbodiimide cat. DPTS/DMAP
O
O
O
O
(pyridine) rt OH
O
O
O NH
O
O
O
O
O
O
O
O
O
NH
O
HO
OH
NH
NH
O
65%
O
N
HN
NH
N
O
O
O
O
O
O
O HO
OH
TDHPP
O NH
O
O
O
O
O
O
O
O
O
NH
O O
O
O
O
O
O
NH
NH
O
O O
O O O
O
O O
O
19
O O
First insight into the spectral properties of compound 19 was gained by UV/vis spectroscopy that showed absorption maxima corresponding to the coumarin as well as the porphyrin chromophores (Figure 8.5). In fluorescence measurements, selective excitation of the coumarin donor chromophores led emission arising exclusively from the porphyrin acceptor core (Figure 8.5). This demonstrates quantitative energy transfer from the coumarin to the porphyrin, as expected considering the rather large Förster radius of 8.6 nm of this particular donor-acceptor pair.10 These results show the main advantage of a design incorporating internal donor chromophores, i.e. high energy transfer efficiencies and synthetic accessibility, and are encouraging for future studies.
212
emission
absorbance 300
400
500
wavelength / nm
600
700
Figure 8.5. Absorption (_____) and emission spectra (------, λexc = 350 nm) of compound 19 in CHCl3.
Donor Chromophores. In order to access light-harvesting systems that utilize the entire solar spectrum, donor chromophores absorbing above 450 nm and emitting above 500 nm have to be incorporated into the backbone. Such chromophores usually consist of rather extended π-conjugated systems and small molecules, suitable as substituents of a branched monomer, are hardly accessible. An interesting candidate is 7-(N-ethylamino)4-trifluoromethyl-coumarin (Coumarin 500) due to its relatively small size and the availability of a chemical handle. Although reactivity of the secondary aromatic amine was rather low, the dye could be alkylated using t-butyl bromoacetate (Scheme 8.10). However, subsequent deprotection of 20 did not afford the desired acid-functionalized monomer, but yielded the decarboxylation product 21 instead, presumably due to the extremely electron-withdrawing coumarin substituent. Therefore, other systems based on benzopyranones14 have been investigated as suitable donor chromophores. These extended coumarin-type dyes were conveniently synthesized by reacting 2,7-dihydroxynaphthalene with ethyl 4,4,4-trifluoroacetoacetate 213
(Scheme 8.11).15 Interestingly, only one regioisomer was isolated after recrystallization. The carboxylic acid functionality was introduced using the t-butyl bromoacetate alkylation/deprotection method described above. In this case, the free acid 24 could be isolated and is currently incorporated into monomer building blocks. Scheme 8.10 O CF3
CF3
Br
O
CF3 TFA
K2CO3 N H
O
N
(DMF) 110 oC
O
O
O
60%
N
(CH2Cl2) rt
O
O
20
O
O
21
Scheme 8.11
O
HO
O
O
O OH
O
OH
O OEt
CF3
O CF3
K2CO3
o
80 % H2SO4, 0 C OH
Br
O
O CF3
TFA
(DMF) 110 oC O
48%
O
(CH2Cl2) rt O
97%
22
CF3
23
O
O
71%
O
24
Conclusion and Outlook First efforts toward the design and synthesis of light-harvesting catalysts have been described and two different design strategies have been considered. Tetraazaporphyrin and phthalocyanine cores have been identified as attractive targets due to their large absorption cross-section in the red region of the spectrum, their intrinsically high quantum yields for singlet oxygen generation, and their synthesis that tolerates acidlabile protecting groups. Furthermore, a dye-labeled monomer has been developed to introduce donor chromophores at the interior branch points of the dendrimer structure. 214
The first model compound carrying internal donor chromophores around a porphyrin acceptor core has been synthesized and exhibits quantitative energy transfer. In the near future, such building blocks will be used to synthesize light-harvesting nanoreactors utilizing dendritic or star-type polymer backbones (Figure 8.6).
Figure 8.6. Designing light-harvesting photocatalysts from internal building blocks using either dendritic architectures (left) or a star morphology (right).
Experimental General Methods: All reagents were used as received and without further purification, unless
otherwise
monoallyl
noted.
succinate
methylpropionate17
5-Amino-5-hydroxymethyl-2,2-dimethyl-1,3-dioxane
10,16
were
dihydroxyphenyl)porphyrin18
as
prepared
well
as
allyl
according
(TDHPP)
was
to
9,12
3-hydroxy-2-hydroxymethyl-2the
prepared
literature. from
pyrrole
Tetrakis(3,5and
3,5-
dimethoxybenzaldehyde using Adler-Longo condensation conditions19 followed by boron tribromide deprotection.20 Phthalocyanine was prepared from phthalonitrile using a 215
reported procedure.21 Palladium tetraphenylporphyrin was prepared via standard metalation conditions using the respective free-base porphyrin and palladium(II) acetate.22 THF was distilled under N2 over sodium/benzophenone prior to use. Column chromatography was carried out with Merck silica gel for flash columns, 230-400 mesh. NMR spectra were recorded on Bruker AMX-300 (300 MHz) and Bruker DRX-500 (500 MHz) instruments with TMS or solvent carbon signal as the standards. Matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was performed on a PerSeptive Biosystems Voyager-DE spectrometer equipped with a nitrogen laser (337 nm) in delayed extraction mode and an acceleration voltage of 20 keV. Samples were prepared using a 1:20 ratio of analyte (5 mg/mL in THF) to matrix solution α-cyano-4-hydroxycinnamic acid, saturated in THF). Elemental analyses were performed by MHW laboratories. Electronic absorption spectra were recorded on a Cary 50 UV-Visible Spectrophotometer. Fluorescence spectra were measured of degassed solutions (1cm cells, ODmax < 0.1) using an ISA/SPEX Fluorolog 3.22 equipped with a 450 W Xe lamp, double excitation and double emission monochromators, and a digital photon-counting photomultiplier. The sample 19 and model compound methyl coumarin3-carboxylate were excited at 350 nm, slit widths were set to 2 nm bandpass for excitation and 5 nm bandpass for emission. Correction for variations in lamp intensity over time and wavelength was achieved with a solid-state silicon photodiode as the reference. The spectra were further corrected for variations in photomultiplier response over wavelength and for the path difference between the sample and the reference by multiplication with emission correction curves generated on the instrument.
216
Preparation of Acetylenedicarboxamide.23 Dimethyl acetylenedicarboxylate (5 mL, 40.7 mmol) was added to an aqueous solution of NH3 (30 mL, 5 M) at –10 oC and it was stirred vigorously. After 10 min, the formed precipitate was filtered, washed with ice-cold water, and dried in vacuo to afford 2.85 g of a white powder (63 % yield). NMR data of acetylenedicarboxamide have not been reported previously. 1H NMR (500 MHz, DMSOd6, 25 oC, TMS): δ 8.34 (broad s, 2 H, NH), 7.86 (broad s, 2 H, NH);
13
C NMR (125
MHz, DMSO-d6): δ 152.6, 76.9.
Preparation of Dimethyl 9,10-dihydro-9,10-ethenoanthracene-11,12-dicarboxylate 4.24 A mixture of anthracene (2.67 g, 15 mmol) and dimethyl acetylenedicarboxylate (5.5 mL, 45 mmol) was heated at 110 oC for 12 h. The anthracene dissolved during the course of the reaction. On cooling, the product crystallized. Washing with methanol followed by recrystallization from methanol afforded 3.55 g of 4 as colorless crystals (74 % yield).
Preparation of 11,12-Dicyano-9,10-dihydro-9,10-ethenoanthracene 5.25 A solution of 4 (3.55 g, 11.1 mmol) in 45 mL of dry toluene was cooled to 0 oC and freshly prepared dimethyl aluminum amide26 (37 mL, ∼ 1.2 M in toluene/CH2Cl2=2:1) was added via a syringe. The mixture was refluxed and after 15-20 min, the color of the solution turned dark red, accompanied by vigorous gas evolution. The reaction was monitored by 1HNMR and after completion (12 h), the solution was cooled to 0 oC. Water (20 mL) was added, again leading to vigorous gas evolution, and it was stirred for 1 h at room temperature. After addition of more water (80 mL), it was extracted with CH2Cl2 (4x100 mL), the collected organic layers washed with brine, dried over MgSO4, and the solvent 217
evaporated. Column chromatography (silica gel, 50% CH2Cl2 in hexanes) gave 640 mg of 5 as white powder (23 % yield). Although 5 is described in the literature,25 some characterizational data have not been reported. 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 7.42 (dd, 3J (H,H) = 6 Hz, 3 Hz, 4 H, Ar-H), 7.12 (dd, 3J (H,H) = 6 Hz, 3 Hz, 4 H, ArH), 5.42 (s, 2 H, CH); 13C NMR (125 MHz, CDCl3): δ 141.0, 137.0, 126.6, 124.4, 113.7, 54.0; FTIR (KBr, cm-1) ν 3072, 3019, 2221, 1474, 1462, 1185, 1144.
Preparation of Magnesium 2,3;7,8;12,13;17,18-tetrakis(9,10-dihydroanthracene9,10-diyl)porphyrazine 2.27 2 was prepared from 5 according to literature procedures.27 The following characterizational data have not been reported. 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 7.82 (dd, 3J (H,H) = 6 Hz, 3 Hz, 16 H, Ar-H), 7.12 (s, 8 H, CH), 6.99 (dd, 3J (H,H) = 6 Hz, 3 Hz, 16 H, Ar-H); λem(CHCl3) = 609 nm (at λexc = 368 nm).
Preparation of Tetrakis[3,5-di(3-hydroxypropyloxy)]porphyrin 6a: TDHPP (50 mg, 0.067 mmol), 3-bromopropanol (0.073 mL, 0.808 mmol), 18 crown-6 (21 mg, 0.081 mmol) were dissolved in 1 mL of DMF, potassium carbonate (130 mg, 0.942 mmol) was added, and it was heated at 120 oC for 24 h. Dilution with ethyl acetate, filtration, followed by extraction of the filtrate with water and brine, drying over MgSO4, evaporation of the solvent and purification by a short column (silica gel, 10 % MeOH in CH2Cl2) gave 52 mg of the desired product (64 % yield). 1H NMR (500 MHz, CDCl3, 25 o
C, TMS): δ 8.95 (broad s, 8 H, porph β-H), 7.37 (d, 4J (H,H) = 2 Hz, 8 H, porph Ar-o,o’-
H), 6.99 (d, 4J (H,H) = 2 Hz, 4 H, Ar-p-H), 4.59 (broad s, 8 H, OH), 4.25 (t, 3J (H,H) = 6 Hz, 16 H, CH2OH), 3.62 (t, 3J (H,H) = 6 Hz, 16 H, CH2OAr), 1.96 (dt, 3J (H,H) = 6 Hz, 6 218
Hz, 16 H, CH2CH2CH2), -2.97 (broad s, 2 H, NH); MALDI-TOF MS (α-cyano-4hydroxycinnamic acid matrix): m/z = 1208.5 (calcd for C68H78N4O16+ 1208.4).
Preparation of Tetrakis[3,5-di(11-hydroxyundecanoxy)phenyl]porphyrin 6b. A mixture of TDHPP (100 mg, 0.135 mmol), 11-bromo-1-undecanol (406 mg, 1.616 mmol), K2CO3 (261 mg, 1.885 mmol), and 18-crown-6 (50 mg, 0.188 mmol) in 5 mL of acetonitrile was refluxed until full conversion as indicated by MALDI-TOF MS (30 h). It was filtered, the solvent evaporated, and the residue chromatographed (silica gel, ethyl acetate to elute excess alkylating agent, then 5 % MeOH in ethyl acetate to elute product) to afford 180 mg of a dark viscous oil (63 % yield). 1H NMR (300 MHz, CDCl3, 25 °C, TMS): δ 8.94 (broad s, 8 H, β-H), 7.36 (d, 4J (H,H) = 2 Hz, 8 H, Ar-H), 7.55 (t, 4J (H,H) = 2 Hz, 4 H, Ar-H), 4.11 (t, 3J (H,H) = 7 Hz, 16 H, CH2OH), 3.56 (t, 3J (H,H) = 7 Hz, 16 H, CH2O), 1.86 (t, 3J (H,H) = 7 Hz, 16 H, OH), 1.58-1.24 (m, 144 H, -CH2-), -2.86 (broad s, 2 H, NH); MALDI-TOF MS (α-cyano-4-hydroxycinnamic acid matrix): m/z = 2106 (calcd for C132H207N4O16+ 2106); Anal. C: 75.36, H: 9.75, N: 2.48 (calcd C: 75.31, H: 9.86, N: 2.66); UV/vis (MeOH) λmax (ε) 415 nm (510000), 512 nm (21800), 546 nm (7700), 587 nm (6700), 645 nm (3000).
Preparation of (Acetonide){OH}[G-1]CO2allyl 11. 1,3-Diisopropylcarbodiimide (2.14 mL, 13.65 mmol) were added to a solution of 5-amino-5-hydroxymethyl-2,2-dimethyl1,3-dioxane 9 (2.00 g, 12.41 mmol) and monoallyl succinate 10 (1.98 g, 12.53 mmol) in 8 mL of CH2Cl2 at 0 oC. After stirring for 8 h, the mixture was filtered, washed with 5 mL ice-cold CH2Cl2, and the solvent evaporated. Chromatography (silica gel, 20 % hexanes 219
in ethyl acetate) gave 3.48 g of 11 as a colorless viscous oil (92 % yield). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 6.40 (broad s, 1 H, NH), 5.92-5.88 (m, 1 H, =CH-), 5.32 (dm, 3J (H,H) = 18 Hz, 1 H, trans-C=CH2), 5.24 (dm, 3J (H,H) = 10 Hz, 1 H, cisC=CH2), 4.68 (t, 3J (H,H) = 7 Hz, 1 H, OH); 4.61 (dt, 3J (H,H) = 6 Hz, 1 Hz, 2 H, CO2CH2-C=), 3.88 (d, 2J (H,H) = 12 Hz, 2 H, -CH-OC), 3.82 (d, 2J (H,H) = 12 Hz, 2 H, -CHOC), 3.70 (d, 3J (H,H) = 7 Hz, 2 H, CH2-OH), 2.72 (t, 3J (H,H) = 7 Hz, 2 H, CH2-CH2), 2.59 (t, 3J (H,H) = 7 Hz, 2 H, CH2-CH2), 1.45 (s, 6 H, CH3);
13
C NMR (125 MHz,
CDCl3): δ 172.7, 172.4, 131.9, 118.4, 98.8, 65.5, 64.2, 63.9, 55.1, 31.4, 29.4, 27.4, 19.6; Anal. C: 55.66, H: 7.50, N: 4.69 (calcd C: 55.80, H: 7.69, N: 4.65).
Preparation of (CO2H)2[G-1]CO2allyl 12. 4-Dimethylaminopyridine (DMAP, 0.005 g, 0.40 mmol) was added to a solution of allyl 3-hydroxy-2-hydroxymethyl-2methylpropionate (0.70 g, 4.02 mmol) and succinic anhydride (0.84 g, 8.44 mmol) in 7 mL of acetonitrile and it was refluxed for 12 h. Unreacted succinic anhydride was hydrolyzed by addition of water (1mL) and heating at 50 oC overnight. The reaction mixture was taken up in ethyl acetate, extracted with sat. NH4Cl and brine, dried over MgSO4, and the solvent evaporated to give 1.00 g of 12 as a colorless viscous oil (67 % yield). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 9.93 (very broad s, 2 H, CO2H), 5.925.87 (m, 1 H, =CH-), 5.32 (dm, 3J (H,H) = 18 Hz, 1 H, trans-C=CH2), 5.25 (dm, 3J (H,H) = 10 Hz, 1 H, cis-C=CH2), 4.63 (dt, 3J (H,H) = 6 Hz, 1 Hz, 2 H, CO2-CH2-C=), 4.31 (d, 2
J (H,H) = 11 Hz, 2 H, -CH-OC), 4.23 (d, 2J (H,H) = 11 Hz, 2 H, -CH-OC), 2.68-2.65 (m,
2 H, CH2-CH2), 2.66-2.61 (m, 2 H, CH2-CH2), 1.26 (s, 3 H, CH3); 13C NMR (125 MHz,
220
CDCl3): δ 177.9, 172.4, 171.2, 131.6, 118.6, 65.7, 65.3, 46.2, 28.8, 28.7, 17.9; Anal. C: 51.19, H: 5.86 (calcd C: 51.34, H: 5.92).
Preparation of (Acetonide)2{OH}2[G-2]CO2allyl 13. 1,3-Diisopropylcarbodiimide (0.76 mL, 4.9 mmol) were added to a solution of 5-amino-5-hydroxymethyl-2,2-dimethyl1,3-dioxane 9 (0.77 g, 4.76 mmol) and 12 (0.87 g, 2.32 mmol) in 3 mL of CH2Cl2. After stirring overnight, the mixture was filtered and the solvent evaporated. Chromatography (silica gel, 5 % methanol in CH2Cl2) afforded 0.62 g of 13 as a colorless oil (40 % yield). As the major byproduct, 0.58 g of the mixed amide/ester adduct was isolated. 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 6.42 (broad s, 2 H, NH), 5.94-5.86 (m, 1 H, =CH-), 5.32 (dm, 3J (H,H) = 17 Hz, 1 H, trans-C=CH2), 5.26 (dm, 3J (H,H) = 10 Hz, 1 H, cisC=CH2), 4.67 (broad s, 2 H, OH), 4.63 (dt, 3J (H,H) = 6 Hz, 1 Hz, 2 H, CO2-CH2-C=), 4.30 (d, 2J (H,H) = 11 Hz, 2 H, -CH-OC), 4.24 (d, 2J (H,H) = 11 Hz, 2 H, -CH-OC), 3.88 (d, 2J (H,H) = 12 Hz, 4 H, -CH-OC), 3.82 (d, 2J (H,H) = 12 Hz, 4 H, -CH-OC), 3.71 (s, 4H, CH2-O2C), 2.67 (t, 3J (H,H) = 7 Hz, 2 H, CH2-CH2), 2.55 (t, 3J (H,H) = 7 Hz, 2 H, CH2-CH2), 1.45 (s, 12 H, CH3), 1.27 (s, 3 H, CH3);
13
C NMR (125 MHz, CDCl3): δ
172.6, 172.4, 172.3, 131.6, 118.6, 98.9, 65.7, 65.2, 64.1, 63.8, 55.2, 46.3, 31.2, 29.3, 27.1, 19.9, 17.9; Anal. C: 54.79, H: 7.14, N: 4.22 (calcd C: 54.54, H: 7.32, N: 4.24).
Preparation of (Acetonide){Cou}[G-1]CO2allyl 14. Coumarin-3-carboxylic acid (1.89 g, 9.96 mmol) was suspended in 20 mL CH2Cl2 and oxalyl chloride (1.09 mL, 12.44 mmol) added. After addition of a catalytic amount of DMF (2 drops) the reaction mixture started to reflux and was held at reflux temperature for 2 h. Evaporation of the solvent 221
and drying in vacuum afforded the coumarin-3-carboxylic acid chloride, which was dissolved in 20 ml CH2Cl2 and slowly added to a solution of 11 (2.5 g, 8.3 mmol) in 7 mL of pyridine at 0 oC. After stirring for 12 h, the mixture was filtered, the filtrate diluted with 100 mL of ethyl acetate, the organic layer washed with 1 M NaHSO4 (2x), sat. NaHCO3, brine, dried over MgSO4, and the solvent evaporated. Chromatography (silica gel, 30 % hexanes in ethyl acetate) afforded 2.8 g of 14 as a white foam (71 % yield). 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 8.60 (s, 1 H, cou =CH-), 7.71-7.65 (m, 2 H, cou Ar-H), 7.39-7.34 (m, 2 H, cou Ar-H), 6.27 (broad s, 1 H, NH), 5.95-5.82 (m, 1 H, =CH-), 5.28 (dm, 3J (H,H) = 18 Hz, 1 H, trans-C=CH2), 5.20 (dm, 3J (H,H) = 11 Hz, 1 H, cisC=CH2), 4.72 (s, 2 H, CH2-CO2-cou), 4.56 (dt, 3J (H,H) = 6 Hz, 1 Hz, 2 H, CO2-CH2C=), 4.33 (d, 2J (H,H) = 12 Hz, 2 H, -CH-OC), 3.98 (d, 2J (H,H) = 12 Hz, 2 H, -CH-OC), 2.68 (t, 3J (H,H) = 6 Hz, 2 H, CH2-CH2), 2.55 (t, 3J (H,H) = 6 Hz, 2 H, CH2-CH2), 1.52 (s, 3 H, CH3), 1.46 (s, 3 H, CH3);
13
C NMR (125 MHz, CDCl3): δ 172.4, 172.2, 163.3,
157.0, 155.2, 149.5, 134.6, 132.0, 129.7, 125.0, 118.2, 118.0, 117.8, 116.8, 98.8, 65.3, 65.2, 62.6, 52.8, 31.2, 29.2, 24.5, 22.6; Anal. C: 60.85, H: 5.61, N: 2.97 (calcd C: 60.88, H: 5.75, N: 2.96).
Preparation of (OH)2{Cou}[G-1]CO2allyl 15. 14 (0.11 g, 0.21 mmol) was dissolved in 2 mL of THF, 0.4 mL of 2 M H2SO4 added, and it was stirred at room temperature for 6 h. After evaporation of the solvent and chromatography (20 % hexanes in CH2Cl2) 0.12 g of 14 were isolated as a white powder (67 % yield). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 8.72 (s, 1 H, cou =CH-), 7.73-7.68 (m, 2 H, cou Ar-H), 7.41-7.38 (m, 2 H, cou Ar-H), 7.12 (broad s, 1 H, NH), 5.90-5.84 (m, 1 H, =CH-), 5.28 (dm, 3J (H,H) = 17 Hz, 1 222
H, trans-C=CH2), 5.20 (dm, 3J (H,H) = 10 Hz, 1 H, cis-C=CH2), 4.57 (s, 2 H, CH2-CO2cou), 4.55 (dt, 3J (H,H) = 6 Hz, 1 Hz, 2 H, CO2-CH2-C=), 3.78 (d, 2J (H,H) = 12 Hz, 2 H, -CH-OC), 3.58 (d, 2J (H,H) = 12 Hz, 2 H, -CH-OC), 2.70 (t, 3J (H,H) = 6 Hz, 2 H, CH2CH2), 2.61 (t, 3J (H,H) = 6 Hz, 2 H, CH2-CH2);
13
C NMR (125 MHz, CDCl3): δ 173.2,
172.2, 163.2, 157.9, 155.0, 150.9, 135.0, 131.9, 129.8, 125.3, 118.2, 117.8, 117.2, 116.7, 67.3, 65.3, 64.0, 60.0, 31.1, 29.3; Anal. C: 58.26, H: 5.26, N: 3.38 (calcd C: 58.20, H: 5.35, N: 3.23).
Preparation
of
(Acetonide){Cou}[G-1]OH
17.
1-[3-(Dimethylamino)propyl]-3-
ethylcarbodiimide (13.1 g, 68.2 mmol) was added to a solution of 5-amino-5hydroxymethyl-2,2-dimethyl-1,3-dioxane 9 (10.0 g, 62.0 mmol) and coumarin-3carboxylic acid (11.8 g, 62.0 mmol) in 300 mL of CH2Cl2 at 0 °C. The mixture was allowed to warm to room temperature while stirring overnight. The reaction mixture was extracted with 1M NaHSO4 and brine, dried over MgSO4, and the solvent evaporated. Chromatography (silica gel, 3% methanol in CH2Cl2) afforded 12.50 g of 17 as a white solid (60 % yield). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 9.82 (broad s, 1 H, NH), 8.91 (s, 1 H, HC=C), 7.70 (m, 2 H, Ar-H), 7.42 (m, 2 H, Ar-H), 5.10 (t, 3J(H,H) = 7 Hz, 1 H, OH), 3.98 (d, 2J(H,H) = 11 Hz, CH2O), 3.94 (d, 2J(H,H) = 11 Hz, CH2O), 3.81 (d, 3
J(H,H) = 7 Hz, 2 H, CH2OH), 1.52 (s, 3 H, CH3), 1.49 (s, 3 H, CH3);
13
C NMR (125
MHz, CDCl3): δ 162.3, 161.3, 154.6, 148.7, 134.4, 129.9, 125.4, 118.5, 118.4, 116.7, 99.0, 64.4, 55.9, 27.4, 19.7.
223
Preparation of (Acetonide){Cou}[G-1]CO2H 18. DMAP (0.18 g, 1.5 mmol) was added to a solution of 17 (5.00 g, 15.0 mmol) and succinic anhydride (1.58 g, 15.8 mmol) in 125 mL of acetonitrile and was refluxed for 18 h. The mixture was cooled, and the solvent evaporated. Chromatography (silica gel, 5% methanol in CH2Cl2) afforded 3.18 g of 18 as a white solid (49 % yield). 1H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 9.00 (broad s, 1 H, NH), 8.87 (s, 1 H, HC=C), 7.69 (m, 2 H, Ar-H), 7.41 (m, 2H, Ar-H), 4.65 (s, 2 H, CH2O2C), 4.29 (d, 2J(H,H) = 12 Hz, 2 H, CH2O), 3.96 (d, 2J(H,H) = 12 Hz, 2 H, CH2O), 2.66 (m, 4 H, CH2-CH2), 1.52 (s, 3 H, CH3), 1.44 (s, 3 H, CH3);
13
C NMR (125 MHz,
CDCl3): δ 175.6, 171.6, 161.7, 161.5, 148.5, 134.3, 129.9, 125.4, 118.6, 118.5, 116.7, 98.9, 63.4, 62.7, 53.2, 28.9, 28.6, 24.2, 22.8.
Preparation of (Acetonide)8{Cou}8[G-1]Porphyrin 19: PS-Carbodiimide obtained from Argonaut Technologies (1.8 g, 2.2 mmol of carbodiimide functional groups) was added to a solution of TDHPP (0.10 g, 0.14 mmol), 18 (0.70 g, 1.6 mmol), DMAP (0.053 g, 0.43 mmol), and dimethylamino-pyridinium p-toluene sulfonic acid (DPTS, 0.13 g, 0.43 mmol) in freshly distilled pyridine (15 mL) at room temperature. The solution was stirred overnight, and the reaction was monitored by MALDI MS. After the coupling was complete, the reaction mixture was filtered, poured into 100 mL CH2Cl2, washed with 1 M NaHSO4, brine, dried over MgSO4, and the solvent evaporated. Chromatography (silica gel, 4% methanol in CH2Cl2) afforded 0.366 g of 19 as a purple solid (65 % yield). 1
H NMR (500 MHz, CDCl3, 25 oC, TMS): δ 9.02 (s, 8 H, CONH), 8.85 (s, 8 H, coumarin
HC=C), 8.65 (s, 8 H, β-H), 7.82 (s, 8 H, porphyrin Ar-H), 7.36 (m, 20 H, coumarin and porphyrin Ar-H), 7.09 (m, 16 H, coumarin Ar-H), 4.64 (s, 16 H CH2CO2), 4.30 (d, 224
2
J(H,H) = 12 Hz, 16 H, CH2O), 3.91 (d, 2J(H,H) = 12 Hz, 16 H, CH2O), 2.97 (t, 3J(H,H)
= 6 Hz, 16 H, CH2-CH2), 2.87 (t, 3J(H,H) = 6 Hz, 16 H, CH2-CH2), 1.46 (s, 24 H, CH3), 1.36 (s, 24 H, CH3).
Preparation of 7-(N-Ethyl-N-t-butyloxycarbonylmethylamino)-4-trifluoromethylcoumarin 20. A mixture of coumarin 500 (0.10 g, 0.39 mmol), t-butyl bromoacetate (0.17 mL, 1.17 mmol), and K2CO3 (0.16 g, 1.17 mmol) in 1 mL of DMF was heated at 110 oC for 6 d. Although additional t-butyl bromoacetate (3 x 0.17 mL, 1.17 mmol) was added, full conversion could not be achieved. Filtration followed by evaporation of the solvent in vacuo and chromatography (silica gel, CH2Cl2) gave 82 mg of 20 as a yellow powder (57 % yield). 1H NMR (500 MHz, CDCl3, 25 °C, TMS): δ 7.52 (dd, 3J (H,H) = 18 Hz, 3 Hz, 1 H, Ar-H), 6.60 (dd, 3J (H,H) = 19 Hz, 2 Hz, 1 H, Ar-H), 6.51 (d, 3J (H,H) = 2 Hz, 1 H, Ar-H), 6.43 (s, 1 H, C=CH), 3.99 (s, 2 H, CH2CO2), 3.53 (q, 3J (H,H) = 7 Hz, 2 H, N-CH2-CH3), 1.47 (s, 9 H, CH3), 1.26 (t, 3J (H,H) = 7 Hz, 3 H, N-CH2-CH3); 13
C NMR (125 MHz, CDCl3): δ 168.7, 160.3, 156.8, 151.5, 141.8, 141.6, 126.2, 122.9,
109.5, 108.9, 108.8, 103.5, 98.5, 82.5, 52.9, 46.8, 28.0, 12.2; Anal. C: 58.35, H: 5.57, N: 3.76 F: 15.15 (calcd C: 58.22, H: 5.43, N: 3.77, F: 15.35).
Preparation
of
7-(N-ethyl-N-methylamino)-4-trifluoromethylcoumarin
21.
Trifluoroacetic acid (0.1 mL) were added to a solution of 7-(N-ethyl-N-t-butyloxycarbonylmethyl)amino-4-trifluoromethylcoumarin (50 mg, 0.14 mmol) in 5 mL of CH2Cl2 and it was stirred for 1 h. After neutralizing the pH with 7 M NH3/MeOH, it was filtered and the solvent evaporated to afford 21 as a bright yellow powder. 1H NMR (500 225
MHz, CDCl3, 25 °C, TMS): δ 7.50 (dd, 3J (H,H) = 18 Hz, 3 Hz, 1 H, Ar-H), 6.65 (dd, 3J (H,H) = 18 Hz, 2 Hz, 1 H, Ar-H), 6.53 (d, 3J (H,H) = 2 Hz, 1 H, Ar-H), 6.39 (s, 1 H, C=CH), 3.49 (q, 3J (H,H) = 7 Hz, 2 H, N-CH2-CH3), 3.04 (s, 3 H, N-CH3), 1.21 (t, 3J (H,H) = 7 Hz, 3 H, N-CH2-CH3);
13
C NMR (125 MHz, CDCl3): δ 160.5, 156.9, 152.1,
141.6, 126.0, 109.4, 108.1, 108.0, 102.7, 98.1, 46.8, 37.6, 11.5; FAB MS: m/z = 272 (calcd for C13H13F3NO2 + 272).
Preparation of 1-Trifluoromethyl-9-hydroxylnaphtho[2,1-b]pyran-3-one 22: To a mixture of 2,7-dihydroxynaphthalene (7.08 g, 44.2 mmol) and ethyl 4,4,4trifluoroacetoacetate (9.7 mL, 66.3 mmol) was added 80 % H2SO4 (40 mL) at 0 oC. The dark colored solution was stirred for another 3 h at room temperature, then 200 mL of ice water were added, and it was stirred for 1 h. Filtration, washing with water, and recrystallization of the residue from 300 mL of ethanol gave 5.91 g of 22 as yellow crystals (48 % yield). 1H NMR (500 MHz, DMSO-d6, 25 oC, TMS): δ 10.35 (s, 1 H, OH), 8.17 (d, 3J (H,H) = 9 Hz, 1 H, Ar-H), 7.94 (d, 3J (H,H) = 8 Hz, 1 H, Ar-H), 7.67 (broad s, 1 H, Ar-H), 7.37 (d, 3J (H,H) = 9 Hz, 1 H, Ar-H), 7.19 (dd, 3J (H,H) = 8 Hz, 4J (H,H) = 2 Hz, 1 H, Ar-H), 7.13 (s, 1 H, Ar-H);
13
C NMR (125 MHz, DMSO-d6): δ 158.3, 157.8,
156.0, 139.8, 139.5, 135.4, 131.4, 129.1, 125.2, 123.7, 121.5, 117.7, 116.9 (q), 113.9, 107.7 (q), 107.3; EI-MS: m/z = 304.3 (calcd for C14H7F3O3Na+ 303.2); Anal. C: 59.84, H: 2.37, F: 20.09 (calcd C: 60.01, H: 2.52, F: 20.34); UV/vis (MeOH) λmax (ε) 364 nm (10000); λem (MeOH) 519 nm.
226
Preparation
of
1-Trifluoromethyl-9-(t-butyloxycarbonylmethyloxy)naphtho[2,1-
b]pyran-3-one 23: 1-Trifluoromethyl-9-hydroxylnaphtho[2,1-b]pyran-3-one 22 (1.00 g, 3.569 mmol) was dissolved in 2 mL of DMF at 80 oC and K2CO3 (0.99 g, 7.138 mmol) was added leading to an immediate appearance of a dark red color. Addition of tbutylbromoacetate (0.79 mL, 5.353 mmol) led to decolorization and it was heated at 80 o
C for another 30 min. Dilution with ethyl acetate, filtration, washing with 1 M NaHSO4,
brine, drying over MgSO4, and evaporation afforded 1.37 g of 23 as a brown powder (97 % yield). (The product can be recrystallized from ethanol.) 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 7.99 (d, 3J (H,H) = 9 Hz, 1 H, Ar-H), 7.84 (d, 3J (H,H) = 9 Hz, 1 H, ArH), 7.72 (d, 4J (H,H) = 2 Hz, 1 H, Ar-H), 7.37 (d, 3J (H,H) = 9 Hz, 1 H, Ar-H), 7.31 (dd, 3
J (H,H) = 9 Hz, 4J (H,H) = 2 Hz, 1 H, Ar-H), 7.01 (s, 1 H, Ar-H), 4.68 (s, 2 H, CH2O),
1.51 (s, 9 H, CH3);
13
C NMR (125 MHz, CDCl3): δ 167.3, 158.8, 158.0, 156.4, 135.1,
131.1, 129.2, 126.9, 118.2, 116.6 (q), 115.4, 108.7, 106.2 (q), 82.8, 65.3, 28.0; Anal. C: 61.05, H: 4.46, F: 14.61 (calcd C: 60.92, H: 4.35, F: 14.45); UV/vis (CHCl3) λmax (ε) 365 nm (10000); λem (CHCl3) 471 nm.
Preparation of 1-Trifluoromethyl-9-(carboxymethyloxy)naphtho[2,1-b]pyran-3-one 24: 1-Trifluoromethyl-9-(t-butyloxycarbonylmethyloxy)naphtho[2,1-b]pyran-3-one 23 (8.44 g, 21.4 mmol) was dissolved in 15 mL of CH2Cl2 and 2 mL of trifluoracetic acid were added. It was stirred at room temperature and during the course of the reaction, the product precipitated. It was filtered and washed with cold CH2Cl2 to get 5.11 g of 24 as a yellow powder (71 % yield). (The product can be recrystallized from ethanol, however ethanol is incorporated into the crystals.) 1H NMR (500 MHz, DMSO-d6, 25 oC, TMS): δ 227
13.21 (broad s, 1 H, COOH), 8.23 (d, 3J (H,H) = 9 Hz, 1 H, Ar-H), 8.05 (d, 3J (H,H) = 9 Hz, 1 H, Ar-H), 7.58 (d, 4J (H,H) = 2 Hz, 1 H, Ar-H), 7.47 (d, 3J (H,H) = 9 Hz, 1 H, ArH), 7.36 (dd, 3J (H,H) = 9 Hz, 4J (H,H) = 2 Hz, 1 H, Ar-H), 7.17 (s, 1 H, Ar-H), 4.82 (s, 2 H, CH2O); 13C NMR (125 MHz, DMSO-d6): δ 169.7, 158.2, 157.6, 156.0, 139.4, 139.1, 135.1, 131.4, 128.4, 126.3, 117.7 (q), 117.0, 115.3, 107.8, 106.2 (q), 64.5; Anal. C: 57.02, H: 2.83, F: 16.66 (calcd C: 56.82, H: 2.68, F: 16.85).
References 1. Gust, D; Moore, T. A.; Moore, A. L. Acc. Chem. Res. 2001, 34, 40. 2. (a) Newkome, G. R.; Moorefield, C. N.; Vögtle, F. Dendritic Molecules: Concepts, Synthesis, Perspectives; VCH: Weinheim, 1996. (b) Top. Curr. Chem. 1998, 197; 2000, 210; 2001, 212. (c) Bosman, A. W.; Jansen, H. M.; Meijer, E. W. Chem. Rev. 1999, 99, 1665. (d) Chow, H.-F.; Mong, T. K.-K.; Nongrum, M. F.; Wan, C.-W. Tetrahedron 1998, 54, 8543. (e) Fréchet, J. M. J.; Hawker, C. J. In Comprehensive Polymer Science, 2nd Suppl.; Aggarwal, S. L.; Russo, S., Eds.; Pergamon Press: Oxford, 1996, p 140. (f) Fréchet, J. M. J. Science, 1994, 263, 1710. (g) Tomalia, D. A.; Naylor, A. M.; Goddard, W. A., III Angew. Chem. Int. Ed. 1990, 29, 138.3. 3. Hecht, S.; Fréchet, J. M. J. Angew. Chem. Int. Ed. 2001, 40, 74. 4. Adronov, A.; Fréchet, J.M.J. Chem. Commun. 2000, 1701. 5. Hecht, S.; Fréchet, J.M.J. J. Am. Chem. Soc. 2001, 123, in press. 6. (a) Bo, Z. S.; Schäfer, A.; Franke, P.; Schlüter, A. D. Org. Lett. 2000, 2, 1645. (b) Freeman, A. W.; Chrisstoffels, L. A. J.; Fréchet, J. M. J. J. Org. Chem. 2000, 65,
228
7612. (c) Schultz, L. G.; Zhao, Y.; Zimmerman, S. C. Angew. Chem. Int. Ed. 2001, 40, 1962. 7. (a) The Porphyrin Handbook; Kadish, K. M.; Smith, K. M.; Guillard, R., Eds.; Academic Press: San Diego, 2000. (b) The Porphyrins; Dolphin, D., Ed.; Academic Press: New York, 1978. (c) Porphyrins and Metalloporphyrins; Smith, K. M., Ed.; Elsevier: New York, 1976. 8. Phthalocyanines; Leznoff, C. C.; Lever, A. B. P., Eds.; VCH: New York, 1989. 9. According to Förster theory, the energy transfer efficiency is dependend on the extinction coefficient of the acceptor chromophore. For detailed discussions consult: (a) Förster, T. Fluoreszenz Organischer Verbindungen; Vandenhoech and Ruprech: Göttingen, 1951. (b) Van der Meer, W. B.; Coker, G., III; Chen, S.-Y. Resonance Energy Tranfer, Theory and Data; VCH: Weinheim, 1994. 10. Hecht, S.; Vladimirov, N.; Fréchet, J. M. J. J. Am. Chem. Soc. 2001, 123, 18. 11. (a) Ihre, H.; Hult, A.; Söderland, E. J. Am. Chem. Soc. 1996, 118, 6388. (b) Ihre, H.; Hult, A.; Fréchet, J.M.J.; Gitsov, I. Macromolecules 1998, 31, 4061. 12. Forbes, D. C.; Ene, D. G.; Doyle, M. P. Synthesis 1998, 879. 13. For the use of hypermonomer building blocks see for instance: (a) Wooley, K. L.; Hawker, C. J.; Fréchet, J. M. J. Angew. Chem. Int. Ed. 1994, 33, 82. (b) L’abbe, G.; Forier, B.; Dehaen, W. J. Chem. Soc., Chem. Commun. 1996, 1262. 14. For naphthopyranone chromophores consult: Langmuir, M. E.; Yang, J.-R. ; Moussa, A. M.; Laura, R.; LeCompte, K. A. Tetrahedron Lett. 1995, 36, 3989.
229
15. For
a
related
synthesis
of
the
naphthopyranone
skeleton
from
2,7-
dihydroxynaphthalene see: Tao, Z.-F.; Qian, X.; Fan, M. Tetrahedron 1997, 53, 13329. 16. Casimir, J. R.; Turetta, C.; Ettouati, L.; Paris, J. Tetrahedron Lett. 1995, 36, 4797. 17. Annby, U.; Malmberg, M.; Pettersson, B.; Rehnberg, N. Tetrahedron Lett. 1998, 39, 3217. 18. James, D. A.; Arnold, D. P.; Parsons, P. G. Photochem. Photobiol. 1994, 59, 441. 19. (a) Kim, J. B.; Adler, A. D.; Longo, F. R. In The Porphyrins; Dolphin, D., Ed.; Academic Press: New York, 1978; Vol. I, Part A, p 85. (b) Rocha Gonsalves, A. M. d’A.; Varejao, J. M. T. B.; Pereira, M. M. J. Heterocyclic Chem. 1991, 28, 635. 20. McOmie, J. F.; Watts, M. W. Tetrahedron 1968, 24, 2289. 21. Van der Pol, J.F.; Neeleman, E.; van Miltenburg, J.C.; Zwikker, J.W.; Nolte, R.J.M.; Drenth, W. Macromolecules 1990, 23, 155. 22. (a) The Porphyrins; Dolphin, D., Ed.; Academic Press: New York, 1978. (b) Porphyrins and Metalloporphyrins; Smith, K. M., Ed.; Elsevier: New York, 1976. 23. Bloomquist, A.T.; Winslow, E. C. J. Org. Chem. 1944, 10, 149. 24. Diels, O.; Thiele, W. E. Justus Liebigs Ann. Chem. 1931, 486, 191. 25. (a) Diels, O.; Thiele, W. E. Chem. Ber. 1938, 71, 1173. (b) Weis, C. D. J. Org. Chem. 1963, 28, 74. (c) Kopranenkov, V. N.; Goncharova, L. S.; Lukyanets, E. A. Zh. Obshch. Khim. 1988, 58, 1055. 26. (a) Wood, J. L.; Khatri, N. A.; Weinreb, S. M. Tetrahedron Lett. 1979, 20, 4907. (b) Mease, R. C.; Hirsch, J. A. J. Org. Chem. 1984, 49, 2925.
230
27. (a) Kopranenkov, V. N.; Rumyantseva, G. I. Zh. Obshch. Khim. 1975, 45, 1521. (b) Oliver, S. W.; Smith, T. D. J. Chem. Soc., Perkin Trans. II 1987, 1579. (c) Oliver, S. W.; Smith, T. D.; Hanson, G. R.; Lahy, N.; Pilbrow, J. R.; Sinclair, G. R. J. Chem. Soc., Faraday Trans. 1 1988, 84, 1475.
231
Chapter 9:
Exploring
Alternative
Polymer
Architectures
–
Towards
Photocatalytic Monoliths
Abstract Light-harvesting chromophores, coupled to energy-converting photocatalytic sites, were successfully incorporated into a monolith matrix that possesses advantageous mechanical properties. Efficient energy transduction was observed and experiments investigating the catalytic performance of the monoliths are currently in progress. The design benefits from its simplicity that could lead to the practical construction of flowthrough photoreactors.
232
Introduction Although the dendritic architecture is ideally suited to design multifaceted systems capable of mimicking both light harvesting and conversion, as described in the previous chapter, the preparation of such complex molecules becomes increasingly more difficult. In order to simplify the synthesis and therefore enhance the practicality of such lightdriven catalytic systems, it is desirable to explore accelerated routes that implement all necessary functions into alternative polymer backbones. Monolithic materials1 have been identified as ideal candidates due to their convenient preparation and possible use in flow-through applications. In general, monolithic polymers are highly cross-linked, macroporous supports that have been used as polymeric reagents and scavengers in combinatorial chemistry as well as chromatographic separation media.2 Their preparation, involving polymerization of the monomer mixture in bulk in the presence of appropriate porogens, has been carried out within various geometric confinements allowing applications as membranes, capillaries, and in lab-on-chip devices. Due to their unique pore size distribution resulting in high mass transfer, rigid monoliths have shown promise as potential flow-through heterogeneous catalyst supports.3 It should be noted that monolithic materials have so far not been explored with regard to optical applications. In this chapter, progress toward the design of photoresponsive catalytic monoliths is described. The approach involves preparation of porous monolithic polymer matrices incorporating donor chromophores as well as functional handles that are modified with catalytic moieties (Figure 9.1). External flow provided by a conventional pump is used
233
rather than internal flow generated by the amphiphilic ‘pump’ as in the case of the dendritic design (see previous chapters). hν O O
O O O
hν ' HO
OH
O
O
O
ET
N
O
O
O O
O
N
O
Pd
O O
O
N N
N H
ET
O O O
O O
O
O
O O
O O
O
hν Figure 9.1. Illustration of the concept of light-harvesting photocatalytic monoliths. A methacrylate-based polymer matrix, incorporating coumarin donor chromophores, is functionalized with a palladium porphyrin derivative. Energy harvesting and transfer followed by singlet oxygen generation lead to efficient photooxygenation.
Results and Discussion The monolith preparation involved radical copolymerization of a various monomers in the presence of varying amounts of 1-dodecanol and dimethyl sulfoxide as porogens (Scheme 9.1). The monomer mixture consisted of the transparent matrix (54 % methyl methacrylate), the cross-linking agent (39.5 % ethylene dimethacrylate) the donor chromophores (5 % coumarin-labeled ethyl methacrylate 1), and the handle necessary for post-functionalization (0.5 % aminoethyl methacrylate hydrochloride). Optimization of the polymerization conditions allowed for control over the pore size distribution and therefore reasonable flow rates through monolithic capillaries. The prepared monoliths 2 were post-functionalized either with free base porphyrin 3 for spectroscopic 234
characterization to afford monoliths 5 or with palladium complex 4 for catalysis experiments to give monoliths 6. Scheme 9.1 CO2H
O O O
O
O
N
O
O O
O
O O
O
O
O
O
AIBN O
60 oC (porogen)
NH3+Cl-
O
3 (M=H2) 4 (M=PdII)
O
DIC, DMAP rt, (THF)
O
O O
O O
O
O
O
O
O
1
O
O
O
O
O
O
O O
O
O
NH3+Cl-
O
O
O O
O
O
O
O
O
O O
O
O
O
O O
N
O O
O
O
N M
N
O
O O
HN
O
O
2 N
N M
N
N
5 (M=H2) 6 (M=PdII)
Characterization of the materials was performed on bulk samples and involved reflectance absorption and emission spectroscopies. Unfunctionalized monoliths 2 showed the expected absorption of the coumarin-3-carboxylate chromophore, while functionalized monolith 5 exhibited absorption bands for both the coumarin as well as the porphyrin chromophores (Figure 9.2). Interestingly, the Q-band absorption associated with the porphyrin is enhanced in the monolithic material as compared to solution. While free base porphyrin chromophores allow for further characterization by fluorescence spectroscopy, their corresponding palladium complexes do not fluoresce due to extremely
235
efficient intersystem crossing that in fact is the reason for their superior ability to sensitize singlet oxygen. Therefore, absorption spectroscopy has proven very useful to characterize monoliths 6 as illustrated in Figure 9.3, which shows the characteristic Q-band (~525 nm) of the palladium porphyrin. b)
absorbance
a)
300
400
500
600
700
300
400
500
600
700
wavelength / nm
wavelength / nm
absorbance
Figure 9.2. Absorption spectra of a) monolith samples 2 (........) and 5 (____); as well as b) individual chromophores methyl coumarin-3-carboxylate (........) and tetraphenylporphyrin (____) in CHCl3.
300
400
500
600
700
wavelength / nm
Figure 9.3. Absorption spectra of monolith 6 (_____) and the corresponding precursor 4 (..........) in CHCl3.
Subsequently, fluorescence experiments to evaluate the energy transfer efficiency were carried out on bulk monolith samples in the absence and the presence of the free base acceptor porphyrin (Figure 9.4). Monoliths 2 showed the expected coumarin
236
emission centered around 420 nm. However, when the coumarin donor chromophores in monoliths 5 were selectively excited their emission was significantly quenched and the porphyrin acceptor fluorescence was enhanced, indicating efficient energy transfer. The shape of the coumarin emission band further suggest some contribution of trivial energy transfer.4 Generally, the energy transfer efficiency is governed by the average donor acceptor distance and therefore, the ratio monomer ratio can in principle be optimized to
corrected fluorescence intensity
achieve more efficient energy transfer and light harvesting.
400
450
500
550
600
650
700
wavelength / nm Figure 9.4. Emission spectra of monolith samples 2 (..........) and 5 (_____).
Encouraged by these results, for the first time documenting energy transfer in monolithic materials in general, ongoing efforts are involving polymerizations in silica coated capillaries followed by post-functionalization using palladium complex 4 to afford monoliths 6 for flow-through catalysis experiments.
237
Conclusion A general approach to incorporate light-harvesting chromophore pairs in combination with singlet oxygen sensitizers in rigid monolithic materials has been developed. Efficient energy transfer within the monoliths could be demonstrated and lays the foundation for future investigation of their catalytic performance. The simplicity of the design and the overall practicality of the approach potentially allow for the construction of photoresponsive flow-through reactors in a variety of formats.
Experimental General Methods: All reagents were used as received and without further purification, unless otherwise noted. THF was distilled under N2 over sodium/benzophenone prior to use. Column chromatography was carried out with Merck silica gel for flash columns, 230-400 mesh. NMR spectra were recorded on a Bruker AMX-300 (300 MHz) instrument with TMS or solvent carbon signal as the standards. Electronic absorption spectra were recorded on a Cary 50 UV-Visible Spectrophotometer for solutions samples and a Cary 400 Bio UV/Vis Spectrometer (diffuse reflectance mode) for bulk polymer samples. Fluorescence spectra were measured either of degassed solutions (1cm cells, ODmax < 0.1) or bulk polymer samples (in reflectance mode) using an ISA/SPEX Fluorolog 3.22 equipped with a 450 W Xe lamp, double excitation and double emission monochromators, and a digital photon-counting photomultiplier. Correction for variations in lamp intensity over time and wavelength was achieved with a solid-state silicon photodiode as the reference. The spectra were further corrected for variations in photomultiplier response over wavelength and for the path difference between the sample 238
and the reference by multiplication with emission correction curves generated on the instrument. Porosity measurements were preformed on an Autopore III 9400 mercury porosimeter.
General Procedure for Coumarin Monolith (2) Preparation:5 2,2-Azoisobutyronitrile (AIBN, 0.012 g, .007 mmol) was added to a mixture of 1 (0.06 g, 0.20 mmol), methyl methacrylate (MMA) (0.65 g, 6.5 mmol), aminoethyl methacrylate hydrochloride (AEMA) (0.007 g, 0.04 mmol), and ethylene dimethacrylate (EDMA) (0.48 g, 2.4 mmol) in a 60 % w/w solution of the appropriate porogen. The resulting homogenous mixture was sonicated and purged with nitrogen for 5 min. The fused silica capillary (50, 100, or 1000 µL internal diameter: Polymicro Technologies, Phoenix, AZ) was washed consecutively with 0.1 M sodium hydroxide, water, 0.1 M hydrochloric acid, water, and then acetone. The treated capillary was filled with a 30 wt.% 3-(trimethoxysilyl)propyl methacrylate solution in acetone, the ends sealed with pieces of rubber tubing, and allowed to react at room temperature for 12 h. The capillary was then washed with acetone, and dried in a stream of nitrogen. The polymerization mixture was drawn into a 250 µL syringe and its outlet attached through a Teflon tube sleeve to a 0.5-1 m long piece of the previously modified capillary. The capillary was filled with the polymerization mixture, and its ends were sealed. The remainder of the mixture was sealed within a glass vial. The polymerization proceeded in a 60 oC bath for 20 h. The resulting monolith containing capillary was washed overnight with methanol using a µHPLC pump. The glass vial containing the monolith formed from the bulk polymerization mixture was carefully crushed, the polymer cut into small pieces, Soxhlet 239
extracted with methanol for 12 h to remove any soluble compounds, and vacuum dried at room temperature overnight. This polymer 2 was used for porosity measurements and characterization using UV/vis and emission spectroscopies.
General Procedure for Monolith Functionalization: The bulk polymers were immersed in a solution of porphyrin monoacid 3 or its palladium complex 4 (1 equiv.) in THF containing 1.1 equiv. 1,3-diisopropylcarbodiimide (DIC) and 10 mol% 4-dimethylaminopyridine (DMAP) for 12 h. The polymers 5 and 6 were then washed exhaustively with THF for 2 days and used for characterization using UV/vis and emission spectroscopies.
Preparation of 2-(coumarin-3-carboxy)ethyl methacrylate 1. Coumarin-3-carboxylic acid (4.0 g, 21 mmol) was suspended in 50 mL CH2Cl2 and oxalyl chloride (2.75 mL, 31.5 mmol) added. After addition of a catalytic amount of DMF (3 drops) the reaction mixture started to reflux and was held at reflux temperature for 2 h. Evaporation of the solvent and drying in vacuum afforded the coumarin-3-carboxylic acid chloride, which was dissolved in 30 ml CH2Cl2 and slowly added to a solution of 2-hydroxyethyl methacrylate (2.30 mL, 18.9 mmol), DMAP (0.26 g, 2.1 mmol), and triethylamine (4.75 mL, 31.6 mmol) in 20 ml CH2Cl2 at 0 oC. After stirring for 1 h, and standing in the refrigerator,
the
reaction
mixture
was
filtered
and
the
solvent
evaporated.
Chromatography (silica gel, 40% ethyl acetate in hexanes) afforded 5.5 g of the product as slowly crystallizing white needles (96 % yield). 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 8.53 (s, 1 H, cou =CH-), 7.70-7.61 (m, 2 H, cou Ar-H), 7.38-7.33 (m, 2 H, cou 240
Ar-H), 6.18-6.16 (m, 1 H, =CH2), 5.62-5.60 (m, 1 H, =CH2), 4.63-4.58 (m, 2 H, OCH2), 4.53-4.48 (m, 2 H, CH2O), 1.96 (broad s, 3 H, CH3);
13
C NMR (125 MHz, CDCl3): δ
167.11, 162.61, 156.44, 155.29, 148.95, 135.81, 134.54, 129.57, 126.25, 124.86, 117.74, 117.67, 116.79, 63.38, 62.07, 18.25; EI-MS: m/z 325.05 (M+Na+, C16H14O6Na requires 325.07); Anal. C: 63.63, H: 4.62 (calcd C: 63.57, H: 4.67); UV/vis (CHCl3) λmax (ε) 294 nm (13650), 335 nm (7190).
Preparation of 5-(4’-carboxyphenyl)-10,15,20-triphenylporphyrin 3.6 5-(4’-Carboxymethylphenyl)-10,15,20-triphenylporphyrin
was
prepared
heating
a
mixture
of
benzaldehyde (3.81 mL, 37.5 mmol), methyl 4-formylbenzoate (2.05 g, 12.5 mmol), and pyrrole (3.47 mL, 50 mmol) in 150 mL propionic acid/nitrobenzene (5:1) at 120 oC. After standing overnight, the solvent was removed in vacuo, and the product isolated using chromatography (30 % hexanes in ethyl acetate) to give 1.19 g of the methyl ester as a dark purple powder (14 % yield). The ester (0.50 g, 0.74 mmol) was saponified by refluxing a mixture of 100 mL 2 M NaOH and 100 mL ethanol for 24 h. The solution was acidified using acetic acid and after centrifugation and drying in vacuum, 3 was obtained as a purple powder in quantitative yield (490 mg). The characterizational data of the methyl ester as well as the acid 3 agree with the literature.6
Preparation of palladium(II) 5-(4’-carboxyphenyl)-10,15,20-triphenylporphyrin 4. Conversion to the corresponding palladium complex 7 was achieved by refluxing a mixture of 3 (1 equiv.) with 1.5 equiv. palladium(II) acetate in 10 mL of CHCl3 and 2 mL of MeOH for 14 h. Dilution with 10 mL of CH2Cl2 followed by extraction with water and 241
brine, drying over Na2SO4, and chromatography (10 % MeOH in CH2Cl2) gave the desired complex 4 in quantitative yield. Note that the product is non-fluorescent. 1H NMR (300 MHz, CDCl3, 25 oC, TMS): δ 8.85-8.77 (m, 8 H, β-H), 8.52 (d, 3J (H,H) = 8 Hz, 2 H, Ar-H), 8.32 (d, 3J (H,H) = 8 Hz, 2 H, Ar-H), 8.17 (d, 3J (H,H) = 6 Hz, 6 H, ArH), 7.78-7.73 (m, 10 H, Ar-H); EI-MS: m/z 759.74 (M-H+, C45H27N4O2Pd requires 761.12); UV/vis (CHCl3) λmax (ε) 417 (238000), 524 (21600), 555 (2500), 605 (1400) nm.
References 1. (a) Svec, F.; Fréchet, J. M. J. Anal. Chem. 1992, 64, 820. (b) Fréchet, J. M. J.; Svec, F. US Patent 5334310 1994. 2. For a review consult: Peters, E. C.; Svec, F.; Fréchet, J. M. J. Adv. Mater. 1999, 11, 1169. 3. (a) Petro, M.; Svec, F.; Fréchet, J. M. J. Biotechnol. Bioeng. 1996, 49, 355. (b) Park, T. G.; Hoffman, A. S. Appl. Biochem. Biotechnol. 1988, 19, 1. (c) Xie, S.; Svec, F.; Fréchet, J. M. J. Biotechnol. Bioeng. 1999, 62, 30. (d) Altava, B; Burguete, M. I.; Fraile, J. M.; García, J. I.; Luis, S. V.; Mayoral, J. A.; Vicent, M. J. Angew. Chem. Int. Ed. 2000, 39, 1503. 4. Hecht, S.; Vladimirov, N.; Fréchet, J. M. J. J. Am. Chem. Soc. 2001, 123, 18. 5. Sykora, D.; Peters, E. C.; Svec, F.; Fréchet, J. M. J. Macromol. Mater. Eng. 2000, 275, 42. 6. (a) Huang, D.; Matile, S.; Berova, N.; Nakanishi, K. Heterocycles 1996, 42, 723. (b) Matile, S.; Berova, N.; Nakanishi, K.; Fleischhauer, J.; Woody, R. W. J. Am. Chem. Soc. 1996, 118, 5198. 242
