Benzyl Chloride-Functionalized Polycarbonates: A Versatile Platform ...

Article pubs.acs.org/Macromolecules

Benzyl Chloride-Functionalized Polycarbonates: A Versatile Platform for the Synthesis of Functional Biodegradable Polycarbonates Robert J. Ono,† Shao Qiong Liu,‡ Shrinivas Venkataraman,‡ Willy Chin,‡ Yi Yan Yang,‡ and James L. Hedrick*,† †

IBM Almaden Research Center, 650 Harry Road, San Jose, California 95120, United States Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore 138669, Singapore

‡

S Supporting Information *

ABSTRACT: An aliphatic polycarbonate containing pendant benzyl chloride groups was synthesized by organocatalytic ring-opening polymerization (ROP) of a cyclic carbonate monomer (MTC− OCH2BnCl). Facile postpolymerization modification of the resultant polymer with various nucleophiles facilitated access to a functionally diverse variety of polycarbonate materials in high yield, including those that contained diethanolamine, phosphonium, and azide groups. The azide-functionalized polycarbonates could be further elaborated via Cu-catalyzed click chemistry with alkynyl-functionalized poly(ethylene glycol) (PEG) or pyrene to form the corresponding PEG- or pyrenegrafted polymers. Finally, an amphiphilic block copolymer containing grafted pyrene units in the hydrophobic block was synthesized using the aforementioned postpolymerization click functionalization strategy. We show by transmission electron microscopy (TEM) and light scattering that the block copolymer self-assembles into micelles of ∼48 nm diameter in aqueous media and that the critical micelle concentration (CMC) of the nanoparticles was lower than that exhibited by similarly sized micelles formed from a control block copolymer containing no pyrene (CMC values of 6.3 and 8.1 mg L−1, respectively).

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INTRODUCTION Aliphatic polycarbonates have emerged as a popular class of synthetic materials for applications in polymer-based nanomedicine, owing to their biodegradability, low toxicity, and biocompatibility. These polycarbonates are most conveniently synthesized via ring-opening polymerization (ROP) of the corresponding cyclic carbonate monomers, for which a variety of anionic, cationic, enzymatic, metal-catalyzed, and organocatalyzed methods are available.1−7 Copolymers of poly(trimethylene carbonate) (PTMC), the structurally simple aliphatic polycarbonate synthesized by ROP of the cyclic monomer trimethylene carbonate (TMC), have already found use in commercial applications as degradable suture materials under the trade name Maxon.8,9 For many biomedical applications, however, synthetic polymers including polycarbonates must interact with bioactive molecules such as drugs, peptides, and proteins in a specific fashion to perform their intended function (e.g., as a delivery vehicle for micellar drug delivery). This necessitates the use of polycarbonates containing functionalities that are capable of covalent (or supramolecular) attachment to biologically active molecules. Toward this end, significant efforts have been directed toward synthesizing functional polycarbonates containing various chemically reactive moieties, including allyl,10 propargyl,11 hydroxyl,12,13 amine,14,15 carboxyl,16 boronic acid,17 and vinyl sulfone groups,18 to name a few. © 2014 American Chemical Society

Pendant chemical functionality can be introduced into polycarbonates via polymerization of the corresponding functional cyclic monomers or via postpolymerization modification of a reactive precursor polymer.19 In general, direct polymerization of functional monomers is surely the simplest, most straightforward way to introduce functionality to a polymer; however, postpolymerization functionalization strategies can prove advantageous if the desired functional groups are incompatible with the polymerization reaction. Furthermore, postpolymerization modification allows for a single precursor polymer to be elaborated into libraries of functional polymers having similar average molecular weights and molecular weight dispersities, thereby facilitating the study of structure−property relationships.20 Postpolymerization functionalization of aliphatic polycarbonates requires the selection of a monomer containing a reactive functional group that is inert to the ROP conditions yet can react quantitatively under mild conditions with a variety of molecules to introduce diverse functionality to the polymer. Because of the relatively fragile nature of the polycarbonate backbone, postpolymerization functionalization reactions involving aliphatic polycarbonates must also preclude polymer degradation. Received: August 22, 2014 Revised: October 14, 2014 Published: November 3, 2014 7725

dx.doi.org/10.1021/ma501734y | Macromolecules 2014, 47, 7725−7731

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Scheme 1. Organocatalyzed Ring-Opening Polymerization of MTC−OCH2BnCl

Scheme 2. Postpolymerization Functionalization of Poly(MTC−OCH2BnCl) with Primary and Secondary Amines

antimicrobial polymers by virtue of its good stability and shelf life and high reactivity toward a number of quaternizing agents including tertiary amines39 and phosphines40 as well as nitrogen heterocycles.39 In light of these prior results and the electrophilicity of benzyl halide groups in general, we reasoned that poly(MTC−OCH2BnCl) could facilitate entry to the synthesis of a large variety of functional polycarbonates via postpolymerization functionalization. Herein we disclose our findings on the reaction of poly(MTC−OCH2BnCl) with various small molecule nucleophiles and evaluate its utility as a reactive polycarbonate platform from which a diverse array of tailored, functionality-rich polycarbonates can be synthesized.

In view of the aforementioned criteria, functional groups associated with “click chemistry” have emerged as excellent chemical handles for polycarbonate postpolymerization modification. Indeed, alkene-,10,21 alkyne-,22−25 and azide26,27functionalized cyclic carbonates have been successfully polymerized by ROP. These precursor polymers could be subsequently reacted with respective thiol-, azide-, or alkynecontaining molecules via thiol−ene chemistry or 1,3-dipolar cycloaddition, respectively, to afford a variety of functional materials. Polycarbonates containing activated ester moieties have also been used as precursor materials for postpolymerization modification.28 Recently, we reported29 the acid-catalyzed ROP of activated pentafluorophenyl ester-functionalized cyclic carbonates,30 the resulting polymers of which are amenable to facile postpolymerization functionalization with amines31 and alcohols32 at room temperature with little to no degradation of the polycarbonate backbone. As part of our ongoing program in nanomedicine, we have explored the use of cationically charged polycarbonates in applications ranging from macromolecular antimicrobials to antifouling coatings.33−38 Synthetically, cationic polycarbonates are typically accessed by postpolymerization modification of pendant alkyl halide-functionalized polycarbonates with quaternizing agents, such as tertiary amines. One such polycarbonate containing reactive pendant benzyl chloride groups, poly(MTC−OCH 2 BnCl), has become a particularly useful intermediate for the synthesis of highly potent cationic

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RESULTS AND DISCUSSION The polymer precursor used for our studies, poly(MTC− OCH2BnCl), was synthesized via metal-free organocatalytic ROP of the benzyl chloride-functionalized carbonate monomer MTC−OCH2BnCl, as we have previously reported (Scheme 1).39 Briefly, MTC−OCH2BnCl, MPA−OCH2Tol, and a catalytic amount of 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) and N-(3,5-trifluoromethyl) phenyl-N′-cyclohexylthiourea (TU) (5 mol % of each with respect to monomer) were stirred in dichloromethane at room temperature for 30 min, which afforded poly(MTC−OCH2BnCl) as a white solid in 85% yield upon precipitation and washing in cold methanol. As a result of the controlled nature of the organocatalyzed ROP reaction, polymers with predictable average chain lengths were 7726


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obtained by varying the initial monomer-to-initiator feed ratios. Homopolymer degrees of polymerization (DP) were verified by 1 H NMR spectroscopy, by integrating the signal intensity of the methyl protons of the diol initiator (i.e., MPA−OCH2Tol) at 2.31 ppm against that of the benzylic protons located on the polymer side chains at 5.12 ppm (CDCl3). For example, polymerization with a targeted DP of 50 (i.e., initial monomerto-initiator feed ratio of 50:1) yielded a poly(MTC− OCH 2 BnCl) homopolymer with a DP of around 48, corresponding to a number-average molecular weight (Mn) of 14.2 kDa. Gel permeation chromatography (GPC) was also performed on the obtained poly(MTC−OCH2BnCl), which revealed a narrow dispersity (Đ) of 1.2 and an Mn of 13.6 kDa, in good agreement with that determined by 1H NMR analysis. With the benzyl chloride-functionalized polymer precursor in hand, we shifted our attention toward investigating its postpolymerization functionalization with various nucleophiles. Given its previously established reactivity toward tertiary amines to afford quaternary ammonium-functionalized polycarbonates,39 we were interested in whether poly(MTC− OCH2BnCl) was amenable to primary and secondary amine alkylation as well. Predictably, treatment of poly(MTC− OCH2BnCl) with equimolar amounts of a primary amine such as allylamine in the presence of triethylamine as the base led to cross-linked products due to overalkylation (Scheme 2). When poly(MTC−OCH2BnCl) was treated with a stoichiometric amount of diethanolamine in the presence of N,N′diisopropylethylamine (DIPEA), however, we observed successful alkylation to the corresponding tertiary amine by 1H NMR spectroscopy, as evidenced by an upfield shift of the benzylic protons adjacent to the chloro group on the starting polymer from 4.70 to 3.66 ppm (DMSO-d6), in addition to the appearance of new signals attributable to the diethanolamine group. Furthermore, the diethanolamine-functionalized poly(MTC−OBnDEA) exhibited excellent solubility in water, in stark contrast to its precursor poly(MTC−OCH2BnCl), which is completely insoluble in aqueous environments. The ability to confer hydrophilicity to a hydrophobic polycarbonate through postpolymerization modification may find utility in the synthesis of biodegradable amphiphilic block copolymers for applications such as drug delivery. We recently reported on the antibacterial properties of phosphonium-functionalized cationic polycarbonates synthesized via the reaction of poly(MTC−OCH2BnCl) with trimethylphosphine.40 The promising antibacterial activity of the trimethylphosphonium-functionalized polycarbonates, along with the commercial availability of many different tertiary phosphines, prompted us to further explore the reactivity of poly(MTC−OCH2BnCl) toward phosphonium salt formation. To determine whether phosphine alkylation was general for poly(MTC−OCH2BnCl), several tertiary phosphines were reacted with the polymer under otherwise similar conditions (Scheme 3). As summarized in Table 1, all of the phosphines tested formed the corresponding polymer-bound phosphonium chloride salts by simple stirring with poly(MTC−OCH2BnCl) in acetonitrile at 50 °C. In all cases, equimolar concentrations of the phosphine with respect to the number of benzyl chloride groups led to incomplete conversions after 18 h. Using a 2-fold excess of the phosphine, however, resulted in quantitative or near-quantitative conversion to the phosphonium salt in the same time span, although longer reaction times were necessary for the reaction of triphenylphosphine (PPh3) with poly(MTC−OCH2BnCl) (Table 1, entry 6), presumably due to the

Scheme 3. Phosphonium Salt Formation by Reaction of MTC−OCH2BnCl with a Tertiary Phosphine

Table 1. Reaction of Poly(MTC−OCH2BnCl) with Various Tertiary Phosphines To Form the Corresponding Phosphonium-Functionalized Poly(MTC−OCH2BnPR3Cl)a entry 1 2 3 4 5 6

PR3 R R R R R R

= = = = = =

Bu Bu Oct Oct Ph Ph

equiv of PR3

time (h)

convb (%)

1 2 1 2 1 2

18 18 18 18 42 42

50 100 (73) 77 100 (83) 76 95 (93)

Reaction conducted in acetonitrile at 50 °C. bDetermined by 1H NMR spectroscopy. Isolated yields in parentheses. a

reduced nucleophilicity of PPh3 relative to that of the trialkylphosphines that were tested. Regardless, precipitating the reaction mixtures into ethyl ether removed any excess phosphine and afforded the pure phosphonium-functionalized polymers in good yields (73−93%). Collectively, these results show that several phosphonium-functionalized cationic polycarbonates can be easily synthesized via one step postpolymerization modification of poly(MTC−OCH2BnCl) and, given the large number of tertiary phosphines that are commercially available, further imply that new classes of phosphoniumfunctionalized polycarbonates are readily accessible. Studies on the antibacterial properties of these and related novel cationic polycarbonates are currently underway but fall outside of the scope of this paper and will be reported in due course. We subsequently explored postpolymerization transformation of poly(MTC−OCH2BnCl) into azido-functionalized polymers for further functionalization via Cu-catalyzed azide− alkyne cycloaddition (CuAAC). Click chemistry, and in particular the CuAAC reaction, has been utilized in the postpolymerization modification of aliphatic polycarbonates due to its atom economy and high yielding nature under mild reaction conditions22,24,41 as well as its compatibility with a wide range of readily available azide- or alkyne-functionalized coupling partners. Both azido-27 and propargyl-functionalized22−25 polycarbonates have been reported. In one example, Zhuo and co-workers reported the polymerization of 2,2bis(azidomethyl)trimethylene carbonate and its subsequent functionalization via CuAAC with a variety of alkynes.26 While the authors did report that the aforementioned monomer was safe to handle according to established tests for impact-sensitive materials, the extremely high nitrogen content in the molecule (and its polymeric isomer) nonetheless connotes a high risk of explosive decomposition. We therefore reasoned that an alternative strategy involving postpolymerization modification of poly(MTC−OCH2BnCl) into an azide-containing polycarbonate would be of value because (1) an azide-modified 7727


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chloro groups to azido groups had occurred. We subsequently explored the coupling of poly(MTC−OCH2BnN3) with alkynes using click chemistry. Briefly, an alkyne-functionalized pyrene or poly(ethylene glycol) monomethyl ether (mPEG) was stirred with poly(MTC−OCH2BnN3) in the presence of copper sulfate and sodium ascorbate in DMSO at 50 °C (Scheme 4). Analysis of the recovered materials by FT-IR and 1 H NMR spectroscopy showed the disappearance of the azide signal at ∼2100 cm−1 and the presence of proton signals attributable to both coupling partners in the sample, respectively, suggesting that the CuAAC reaction had taken place as expected. Unfortunately, a lack of solubility of either sample in THF precluded analysis via GPC using THF as eluent, which we speculated was, at least in the case of the reaction involving pyrene, due to polymer aggregation brought about by π-stacking of the pendant pyrene units.42 Therefore, in order to mitigate this aggregation effect and thus improve the solubility of the resultant polymer, a copolymer containing a reduced number of azide repeat units per polymer chain was synthesized via random copolymerization and subsequent azidation of MTC−OCH2BnCl and benzyl-functionalized MTC-OBn (Scheme 5). As expected, reaction of this copolymer using the aforementioned CuAAC conditions afforded soluble products that could be characterized by FTIR, 1H NMR spectroscopy, and GPC. As shown in Figure 1, GPC analysis of the azide-functionalized copolymer before and after reaction with propargyl pyrene (i.e., poly(MTC−OBn-coMTC−OCH2BnN3) and poly(MTC−OBn-co-MTC-graf t-Pyr), respectively) using refractive index (RI) detection revealed a shift of a single, monomodal signal to shorter retention times, confirming that the polymer backbone remained intact during the click reaction. Furthermore, the GPC traces of poly(MTC− OBn-co-MTC-graf t-Pyr) obtained using RI detection and UV− vis detection at 350 nma wavelength absorbed by pyrene but not by the azide-functionalized precursor copolymerare nearly perfectly superimposed, thus confirming that the pyrene units are covalently attached to the polymer. These results, together with the FT-IR and 1H NMR characterization data (see Supporting Information), suggested that the postpolymerization modification of poly(MTC−OCH2BnCl) (and its derivatives thereof) using CuAAC was indeed successful. In order to demonstrate the utility of the above-mentioned postpolymerization modification reactions, a pair of amphiphilic

poly(MTC−OCH2BnCl) should be more stable toward violent decomposition than poly(2,2-bis(azidomethyl)trimethylene carbonate) by virtue of its significantly lower nitrogen content relative to the number of carbon and oxygen atoms compared to that of the latter and (2) it minimizes the overall number of synthetic transformations, from start to finish (i.e., from monomer synthesis to CuAAC modification of polymer), that require the handling of an organic azide. Treatment of poly(MTC−OCH2BnCl) with sodium azide in DMF at room temperature afforded the azide-functionalized polymer poly(MTC−OCH2BnN3) in 83% isolated yield (Scheme 4). A significant upfield shift of the 1H NMR signal Scheme 4. Azide Postpolymerization Modification of Poly(MTC−OCH2BnCl) and Subsequent Cu-Catalyzed 1,3Dipolar Cycloaddition with Alkynes

attributable to the benzylic protons from 4.55 to 4.31 ppm (CDCl3), coupled with the appearance of a strong signal at ∼2100 cm−1 in the infrared (FT-IR) spectrum (see Supporting Information), suggested that quantitative conversion of the

Scheme 5. Postpolymerization Modification of a Polycarbonate Copolymer by Cu-Catalyzed 1,3-Dipolar Cycloaddition with Alkynes

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micellization, the increased hydrophobic and π−π stacking interactions of covalently attached pyrene units would lead to a more tightly bound hydrophobic micelle core as compared to the micelles containing no pyrene, resulting in a measurable change in the critical micelle concentration (CMC) as a function of pyrene content. To form the micelles, DMF solutions of the polymers (initial concentration: 5 mg mL−1) were dialyzed against deionized water. As shown in Table 2, micelles ca. 50 nm in hydrodynamic diameter were formed for both diblock copolymer samples, as expected, given their similar molecular weights and ratio of hydrophobic/hydrophilic blocks. Figure 2 shows TEM images of micelles made from the two block copolymers. Both polymers formed very well-defined spherical micelles. It is noted that the particle size of PEG-bpoly(MTC−OBn) and PEG-b-poly(MTC-graft-Pyr) estimated from TEM were ∼25 and ∼15 nm in diameter, respectively. These figures are smaller than those obtained by DLS analysis due to dehydration of micelles after TEM sample preparation. CMC values of 8.1 and 6.3 mg L−1 were measured for PEG-bpoly(MTC−OBn) and PEG-b-poly(MTC-graf t-Pyr), respectively, corresponding to a 27% decrease. As the only major structural differences between PEG-b-poly(MTC−OBn) and PEG-b-poly(MTC-graf t-Pyr) are the two pyrene units (per polymer chain) that are attached to the latter polymer, we attribute the decrease in the CMC value to the increased hydrophobic and/or π−π stacking interactions in the micellar core facilitated by the pendant pyrene side chains.

Figure 1. Normalized GPC traces of poly(MTC−OBn-co-MTC− OCH2BnN3) and poly(MTC−OBn-co-MTC-graf t-Pyr) using RI detection (black and blue, respectively) and the latter using UV−vis detection at 350 nm (red dash).

diblock copolymers was synthesized and self-assembled into micelles. As shown in Scheme 6, the amphiphilic diblock copolymers were synthesized via ROP of either MTC−OBn or a mixture of MTC−OBn and MTC−OCH2BnCl using mPEG as the initiator. Treatment of the benzyl chloride containing block copolymer with sodium azide and further functionalization with pyrene under the aforementioned click conditions afforded PEG-b-poly(MTC-graf t-Pyr). This yielded two block copolymers, one containing pyrene (PEG-b-poly(MTC-graf tPyr)) and one without (PEG-b-poly(MTC−OBn)), having similar molecular weights and weight fractions of the hydrophilic segment (i.e., PEG). We hypothesized that, upon

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CONCLUSION We have herein described the organocatalyzed ROP of MTC− OCH2BnCl and its subsequent postpolymerization functionalization with a number of small molecule nucleophiles.

Scheme 6. Postpolymerization Modification of an Amphiphilic Diblock Copolymer by Cu-Catalyzed 1,3-Dipolar Cycloaddition with Propargylated Pyrene

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Table 2. Physical Properties of Diblock Copolymer Micelles sample

CMCa (mg L−1)

Dhb (nm)

polydispersity

zeta potential (mV)

wPEGc

PEG-b-poly(MTC-OBn) PEG-b-poly(MTC-graf t-Pyr)

8.1 6.3

49.6 ± 0.6 47.9 ± 0.5

0.20 ± 0.01 0.23 ± 0.01

−0.01 ± 0.47 −0.21 ± 0.16

0.65 0.60

a

1

CMC determined by dynamic light scattering (DLS). bHydrodynamic diameter as determined by DLS. cWeight fraction of PEG as determined by H NMR spectroscopy. (3) Kiesewetter, M. K.; Shin, E. J.; Hedrick, J. L.; Waymouth, R. M. Macromolecules 2010, 43, 2093−2107. (4) Kobayashi, S. Macromol. Rapid Commun. 2009, 30, 237−266. (5) Varma, I. K.; Albertsson, A.-C.; Rajkhowa, R.; Srivastava, R. K. Prog. Polym. Sci. 2005, 30, 949−981. (6) Dove, A. P. ACS Macro Lett. 2012, 1, 1409−1412. (7) Nederberg, F.; Lohmeijer, B. G. G.; Leibfarth, F.; Pratt, R. C.; Choi, J.; Dove, A. P.; Waymouth, R. M.; Hedrick, J. L. Biomacromolecules 2007, 8, 153−160. (8) Metz, S. A.; Chegini, N.; Masterson, J. B. Biomaterials 1990, 11, 41−45. (9) Noorsal, K.; Mantle, M. D.; Gladden, L. F.; Cameron, R. E. J. Appl. Polym. Sci. 2005, 95, 475−486. (10) Tempelaar, S.; Mespouille, L.; Dubois, P.; Dove, A. P. Macromolecules 2011, 44, 2084−2091. (11) Pratt, R. C.; Nederberg, F.; Waymouth, R. M.; Hedrick, J. L. Chem. Commun. 2008, 114−116. (12) Fukushima, K.; Pratt, R. C.; Nederberg, F.; Tan, J. P. K.; Yang, Y. Y.; Waymouth, R. M.; Hedrick, J. L. Biomacromolecules 2008, 9, 3051−3056. (13) Parzuchowski, P. G.; Jaroch, M.; Tryznowski, M.; Rokicki, G. Macromolecules 2008, 41, 3859−3865. (14) Venkataraman, S.; Veronica, N.; Voo, Z. X.; Hedrick, J. L.; Yang, Y. Y. Polym. Chem. 2013, 4, 2945−2948. (15) Sanda, F.; Kamatani, J.; Endo, T. Macromolecules 2001, 34, 1564−1569. (16) Bartolini, C.; Mespouille, L.; Verbruggen, I.; Willem, R.; Dubois, P. Soft Matter 2011, 7, 9628−9637. (17) Aguirre-Chagala, Y. E.; Santos, J. L.; Aguilar-Castillo, B. A.; Herrera-Alonso, M. ACS Macro Lett. 2014, 3, 353−358. (18) Wang, R.; Chen, W.; Meng, F.; Cheng, R.; Deng, C.; Feijen, J.; Zhong, Z. Macromolecules 2011, 44, 6009−6016. (19) Tempelaar, S.; Mespouille, L.; Coulembier, O.; Dubois, P.; Dove, A. P. Chem. Soc. Rev. 2013, 42, 1312−1336. (20) Gauthier, M. A.; Gibson, M. I.; Klok, H.-A. Angew. Chem., Int. Ed. 2009, 48, 48−58. (21) He, F.; Wang, C.-F.; Jiang, T.; Han, B.; Zhuo, R.-X. Biomacromolecules 2010, 11, 3028−3035. (22) Shi, Q.; Chen, X.; Lu, T.; Jing, X. Biomaterials 2008, 29, 1118− 1126. (23) Shi, Q.; Huang, Y.; Chen, X.; Wu, M.; Sun, J.; Jing, X. Biomaterials 2009, 30, 5077−5085. (24) Han, Y.; Shi, Q.; Hu, J.; Du, Q.; Chen, X.; Jing, X. Macromol. Biosci. 2008, 8, 638−644. (25) Li, T.-h.; Jing, X.-b.; Huang, Y.-b. Polym. Adv. Technol. 2011, 22, 1266−1271. (26) Zhang, X.; Zhong, Z.; Zhuo, R. Macromolecules 2011, 44, 1755− 1759. (27) Zhu, W.; Wang, Y.; Zhang, Q.; Shen, Z. J. Polym. Sci., Part A: Polym. Chem. 2011, 49, 4886−4893. (28) Zhou, Y.; Zhuo, R.-X.; Liu, Z.-L. Macromol. Rapid Commun. 2005, 26, 1309−1314. (29) Engler, A. C.; Chan, J. M. W.; Coady, D. J.; O’Brien, J. M.; Sardon, H.; Nelson, A.; Sanders, D. P.; Yang, Y. Y.; Hedrick, J. L. Macromolecules 2013, 46, 1283−1290. (30) For other polymer backbones bearing pendant pentafluorophenyl esters, see: (a) Nilles, K.; Theato, P. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 3683−3692. (b) Gibson, M. I.; Fröhlich, E.; Klok, H.-A. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 4332−4345. (c) Li, Y.; Duong, H. T. T.; Jones, M. W.; Basuki, J. S.; Hu, J.; Boyer, C.; Davis, T. P. ACS Macro Lett. 2013, 2, 912−917.

Figure 2. TEM images of aqueous micellar solutions of (A) PEG-bpoly(MTC−OBn) and (B) PEG-b-poly(MTC-graft-Pyr). Concentration: 1 mg mL−1.

Specifically, the modification of poly(MTC−OCH2BnCl) with diethanolamine, tertiary phosphines, and sodium azide was successfully demonstrated. The CuAAC click chemistry of benzyl azide-functionalized polycarbonate was also explored and was used to modulate the CMC of polycarbonate-based amphiphilic block copolymer micelles. This result demonstrates that the aforementioned postpolymerization modification reactions can be utilized to fine-tune polymer architecture, which can in turn influence their self-assembly for use in applications such as the delivery of hydrophobic drugs in vivo. Given the versatility that poly(MTC−OCH2BnCl) offers as a synthetic intermediate, we believe that it, along with the postpolymerization functionalization methodologies described here, will find utility in the preparation of functional polycarbonates for a host of biomedical applications.

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ASSOCIATED CONTENT

S Supporting Information *

Experimental procedures and additional characterization data. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (J.L.H.). Funding

IBM Almaden Research Center (U.S.A.) and Institute of Bioengineering and Nanotechnology (Biomedical Research Council, Agency for Science, Technology and Research, Singapore). Notes

The authors declare no competing financial interest.

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REFERENCES

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