based water-soluble block copolymers

SYNTHESIS, CHARACTERISATION AND EVALUATION OF NOVEL METHACRYLATEBASED WATER-SOLUBLE BLOCK COPOLYMERS

by Vural Bütün

Submitted to the University of Sussex in fulfillment of the requirements for the award of Doctor of Philosophy September 1999

Contents

DECLARATION

The work described in this thesis was carried out at the University of Sussex between January 1996 and September 1999, under the supervision of Dr. S. P. Armes. Unless stated otherwise, it is the work of the author and has not been submitted in whole or in part for any other degree at this or any other university.

September 1999

Signed ………………………………

Vural Bütün

School of Chemistry, Physics and Environmental Science, University of Sussex, Falmer, Brighton, BN1 9QJ

ACKNOWLEDGEMENT

ii

Contents

Firstly I would like to thank my supervisor, Steve Armes, and Norman Billingham for all their help and guidance. I would also like to thank them for giving me the opportunity to visit Australia, the USA, Turkey, Czech Republic and many places around England. Especially I would like to thank my sponsor university, Osmangazi University in Turkey, for giving me the opportunity to do PhD in abroad. Thanks must also go to Dr. Maria Vamvakaki for initial technical advice on the synthesis and characterisation of the (co)polymers. I also wish to thank Franco Unali for giving me the professor seniority (!) since 1996.

Various people helped with the work in this thesis and other publications. Many thanks to Dr. Zdenek Tuzar from the Institute of Macromolecular Chemistry in Prague. At Sussex University Dr Julian Thorpe is thanked for the electron microscopies and his help in trying to teach me how to use TEM and to get a decent image. Chris Dadswell is specially thanked for running all my proton NMR samples (20 samples a day!). I would like to thank all the people in mechanical workshop, the electronics workshop and stores.

I also wish to thank all the people I have worked with in the Lab, past and present, including Andy, Stuart, Dean, Rob, Jane, Clive, Akif, Lindsey, David, Emma A, Emma L, Matt, Frederic etc. etc... There are others in the department of course, but too many to mention, so I will stop there. The school of Chemistry, Physics and Environmental Science is thanked for funding this work.

Last and certainly not least, I wish to thank my wife Hanife and my son Buðra for all their love, support and faith in me, throughout bad times as well as the good.

THE UNIVERSITY OF SUSSEX Vural Bütün

Submitted for D.Phil

iii

Contents

Synthesis, Characterisation and Evaluation of Novel Methacrylate-Based Water-Soluble Block Copolymers ABSTRACT Group transfer polymerisation has been used to prepare a series of water-soluble (co)polymers of narrow molecular weight distribution based on tertiary amine methacrylates. 2-(dimethylamino) ethyl methacrylate (DMA) was block copolymerised in turn with three other tertiary amine methacrylate comonomers, namely 2-(diethylamino)ethyl methacrylate (DEA), 2-(diisopropyl amino)ethyl methacrylate (DPA) and 2-(N-morpholino)ethyl methacrylate (MEMA). A series of diblock copolymers, DMA-MEMA, DMA-DEA and DMA-DPA, with molecular weights ranging from 1x103 g mol-1 to 5x104 g mol-1 and with DMA contents varying systematically from 20 to 80 mol % were synthesized. In order to obtain block copolymers of suitable composition, and hence micellisation behaviour, a series of each homopolymers were also synthesized and their solubility in water investigated. All homopolymers and block copolymers had narrow molecular weight distributions (Mw/Mn 300oC).

1.3.2 Poly(4-styrenesulfonic acid)

Poly(4-styrenesulfonic acid) (PSSA) (see Figure 1.4) can be prepared by classical free radical polymerisation of the free acid, or the sodium/potassium salt.40 It is also possible to produce PSSA via living anionic polymerisation of styrene, followed by sulfonation.41

7

Chapter 1. Introduction

Due to hygroscopic character of the free acid, PSSA salts are the preferred form for longterm storage and handling.40 Atactic PSSA is soluble in water, methanol, and ethanol, and insoluble in hydrocarbons. In the salt form it is only soluble in water.40

1.4 CATIONIC WATER-SOLUBLE POLYMERS

1.4.1 Poly(2-(dimethylamino)ethyl methacrylate)

Poly[2-(dimethylamino)ethyl methacrylate] (PDMA) (see Figure 1.5) is a weak polybase which is water-soluble in both neutral and acidic media due to protonation of the tertiary amine groups. PDMA becomes insoluble when the solution temperature is increased (> 32 oC). In its quaternised form no cloud-point behaviour is observed and the polymer remains soluble up to 100oC. Recently several research groups have described the synthesis of well-defined, near-monodisperse copolymers based on DMA via living polymerisation techniques. Among these, Hoogeveen et al. described the synthesis and adsorption behaviour of a range of diblock copolymers comprising DMA and 2,3dihydroxypropyl methacrylate (DHPM).42 These copolymers were prepared via classical anionic polymerisation using protecting group chemistry for the DHPM residues. It was found that these copolymers adsorbed onto acidic silica particles via the basic DMA residues. Subsequent flocculation of the silica sol was explained in terms of charge neutralisation of the anionic silica by the cationic DMA residues and the poor steric stabilisation properties imparted by the DHPM block. The same workers also reported the use of such copolymers as both stabilizers and flocculants for oxide particles43 and compared the adsorption of DMA and quaternised DMA homopolymers onto both colloidal silica and titania particles.44 Nagai et al.45 have described the aqueous polymerisation of DMA quaternised with lauryl bromide in the presence of silica gel. High yields of silica encapsulation were achieved when the feed ratio of monomer to silica was 0.13 by weight or less. Under these conditions most of the monomer is adsorbed onto the anionic silica surface. Creutz et al. described the controlled polymerisation of three basic monomers using classical anionic techniques: DMA,46 4vinylpyridine47,48 and tert-butylaminoethyl methacrylate49. Zwitterionic diblock and triblock copolymers comprising DMA and sodium methacrylate were also prepared,

8


using tert-butyl methacrylate as a protected monomer for the sodium methacrylate residues. The kinetics of unimer-micelle exchange of these naphthalene-labelled block copolymers, and also a series of related analogues, were studied by fluoresence spectroscopy using a pyrene probe.50,51 The related DMA-ammonium methacrylate zwitterionic diblock copolymers were claimed to have some potential as universal pigment dispersants, since a range of inorganic oxides and organic dyes could be readily dispersed in aqueous media over a wide pH range.52 This was attributed to the ubiquitous adsorption characteristics imparted by the DMA residues. DMA-based copolymers with N-vinylpyrrolidone (NVP),53-56 N-phenylmaleimide,57 ethylene,58 methacrylic acid59 and

terpolymers of DMA with MMA and 2-hydroxyethyl methacrylate60 (HEMA) have also been reported by many groups using conventional free-radical polymerisation chemistry. Copolymers of DMA with MMA have been prepared by γ-ray irradiation and studied as potential carbon dioxide sensors by Yokouchi et al.61

Poly(2-vinylpyridine)

[

CH

CH2

]n

Poly(Nisopropylacrylamide)

[

N

CH2

]n

CH

C=O

Poly(2-(dimethylamino)ethyl methacrylate) CH3

[

CH2

C

]n

C=O NH H3 C Poly(4-vinylpyridine)

[

CH

CH2

]n

C

O CH3

CH2

Poly (vinyl amine) [ CH CH2 ] n

NH2

CH2 N H3C

CH3

N

Figure 1.5 Chemical structure of some typical cationic water-soluble polymers.

Tagagishi et al. and Kozuka et al. have reported that DMA homopolymer and DMA-Nvinylpyrrolidone (NVP) copolymers were efficient binders of methyl orange and octyl orange and the fluorescent probe 2-p-toluidinylnaphthalene-6-sulfonate (TNS).62,63 DMA-NVP copolymers exhibited a very pronounced binding affinity for the polymer

9


probe. The degree of binding to methyl orange was examined as a function of copolymer composition, pH and ionic strength. The extent of binding increased with the content of the DMA in the copolymer, relatively. Maximum binding was observed with DMA homopolymer at pH 8. At lower pH, the degree of binding was reduced.

DMA-based hydrogels, which are biocompatible, have been reported by Prausnitz and co-workers.64-66 These were synthesised to investigate swelling properties and kinetics as a function of pH, added buffer and buffer pKa. They reported that hydrogels comprising 25-30 mol% DMA in buffered solutions swelled as the solution pH lowered, since this increases the mobile ion concentration inside the hydrogels due to protonation of tertiary amine residues and hence raises the ionic osmotic pressure.65 Blezer et al.67 have studied cross-linked DMA hydrogels and compared these to networks of polyethylene and poly(vinyl chloride). These latter materials are biocompatible but suffer from platelet adhesion. It was found that the level of platelet adhesion in the DMA hydrogel was significantly lower than that observed for polyethylene. In order to eliminate protein adsorption from tears on the surface of contact lenses, DMA-based hydrogels were studied by Sassi et al.68 Lysozyme did not adsorb onto the gel between pH 7.2-8.0; this was attributed to electrostatic repulsion between the cationic protein and the charged cationic DMA residues. The synthesis of quaternised DMA-based (co)polymers has been reported by several groups either by direct polymerisation of quaternised DMA monomer or by modification of the DMA residues after polymerisation. Yasuda et al.69 polymerised a series of alkyl bromide-quaternised DMA monomers in both aqueous media and benzene at 60oC. Similarly, a series of DMA monomer quaternised with alkyl bromides of varying chain lengths were polymerised in both aqueous and organic media.70,71 Bogoeva-Gaceva and Andonova investigated solvent effects on the rate of polymerisation of quaternised DMA.72 DMA monomer was first quaternised with dimethyl sulfate. It was found that the rates

of

polymerisation

decreased

with

decreasing

solvent

polarity,

e.g.

H2O>DMSO>DMF>EtOH. Quaternised DMA-based hydrophilic-hydrophobic statistical and block copolymers including styrene,73 MMA,74 BzMA and BuMA75 have also been synthesised by several workers.

10


At Sussex Baines et al. prepared a series of DMA-MMA block copolymers76 by group transfer polymerisation (GTP) and examined their efficacy as steric stabilisers in the dispersion polymerisation of styrene in alcoholic media.77 The micellisation behaviour of these hydrophilic-hydrophobic diblocks in aqueous solution was studied using both static and dynamic light scattering and analytical ultracentrifugation.78 In colloboration with Baines and coworkers, Thomas’s group have recently published a series of neutron reflectivity studies of the analogous selectively deuterated DMA-MMA copolymers adsorbed at the air-water interface.79-82 Lowe et al.83,84 have prepared zwitterionic DMAMAA diblock copolymers similar to those reported by Creutz et al. After exploring various protecting groups for the methacrylic acid residues, 2-tetrahydropyranyl methacrylate was found to be best suited for the synthesis of well-defined blocks since it was readily removed by acid hydrolysis under mild conditions. These DMA-MAA copolymers dissolved molecularly in aqueous media at 20oC but formed large micellar aggregates at elevated temperature. These block copolymers also behaved like synthetic proteins, with reversible precipitation occurring at a certain critical pH (the isoelectric point) in aqueous solution. Patrickios et al.85-86 have attempted to exploit this phenomenon in order to isolate, and hence purify, neutral proteins. Lowe et al. have also demonstrated

that

near-monodisperse

DMA

homopolymers87

and

DMA-alkyl

methacrylate block copolymers88,89 can be quantitatively derivatised under remarkably mild conditions using 1,3-propane sultone. In 1997 Nagasaki et al. reported that, contrary to conventional wisdom, heteroatom methacrylates such as 2-(diethylamino)ethyl methacrylate (DEA) can be polymerised with good livingness using simple potassium alcoholate-based initiators in THF at or above room temperature.90 The Sussex group have recently extended this work in order to prepare styrene-functionalized macromonomers based on DMA and various other tertiary amine methacrylates.91 These well-defined macromonomers can be used as model reactive stabilisers to prepare polystyrene latexes via both aqueous emulsion and nonaqueous dispersion polymerisation. Furthermore, monomethoxy-capped poly(ethylene oxide) (MPEO) can be readily converted into the corresponding potassium alcoholate macro-initiator, which can be used to prepare novel MPEO-DMA diblock copolymers.92

11


These copolymers, and their related analogues, are currently being evaluated as synthetic vectors for gene therapy applications.93 1.4.2 Poly(vinylpyridines)

Poly(2-vinylpyridine) (P2VP) and poly(4-vinylpyridine) (P4VP) (see Figure 1.5) are weak polyelectrolytes, which are water-soluble in acidic media in their ionised (or protonated) form, but are insoluble at neutral pH. Both P2VP and P4VP may be synthesised from their monomers via both free radical and living anionic polymerisation techniques.94-97 2-vinypyridine has been anionically polymerised in the early 1960s.97 On the other hand, anionic polymerisation of 4VP was carried out in the early 1990s.98 Recently, Creutz et al. reported that the homopolymerisation of 4VP at 0oC in 9:1 pyridine:THF had ‘living’ character.47 The same group also block copolymerised 4VP with tert-butyl methacrylate.47 Several groups have also reported the synthesis of vinylpyridine-based diblock copolymers by polymerising vinylpyridines with either hydrophobic monomers such as styrene,99,100 tert-butyl acrylate101 or dimethyl siloxane98 or hydrophilic monomers such as PEO101,102 or DMA.53,55 P2VP and P4VP can be quaternised to form strong cationic polyelectrolytes using alkyl halides.53,55,94-98,103,104 Quaternised poly(vinylpyridine)s are used in anion-exchange resins as flocculants, and also as stabilisers for emulsion polymerisation in acidic media. Copolymers of vinylpyridines with PAA and PMAA are used as coating materials for pharmaceuticals.13 1.4.3 Poly(N-isopropylacrylamide)

Poly(N-isopropylacrylamide) (PNiPAM) (see Figure 1.5) exhibits a sharp phase transition (cloud-point) at around 32oC in aqueous solution.105-108 N-isopropylacrylamide may be polymerised by conventional free radical polymerisation109 or an unusual ceric ion redox system which seems to exhibit living character.26,110,111 The thermosensitive behaviour of PNiPAM has promoted interest in producing membranes, capsules, and gels with temperature-sensitive permeability characteristics.112-115 When it is copolymerised with other monomers, the cloud-point shifts depending on the nature of the comonomer. In addition, addition of an electrolyte leads to higher cloud points.116 Recently, both Lee et al.117 and Topp et al.26 synthesised block copolymers of PNiPAM and PEO [PNiPAM-

PEO] and studied their critical micelle temperatures26 and their cloud-points117 in aqueous media. The aggregation of block copolymer microgels of PNiPAM and PEO has

12


been studied by Zhu and Napper.110 They clamed that these block copolymer microgels exhibited uniques colloidal behaviour. Yoo et al.109 synthesised NiPAM-acrylic acid copolymers and investigated the effect of polymer complex formation on the cloud point. The cloud point was strongly affected by the solution pH, the presence of electrolyte and the acrylic acid content in the copolymer, as expected.

1.4.4 Poly(vinyl amine)

Poly(vinyl amine) (PVAm) (see Figure 1.5) is water-soluble even in its non-ionised form. Like poly(vinyl alcohol), PVAm cannot be synthesised by direct polymerisation of the vinyl amine monomer, since the monomer has not been isolated. Thus, PVAm is synthesised indirectly using precursor polymers such as polyacrylamide,10 poly(vinyl phthalimide) or poly(tert-butyl N-vinyl carbamate) (see Figure 1.6).40 The synthesis of PVAm.HCl from acrylic acid has also been reported.118

nCH2 = CH

Δ I

.

[

CH2

CH

]n

C=O

C=O

NH2

NH2

NaOCl NaOH

[

CH2

CH

]n

NH2

Figure 1.6 The synthesis of poly(vinyl amine), using a precursor amine monomer.

PVAm has strong basic character (pKb ~ 4)119 and it is usually stored as a hydrochloride salt. In this form it is readily water-soluble but is insoluble in non-aqueous solvents. PVAm is used in photographic applications, as a dye receptor in synthetic fibres, and as a salt-forming compound with penicillin in order to prolong its therapeutic effect.13

1.5 POLYMERISATION CHEMISTRY 1.5.1 Living Polymerisation Systems

A living polymerisation is a chain polymerisation that proceeds in the absence of chain transfer and termination reactions. The polymerisation proceeds until all of the monomer has been consumed; further addition of monomer results in continued polymerisation.

13


These ‘living’ characteristics provide a powerful tool for the synthesis of copolymers with precise architectures. In addition, polymers with predictable molecular weights and narrow molecular weight distributions are obtained. Well-defined block and graft copolymers, as well as star, comb and macrocyclic polymers, and end-functionalised polymers may also be synthesised by living polymerisation. The potential importance, both academic and industrial, of such tailor-made (co)polymers is well-documented in the literature.120,121

The term ‘living’ was first introduced in the 1950’s by Szwarc et al. who reported anionic polymerisations free of side reactions,122 although the existence of such systems had been postulated 20 years earlier by Ziegler.123 Since Szwarc’s initial discovery there has been great progress in the field of living polymerisation. Living cationic124 and living free radical125-127 polymerisation chemistry have been developed in the 1980’s and 1990’s, respectively. This has led to many different classes of living polymers which have numerous applications, as summarised in Figure 1.7. A number of review articles have been produced covering living anionic,128 cationic,129,130 group transfer131 and radical polymerisation.132,133

For a system to be ‘living’ initiation must be faster than the propagation step; if this were not the case then the first chains to be formed would be necessarily longer than chains formed at a later stage. A classical living polymerisation generally requires just an initiator and monomer, e.g. the anionic polymerisation of styrene, ethylene oxide and dienes. Living cationic, atom transfer radical polymerisation and group transfer polymerisation (GTP) require an additional reagent as a catalyst. Living polymerisations have a number of certain characteristics which distinguish them from more conventional polymerisations: •

The formation of narrow molecular weight distribution polymers (Mw/Mn < 1.2)

•

The number-average degree of polymerisation, Mn = [monomer]0/[initiator]0, and Mn increases in a linear fashion with respect to conversion.

•

Ki >>> Kp i.e. no chain growth (propagation) occurs until initiation is complete.

•

The active centres are sufficiently stable to enable the synthesis of block copolymers via sequential monomer addition.

14


•

If the above criteria are fulfilled, a (co)polymer with a Poisson molecular weight distribution will result.

Figure 1.7 Various

(co)polymer

architectures which are accessible by living

polymerisation techniques.134

The major disadvantage of living polymerisations is that in most cases the reaction conditions required are very rigorous. All glassware must be completely moisture-free,

15


chemical reagents need to be carefully purified and dried, with polymerisations generally performed under an inert atmosphere using high vacuum lines and Schlenk line techniques. 1.5.2 Living Anionic Polymerisation

Living anionic polymerisation has been largely used to polymerise styrenic, (meth)acrylic, alkylene oxide and diene monomers.135 Initiating systems for anionic polymerisations can be alkali metals, aromatic complexes of alkali metals, or organoalkali compounds. The two classic initiating species are n-butyl lithium (n-BuLi) and sodium naphthalenide (see Figure 1.8). n- BuLi produces a monofunctional (poly)styryl anion with lithium counterion.

C4H9Li

+

C4H9

CH2 = CH

CH2

CH Li

Figure 1.8 The initiation of styrene with n-butyllithium.

Alternatively, the reaction between sodium naphthalene and styrene yields a bifunctional initiator which may be used to form ABA triblock copolymers, (see Figure 1.9).

. Na

.

2 CH2

⊕

CH Na

.

H2C = CH

CH2

CH Na ⊕ +

+

⊕

⊕

Na

CH

CH2

CH2

CH Na

⊕

ABA Triblock Copolymer

Figure 1.9 The initiation of styrene with a bifunctional initiator derived from sodium

naphthalene.

16


Compared to styrenic monomers, the anionic polymerisation of polar monomers such as (meth)acrylates is complicated by side-reactions. The initiators and anionic chain ends tend to attack the polar carbonyl groups (see Figure 1.10). In addition to a cyclic termination reaction, acrylate polymerisation suffers from further chain transfer and termination reactions since both the carbonyl groups and the α-hydrogen of the acrylates are susceptible to attack by the anionic chain ends. Thus polymers with broad molecular weight distributions, and low conversions are often obtained.

CH 2

C

CH 3 _

δ

C R

CH 3 ⊕

δ

CH 2

C

+ C

O

O

O

_ CH 3 O

R CH 3

Figure 1.10 Attack at ester carbonyl by a nucleophile, leading to destruction of the

initiating species.

These side reactions may be eliminated by modifying the synthesis conditions, i.e. using polar solvents, low temperatures, bulky initiators and large counterions. For example, by carrying out polymerisations in tetrahydrofuran at -75oC using cumylcaesium as initiator.136-139 Inorganic electrolytes such as lithium chloride have also been used to stabilise the anionic living ends. Lithium chloride forms a μ3-complex with the living end and allows the controlled polymerisation of (meth)acrylates up to -20oC.140 Wang et al.141 reported that alkyl aluminium compounds improved the livingness of the anionic polymerisation of methyl methacrylate initiated with various alkyl lithium reagents in pyridine and pyridine/toluene mixtures at or above 0oC. Alternatively, bulky complexes prepared from n-butyllithium, iso-butylaluminium and 2,6-di-tert-butyl(4-methyl)phenol are effective initiators for the polymerisation of methyl methacrylate.142 Using n-butyl lithium as initiator it is also possible to control stereoregularity of the methacrylates. The polymer tacticity depends on the solvent polarity, with isotactic-rich polymers being obtained in non-polar solvents and syndiotactic-rich polymers being favoured in polar media. Other factors include the bulkiness of the (meth)acrylate ester group (sterically hindered esters promote isotacticity) and the polymerisation temperature (higher temperatures lead to the formation of atactic polymer).138

17


Anionic polymerisation has been used to produce functionalised methacrylate polymers. Amphiphilic copolymers containing epoxy and either acidic and/or basic residues have been synthesised, using protecting group chemistry where necessary.143-146 Both 1,3-butadiene and isoprene are readily polymerised using n-butyl lithium initiator to give living polymers largely through a 1,2-polymerisation.134 Manufacture of styrenebutadiene-styrene, ABA triblock copolymers, is currently carried out on an industrial scale for the manufacture of thermoplastic elastomers.134

The ring-opening anionic polymerisation of alkylene oxides, especially ethylene oxide and propylene oxide, represents one of the most extensively studied living systems. PEO and PPO have been polymerised to give homopolymers, and more importantly diblock (PEO-PPO) and triblock copolymers (PEO-PPO-PEO), with narrow molecular weight distributions. Yang et al.147 have synthesised triblock copolymers of the PEO-PPO-PEO type using the dipotassium salt of dipropylene glycol as initiator. These PEO-PPO-PEO triblock copolymers are commercially available from BASF under the commercial name “Pluronics” and also by ICI under the commercial name of “Synperonics”. Luo et al. have synthesised similar triblock copolymers using butylene oxide in place of propylene oxide using the potassium salt of diethylene glycol as initiator, and their properties with respect to micellisation and drug release were extensively studied.148

1.5.3 Group Transfer Polymerisation

Webster et al. developed ‘group transfer polymerisation’ (GTP)149,150 in the early 1980’s. GTP allows the living polymerisation of acrylic monomers, especially methacrylates, at ambient or elevated temperature. In this method, initiation involves the Michael addition of monomer to a silyl ketene acetal initiator.151 This monomer initiator adduct rapidly adds more monomer via repeated Michael-type addition, to form polymer chains. The term ‘GTP’ was used to indicate transfer of the silyl group from the terminal unit of the growing end of the chain to the incoming monomer during propagation. Desilylation of the living chain end with a proton source or removal of the nucleophilic catalyst terminated the polymerisation process. GTP is illustrated in Figure 1.11 for MMA. High molecular weight near-monodisperse polymers (up to 100,000) can be formed at room

18


temperature in quantitative yield.152 As with all “living” polymerisations, molecular weight is controlled by the molar ratio of monomer to initiator. The living character of GTP also allows block copolymer syntheses with narrow molecular weight distributions via sequential monomer addition. Once monomer conversion is completed, the silyl

ketene acetal group at chain ends remain active, and the addition of another suitable monomer may result in block copolymer formation. Depending on the initiator used in the polymerisation, it is possible to obtain AB and ABA block copolymers. GTP is not particularly sensitive to temperature, reactions may be performed below, at or above ambient, even up to ~100oC. However, unwanted side reactions increase with increasing temperature. The polymerisation is exothermic, hence the onset of reaction may be detected by a temperature rise; the heat of polymerisation can be dissipated by allowing low boiling solvents to reflux. CO2Me Me

OSiMe3

Me

OMe

Me

_ Nu

+

Me Me

CO2CH3 _ Nu

OCH3

m MMA

Me

CO2CH3 Me

OSiMe3

Me

OSiMe3

CH2 CO2CH3 m Me

Me

OMe

Figure 1.11 Proposed GTP mechanism using MMA as a monomer

1.5.3.1 GTP Monomers.

Although GTP is particularly suitable for the polymerisation of acrylates and methacrylates, it is also applicable to ketones,149 lactones,153 (meth)acrylonitriles,153 N,Ndimethylacrylamide149,153 and polyunsaturated esters such as ethyl sorbate.154 Suitable methacrylate

monomers

include:

methyl

methacrylate,

2-(dimethylamino)ethyl

methacrylate,74 ethyl methacrylate,155 n-decyl methacrylate,155 tert-butyl methacrylate, benzyl methacrylate,37 2-(N-morpholino)ethyl methacrylate,155 2-tetrahydropyranyl methacrylate,85 glycidyl methacrylate149 and n-butyl methacrylate.149 Functional monomers such as methacrylic acid or 2-hydroxyethyl methacrylate cannot be used in

19


GTP since their labile protons terminate the polymerisation. In order to polymerise such monomers the functional groups need to be masked using protecting groups that are readily converted back to the functional species after the polymerisation. Suitable protecting groups (see Figure 1.12) for MAA include tert-butyl38,156 (1), trimethylsilyl150 (2), benzyl37,85 (3) or 2-tetrahydropyranyl157,158 (4). The trimethylsilyl group (5) is also

the most commonly used protecting group in the polymerisation of HEMA via GTP.153 The polymerisation of acrylates is 100 times faster than methacrylates159 but polymers with broad molecular weight distributions (Mw/Mn > 2.0) are generally obtained. This is presumably due to the α proton which has acidic character and can terminate the polymerisation during propagation. To some extent these problems can be overcome using Lewis acid catalysts.

CH3

[

CH2

C

]n

_R

CH3

[

CH2

C

]n

(1) R = -C(CH3)3 (2) R = -Si(CH3)3

C=O

C=O

(3) R = -CH2-

OR

OH

(4) R =

O

(5) R = -CH2CH2 OSi(CH3)3

Figure 1.12 Possible protecting groups for the synthesis of PMAA by GTP

1.5.3.2 GTP Catalysts.

Since silyl ketene acetals are relatively unreactive in GTP, catalysts are required in order to activate these initiators. Typical nucleophilic GTP catalysts reported by the Du Pont group149

include

cyanides,

fluorides,

bifluorides,

azides,

oxyanions

and

bioxyanions.153,160-162 Of these, TASHF2 gave the best results in the early GTP literature. Bifluorides are not soluble in THF, thus acetonitrile is normally used as a solvent. This leads to complications for the GTP of methacrylates. Alternative counterions have also been employed, and include tetrabutylammonium, tetraethylammonium and potassium. On the other hand, a new class of GTP catalysts based on oxyanions and bioxyanions was developed by Dicker et al.161,163 The major advantage of these catalysts is their solubility in THF, the most commonly used solvent in GTP. The bioxyanions are less active than

20


the corresponding monooxyanions, and give more monodisperse polymers. Additional advantages are their non-hygroscopic nature and ease of preparation. Tetra-n-butyl ammonium bibenzoate (TBABB) (I) has been claimed to have the best catalytic behaviour164-165 and thus it was used as the catalyst in the present study.

O O C H+ C O O

⊕

N[(CH2)3CH3]4

(I) An alternative class of catalysts are Lewis acids153,166 such as HgI2, zinccloride, bromide, and iodide and dialkyl aluminium chlorides and oxides. These catalysts are preferred in the synthesis of narrow molecular weight distribution polyacrylates. However, high levels of catalyst (100-200 times higher than anion-type catalysts) are required for the complete conversion of monomer to polymer. Zinc halides perform best at ambient temperature; the best molecular weight control was obtained with zinc iodide at 20oC while the aluminium-based catalysts work best at –78oC.166 HgI2 is the most effective Lewis acid catalyst for acrylate polymerisations.167

1.5.3.3 GTP Initiators.

The most common initiators for GTP are the silyl ketene acetals, which are easily prepared using procedures reported by Ainsworth et al.168 The most commonly used initiator of this group is 1-methoxy-2-methyl-1-trimethylsiloxy-1-propene (MTS) (1), which is structurally similar to the propagating centre in the GTP of methyl methacrylate (MMA). H3 C

OSi(CH3)3

H3C

OSi(C 2H5)3

H3 C

OCH3

H3C

OCH3

(1)

(2)

H3C

OSi(CH 3)2C18H37

H3C

OSi(CH)2C(CH3)3

H3C

OCH3

H3C

OCH3

21


(3)

(4)

Figure 1.13 Structures of various silyl ketene acetals capable of initiating GTP. Sogah et al.153 have reported initiators (2)-(4) with different alkyl groups attached to the

silicon atom (see Figure 1.13). Similar molecular weight control and polydispersities were obtained for methyl or ethyl substituents on silicon. However, initiators containing a long alkyl group (-C18H37), such as (3), lead to broad molecular weight distribution polymers with poor molecular weight control. On the other hand, if the TASHF2 catalysed polymerisation of MMA using initiator (1) is compared to the same polymerisation using MTS higher molecular weights than expected and broad molecular weight distributions were obtained. This difference was attributed to isomerisation of initiator (1). The rate of isomerisation of MTS is considerably slower.

Me3

SiMe 3

O

O

O

OSiMe 3

OSiMe 3

OSiMe 3

(6)

(7)

(5)

Figure 1.14 Structures of various different cyclic silyl ketene acetal initiators for GTP.

Certain cyclic silyl ketene acetals such as (5) also initiate GTP effectively,153 (see Figure 1.14). In contrast, compound (6) was found to be a poor initiator. Initiator (7) performed somewhat better, providing that a using bifluoride catalyst was employed.

H3C

OSi(CH3)3

H3C

OSi(CH3)3

H3C

OCH2CH2OSi(CH 3)3

H3C

OSi(CH3)3

(8)

(9)

Me3SiO Me

Me

Me

(CH2)n

(10) n = 1

OSiMe 3 OMe

(11) n = 2

22


Figure 1.15 Structures of various bifunctional silyl ketene acetals capable of initiating

GTP. Several bifunctional silyl ketene acetal initiators (8-11) have also been reported for GTP (see Figure 1.15). Their main advantage is to produce propagating chains growing at both ends, which is particularly advantageous for ABA triblock copolymer syntheses. For example, Yu et al.169 has used 1,5-dimethoxy-2,4-dimethyl-1,5-bis-[(trimethylsilyl)oxy]1,4-pentadiene (10) and 1,6-dimethoxy-2,4-dimethyl-1,6-bis-[(trimethylsilyl)oxy]-1,5hexadiene (11) to copolymerise MMA with n-butyl methacrylate and allyl methacrylate.

1.5.3.4 GTP Solvents.

The solvents used in GTP vary greatly depending on the solubility of the monomer, initiator and catalyst. The most common GTP solvent is THF, even though many other solvents are also suitable.170 Typical solvents for methacrylate polymerisations using a nucleophilic catalyst are toluene, THF, 1,2-dichloroethane, chlorobenzene and N,Ndimethylformamide, n-heptane and various esters (e.g. propylene carbonate).154,171,172 Acrylate polymerisations proceed well in either halogenated alkanes, such as dichloromethane, or aromatic hydrocarbons, such as toluene. The active chain ends in GTP are intrinsically reactive and susceptible to destruction by adventitious impurities. Since the silyl ketene acetal initiators are hydrolytically unstable and sensitive to protic sources. Protic and electron donor solvents are not suitable for GTP. Thus alcohols, most ketones, esters and nitriles cannot be used.173 In general, GTP should be performed under rigorously dry conditions, free from protic sources and other electrophilic agents, and under an inert atmosphere.

1.5.3.5 GTP Mechanism.

Since the introduction of GTP in 1983 the polymerisation mechanism has been widely contested. Two mechanisms, associative and dissociative, have been suggested. The Du Pont group originally proposed an associative pathway as shown in Figure 1.16.

In the associative mechanism propagation proceeds by an intra-molecular Michael addition in the presence of a nucleophilic catalyst. This results in the transfer of a

23


trialkylsilyl group from the initiating species to the carbonyl group of the incoming monomer, hence regenerating the “living” chain end.149 R Si

R

R Nu R Si

R Nu

+

O

R Nu R R

MeO

MeO

Trialkylsilyl initiator

Pentacoordinate silicon

R R

Si

O O

+

O

O

O

MeO

Nu

Si

R

Hexacoordinate silicon

R Nu R Si

R

O O

OMe

MeO

R OMe

MeO

Figure 1.16 The proposed associative mechanism of GTP

For the dissociative mechanism, two possible mechanisms have been advanced174,175: reversible dissociation (see Figure 1.17) and irreversible dissociation with subsequent exchange of trialkylsilyl group (see Figure 1.18).

R

Si

R +

O

OMe

O n

R O-

Nu

+

R3SiNu

OMe Propagation

Ester enolate

MeO Trialkylsilyl initiator

R O O MeO

OMe O MeO H ( CH2

-O

R OMe

R3SiNu

)n

Figure 1.17 The proposed reversible mechanism of GTP

24

O

Si

R

O

OMe +

MeO H ( CH2

)n

Nu


Reversible dissociation involves the reversible reaction of the nucleophilic catalyst with the initiator, which results in the formation of the ester enolate anion and the trimethylsilyl analogue of the catalyst. The enolate species can undergo continual Michael addition to further α,β-unsaturated ester carbonyl species, producing an enolateterminated polymer chain. Finally, the enolate is reversibly resilylated by the NuR3Si species to give a polymeric silyl ketene acetal.

R R

Si

Nu

+

R

Me

O-

Me

OMe

+

O

R3SiNu

OMe

O n

Ester enolate

Propagation Me

Me

MeO Me

O

Trialkylsilyl initiator

O

R R R R O MeO H ( H2C

O

Si ) m Me Me

O

O O

OMe MeO

(

OMe CH 2 ) H n Me Me

Me

Si

R

O

OMe

)m MeO H ( H2C Me

Me Me

MeO

R

OMe

Me

'Dormant' polymer chain

O

O

OMe

MeO H ( H 2C

) n Me

Me

'Living' polymer chain

Figure 1.18 The proposed irreversible mechanism of GTP

In the irreversible dissociation, the enolate formed via desilylation of the trialkylsilyl initiator by catalyst does not undergo resilylation by the NuR3Si species, but rather participates in a rapid reversible complexation reaction with another silyl ketene acetal chain-end functionality, resulting in the formation of a pentacoordinate species176,177. Similarly, the polymer chains are only capable of further chain extension in the free enolate form.

Many studies have been carried out in order to distinguish between these two mechanisms. Evidence in favour of the associative mechanism was reported by Farnham and Sogah,175 who conducted double-labelling experiments and concluded that no silyl

25


group exchange occurred between polymer chain ends: thus the polymerisation apparently proceed via intramolecular transfer of the silyl groups. On the other hand, Quirk and co-workers176-178 proposed a dissociative mechanism which accounted for the experimental observations. Initially, phenyldimethylsilyl ketene acetal initiator was reacted with a living trimethylsilyl-ended PMMA in the presence of catalyst and absence of monomer. After 1 h 80% of the initiator had been incorporated into the living polymer chain. Subsequently, living trimethylsily-ended PMMA and living phenyldimethylsilyl-ended PMMA were mixed in the presence of MMA monomer and catalyst. Chain extension and silyl-ended group exchange was again detected. Under these conditions a dissociative mechanism with ester enolate intermediates is clearly operating. This evidence is more indicative of a classical anionic polymerisation mechanism. Further similarities between GTP and classical anionic polymerisation have been reported by Webster179 and Jenkins.180

1.5.3.6 Termination in GTP

GTP displays the fundamental characteristics of a living polymerisation, including relatively narrow molecular weight distributions, control of molecular weight from the monomer/initiator stoichiometry and the ability to synthesise block copolymers. On the other hand, GTP also suffers from inherent termination reactions, including isomerisation and backbiting, which limit polymer molecular weights to approximately 100,000.

Me

SiMe 3

OMe PMMA

PMMA

OSiMe 3

CO2Me Me

Figure 1.19 Isomerisation of a silyl ketene acetal initiator in the growing MMA chain

end.

Isomerisation: Silyl ketene acetal initiators can isomerise to C-silylated esters which are

unreactive. For example, MTS isomerises to methyl α-(trimethylsilyl)isobutyrate.153

26


Presumably the same reaction occurs with propagating chains (see Figure 1.19). It has been also reported that this isomerisation occurs faster at higher temperatures.181 Thus the discrepancy between the observed molecular weights and the calculated molecular weights are much larger at higher temperature. Nevertheless, O-to-C isomerisation is not a true termination reaction because of its reversibility. CH3O CH3 H

[ CH2

C

]2

O

OSiMe 3

H3C _ Nu

CH2

H3C

CH 3

CO2CH3

CH3 CO2CH3

H3C

+ CH 3OSiMe 3

CO2CH3

Figure 1.20 Backbiting cyclisation of a PMMA trimer.

Another inherent side-reaction in GTP is backbiting, which is represented in Figure 1.20. Termination due to backbiting is not a serious problem for the synthesis of methacrylate homopolymers. It is more problematic in the synthesis of block copolymers and functionalised polymers. In these cases, the polymerisation should not be allowed to reach monomer-starved conditions. In block copolymer synthesis, addition of a second monomer prior to consumption of the first will lead to some tapering of the blocks. Alternatively, if complete polymerisation of the first block is allowed, this will lead to some homopolymer contamination due to premature termination of the chain-ends.

In the synthesis of functionalised polymers, backbiting prior to addition of the terminating reagent will reduce the degree of functionalisation. However, it is possible to minimise this termination reaction by keeping the reaction temperature low and using a bioxyanion catalyst. For example, in a comparison of tetra-n-butyl ammonium bibenzoate (TBABB) and tris(piperidino)sulfonium bifluoride (TPSHF2), the rate of backbiting reaction in the presence of TPSHF2 was 7200 times greater, even when the TBABB concentration was five times greater than that of TPSHF2. Thus both propagation and termination are slower with bibenzoate. Brittain and Dicker also compared the rates of GTP and anionic polymerisation of MMA in THF at 25oC.182 They concluded that the GTP trimer is 30 times more likely to propagate than the anionic trimer, which indicates

27


that the GTP of methacrylates is significantly more ‘living’ than classical anionic polymerisation. The other termination reaction in GTP is chain transfer. Hertler studied the effect of added acids with pKa < 25 (in DMSO) in GTP and found that chain transfer occurred with a significant decrease in molecular weight and often an increase in the polydispersity.183,184 The main use of chain transfer is to reduce the polymer molecular weight to a desired level and to introduce functional end-groups. Some of the more effective transfer agents are the acrylacetonitriles, benzyl cyanide, α-phenylpropionitrile, methylphenyl acetate, indene, fluorene and γ-thiobutyrolactone.185 1.5.4 Atom Transfer Radical Polymerisation (ATRP)

In recent years, atom transfer radical polymerisation (ATRP, see Figure 1.21) has been extensively studied. This new living polymerisation chemistry is applicable to a wide range of monomers, including styrenics,186-189 (meth)acrylates190-192 and acetonitrile.193 ATRP is usually performed either in bulk or in non-aqueous media and is remarkably tolerant of functional groups. The origin of ATRP is based on atom transfer radical addition which has been used successfully in organic reactions.194,195 ATRP has provided a new and efficient way to conduct controlled radical polymerisation.188,189 The ATRP of methacrylates using various alkyl halides as initiators and a catalyst which comprises a transition metal complexed by a bidentate nitrogen-based ligand, e.g. CuX/2,2’bipyridine (bpy), proceeds in a controlled “living” fashion (see Figure 1.21).189,196-198 The resulting polymers can have remarkably narrow polydispersities (Mw/Mn as low as 1.05). The rate of polymerisation depends on the initiator structure/activity, the catalyst activity, solvent polarity, functional groups of the monomers and temperature.199 For example, it increases at higher temperature due to the increased propagation rate constant and the equilibrium constant.

R-X

+

Cu(I)/(bpy)2

.

ka

R

kd

+

kp Monomer

Figure 1.21 Reaction scheme of ATRP. 28

X-Cu(II)/(bpy)2


Block copolymers can be synthesised by two methods using ATRP. The first approach involves addition of a second monomer to the reaction medium after nearly complete consumption of the first monomer. The second method involves the isolation and purification of the first polymer, then using this as a macro initiator.192,200 ABA triblock copolymers can also be prepared via ATRP using bifunctional initiators.201

Unlike ionic polymerisation, ATRP exhibits a tolerance of trace impurities, e.g. no moisture sensitivity and functional group tolerance.

The polymerisation of DMA monomer by ATRP has been investigated by Matyjaszewski et al.

190,202

Various ligands can be used in the system and different factors including

temperature, initiator and solvent can be varied to optimize the reaction.

1.6 MICELLISATION

Block copolymers when dissolved in a selective solvent (i.e. a solvent that is thermodynamically good for one block and poor for the other) arrange themselves into multi-molecular structures called micelles (see Figure 1.22). In dilute solution spherical micelles are formed, with the soluble block forming the solvated corona and the insoluble block located in the micelle core.

There are many experimental techniques available for the study of block copolymer micelles in solution. These include fluorescence spectroscopy, transmission electron spectroscopy, proton NMR spectroscopy, static and dynamic light scattering, small-angle x-ray and neutron scattering and gel permeation chromatography.

UNIMERS

MICELLES

Figure 1.22 Schematic representation of micelle formation by an AB diblock copolymer.

29


Early micellisation studies were of hydrophobic block copolymers in non-aqueous media. Block

copolymers

pyridine)

204

such

as

polystyrene-butadiene,203 204

and polystyrene-hydrogenated isoprene

polystyrene-poly(2-vinyl

were particularly common. For

example, Plestil and Baldrian203 studied the micellisation of polystyrene-butadiene diblocks in both methyl ethyl ketone (a selective solvent for polystyrene) and n-heptane (a selective solvent for polybutadiene, leading to ‘inverse’ micelles). In some cases, these block copolymers are commercially available.206,207 Practical applications of these nonaqueous micellar systems were rather limited, however. With the advent of improved living

polymerisation

techniques,

the

preparation

of

well-defined

hydrophilic/hydrophobic block copolymers became possible and interest shifted towards micelles in aqueous media.

Block copolymers capable of forming micelles in water may be divided into two groups: (1) hydrophilic-hydrophobic block copolymers and (2) hydrophilic-hydrophilic block copolymers. Hydrophilic-hydrophobic block copolymers such as PEO-PBO148,208 and DMA-MMA76,78 form micelles in aqueous media, due to the permanently hydrophobic nature of one of the blocks. However, such block copolymers are usually molecularly dissolved in a non-selective co-solvent prior to the addition of water, which leads to micelle formation.209 Detailed studies of the aqueous solution properties of PS-PMAA210 and PS-PVP83,211 have also been published.

Hydrophilic-hydrophilic block copolymers provide an alternative approach. These copolymers can be dissolved molecularly in aqueous solution and then micellisation can be subsequently induced by selectively reducing the solvency for one of the blocks. For example, Forder et al. synthesised hydrophilic-hydrophilic block copolymers by the anionic polymerisation of methyl vinyl ether (MVE) with either methyl triethylene glycol vinyl ether (MTEGVE)212 or vinyl alcohol (VA).213 Both diblock copolymers were soluble in water at room temperature as unimers but formed micelles when the solution temperature was raised above the cloud point of the MVE block, which became partially hydrated and formed the micelle cores. Variable temperature NMR studies confirmed that micellisation was reversible: on cooling to below the cloud-point the micelles broke up into unimers. The unimer-micelle transition was studied a function of temperature by Nivaggioli et al.214 and Alexandridis et al.215 These workers studied micellisation via the

30


solubilisation of water-insoluble UV-absorbing compounds (1,1’-dipyrenyl methyl ether and 1,6-diphenyl-1,3,5-hexatriene respectively). When dispersed in aqueous solution these compounds do not display their normal UV spectra. However, upon micellisation the hydrophobic probe partitions predominantly into the micelle core and a characteristic shift in the UV spectrum is observed.

1.7 CHARACTERISATION TECHNIQUES 1.7.1 Dynamic Light Scattering158

Dynamic light scattering (DLS, also known as Photon Correlation Spectroscopy) is an experimental technique by which the translational diffusion coefficients of dissolved macromolecules, or dispersed latex particles, may be determined in dilute solution. A laser beam is passed though the solution or dispersion, where it interacts with the ‘particles’ causing the incident light to be scattered. Brownian motion of the particles in solution causes local concentration fluctuations, so the scattered light fluctuates in intensity. The rate of fluctuations depends on the rate of diffusion of the particles: small particles diffuse quickly, large particles more slowly. Experimentally, the photon correlation technique is used, in which the scattered light intensity is collected by a photo-multipler and an intensity correlation function is constructed using an autocorrelator. This function is defined as: G1(τ) = e-τ/T

where T is the relaxation time for diffusion (which is inversely proportional to the translational diffusion coefficient) and τ is the correlation time.74 According to Einstein, the free particle diffusion coefficient (Do) at infinite dilution is:216 Do = kT/ƒo where k is the Boltzmann constant, T is the absolute temperature and ƒo is the friction coefficient at infinite dilution (ƒo is defined as the point at which a sedimenting particle experiences an equal and opposite resistive force from the surrounding medium). ƒo may

31


be expressed in terms of the hydrodynamic shape of a particle using Stoke’s law for a sphere:

ƒo = 6RHηπ

where RH is the hydrodynamic radius of a sphere and η is solvent viscosity. The macromolecule or particle is therefore considered in terms of an equivalent hard sphere radius. Combination of these two equations yields the so-called Stokes-Einstein equation and relates the diffusion coefficient to the hydrodynamic radius: Do = kT/6RHηπ

DLS measures a z-average diffusion coefficient. The z-average is defined as the size corresponding to the initial slope of the log of the correlation function. In effect, it is the average size corresponding to the mean of the intensity distribution for a narrow distribution and therefore a z-average hydrodynamic radius. One potential problem with DLS is its marked bias towards larger particles, leading to broader distributions. This is because the intensity of the scattered light is proportional to the sixth power of the particle diameter, so a particle with twice the diameter will scatter 64 times more light. Because of this, solutions should be rigorously ‘cleaned’ by ultrafiltration or ultracentrifugation to remove dust. The Stokes-Einstein assumes that the solution is infinitely dilute. In reality, free diffusion occurs even at quite high concentrations (~ 1%). In concentrated solutions, diffusion may be hindered by interactions between particles. However, multiple scattering, (where light is scattered by more than one particle before reaching the detector), will often interfere before particle interactions become dominant. Multiple scattering usually results in a reduction in the apparent hydrodynamic particle size.

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42

Chapter 2-Tertiary amine methacrylate (co)polymers

CHAPTER 2

Synthesis and Characterisation of Tertiary Amine Methacrylate Block Copolymers

43


2.1 INTRODUCTION Increasing attention has been given to water-soluble polymers in recent years. Their many industrial applications includ use as stabilisers,1,2 dispersants3 or emulsifiers.4,5 Until a few years ago, most studies of block copolymer micelles were confined to organic solvents.6-10 In recent years, more attention has been paid to the synthesis of watersoluble block copolymers and their aqueous solution properties such as micellisation, cloud-points and surface activity.

Water-soluble block copolymers can be categorised into two groups; the first group is hydrophilic-hydrophobic block copolymers in which the hydrophilic block can be either neutral or polyelectrolytic such as cationic, anionic or betaine. The synthesis and aqueous solution

properties

of

many

hydrophilic-hydrophobic

polystyrene-based

block

copolymers prepared using various hydrophilic comonomers have been studied, including neutral ethylene oxide,11-16 anionic (meth)acrylic acid,17-21 basic vinyl pyridines22-25 and their cationic derivatives26-28 etc. Similarly, studies of hydrophilic-hydrophobic copolymers based on methacrylic monomers such as DMA-alkyl methacrylates have been reported by many researchers.2,29-34 Baines and co-workers have described the synthesis of hydrophilic-hydrophobic water-soluble block copolymers containing hydrophilic DMA as the major component and various alkyl methacrylates as the minor component.29 The effect of both block composition and salt addition on the solubility of these (co)polymers was investigated. Some of these block copolymers were also used as model steric stabilisers for the dispersion polymerisation of styrene in alcoholic media.2 On the other hand, betainisation of DMA residues of DMA-MMA block copolymers has been carried out using 1,3-propane sultone under mild conditions. This derivatised (co)polymer was also used as stabiliser in the emulsion polymerisation of nBuMA monomer in aqueous media.31,32 DMA homopolymer and DMA-based block copolymers have also been synthesised and their use as synthetic vectors for DNA in gene therapy has been suggested by Hennik and co-workers.35

Generally, micellisation of hydrophilic-hydrophobic block copolymers has been studied in water-rich mixtures with water-miscible organic solvents. The polymer has to be

44


dissolved in a non-selective co-solvent prior to addition of water, in order to ensure complete molecular dissolution.30,36 The second group of water-soluble polymers is hydrophilic-hydrophilic diblock copolymers that contain either double neutral blocks (PEO-PPO,37 PVA-PMVE,38 PMVE-PMTEGVE39), or neutral-anionic (PEO-NaMA40), or cationic-neutral blocks (NiPAM-PEG,41 PEO-2-VP,42 DMA-HEMA43), zwitterionic blocks.44,45 These copolymers offer important advantages over hydrophilic-hydrophobic polymers since both blocks dissolve in water. Micellisation is subsequently induced by selectively reducing the solubility of one of the blocks by changing the solution pH, temperature and/or electrolyte concentration.

The most common behaviour of neutral water-soluble polymers is their precipitation from aqueous solution when the solution temperature is increased above the LSTS, or cloud point, of the polymer. For example, homopolymers of EO, NiPAM, DMA, MEMA, OEGMA, MVE, MMAA are water-soluble at room temperature and precipitate from aqueous solution at elevated temperatures. Thus, double hydrophilic block copolymers should be molecularly dissolved at room temperature (without using co-solvent) due to solvation of both blocks. If the cloud points of these two blocks are substantially different then, as the solution temperature is increased, a unimer-micelle transition should occur first as one of the blocks precipitates, followed by macroscopic precipitation when the second block precipitates. Forder et al.38,39 have reported the synthesis of double hydrophilic block copolymers of both poly(methyl vinyl ether- block-methyl triethylene glycol vinyl ether) and poly(methyl vinyl ether-block-vinyl alcohol) by living cationic polymerisation. As the solution temperature was increased above 50oC, the methyl vinyl ether block became partially dehydrated and formed micelle cores. Similarly, block copolymers of ethylene oxide and propylene oxide are completely water-soluble in cold water provided that the propylene oxide block has a low degree of polymerisation.37,46 Both micellisation and gelation behaviour may be observed, depending on the temperature and block composition; such copolymers are widely used both as polymeric surfactants and in drug delivery applications.

Thermosensitive

block

copolymers

comprising

ethylene

oxide

and

N-

isopropylacrylamide were synthesised by both Zhu et al.41 and Topp et al.47,48 Reversible

45


micellisation occurred when the solution temperature was increased above the cloudpoint of the poly(N-isopropylacrylamide) block. It was suggested that this block copolymer may be suitable for certain drug delivery applications.

In addition, neutral-acidic PEO-MAA block copolymers were used in order to modify the crystallisation of calcium carbonate in aqueous media.49,50 Such copolymers also form ‘block ionomer complexes’ when added to cationic polyelectrolytes such as quaternised poly(vinyl pyridine). Poly(ethylene glycol-block-L-lysine) and poly(ethlene glycol-blockα,β-aspartic acid) mixtures exhibit similar micellisation behaviour; these were termed ‘polyion complex micelles’ by A. Harada et al.51,52

The solution pH is critical for the efficient phase separation of basic water-soluble polymers such as poly(vinyl pyridine)s.42 Such polymers are molecularly soluble below a certain critical pH (around pKa) and become insoluble at higher pH due to deprotonation. Use of co-solvents can also be avoided by using pH-dependent block copolymers which, below a certain critical pH, dissolve as unimers and aggregate to form micelles at higher pH.42,53 Martin and co-workers42 have synthesised ethylene oxide-2-vinyl pyridine block copolymers via anionic polymerisation and demonstrated their pH-induced reversible micellisation behaviour. DMA-MAA,32 poly(sodium 4-styrene sulfonate)-sodium-4-vinyl benzoate,45 2-vinyl pyridine-acrylic acid54 and PEO-tertiary amine methacrylate55 block copolymers all show similar pH-induced micellisation behaviour. These micellising block copolymers could serve as a model for a delivery system, where the solute encapsulated in the micelle cores is released as the micelles break apart when they encounter an acidic or basic medium.42 Other hydrophilic-hydrophilic block copolymers, including 4-vinyl pyridine-methacrylic acid,56 methoxyethyl vinyl ether-ethoxyethyl vinyl ether,57 vinyl alcohol-acrylic acid and vinyl alcohol-acryl amide,58,59 have also been synthesised by other groups. Finally, a double hydrophilic copolymer has been synthesised by Yuk et al.60 DMA was block copolymerised with ethyl acrylamide via free radical polymerisation in 1:1 water/ethanol mixture at 75oC and its thermosensitivity was investigated over a range of pH. This copolymer was used in a glucose-sensitive insulin release system.

46


Depending on the monomer class, water-soluble polymers can be synthesised using anionic or cationic polymerisation, free-radical polymerisation or GTP, using many types of monomers such as (meth)acrylates, ethylene oxides and vinyl pyridines. Although classical anionic polymerisation can be used to synthesise methacrylate-based watersoluble polymers,43,61,62 it requires low temperatures and particular care in order to eliminate side reactions.63,64 Over the last decade or so GTP65,66 has become recognised as an excellent method for the synthesis of methacrylate (co)polymers of controlled structure and narrow molecular weight distribution. The living character of GTP also allows the synthesis of (meth)acrylate block copolymers via sequential monomer addition. As far as we are aware, there have been no studies on the synthesis of dibasic water-soluble block copolymers using either GTP or any other synthetic method in the literature.

In the present work a wide range of hydrophilic-hydrophilic dibasic block copolymers based on tertiary amine methacrylates were synthesised via GTP and their aqueous properties were investigated. Thus, DMA was block copolymerised in turn with three other

tertiary

amine

methacrylate

comonomers,

namely,

2-(diethylamino)ethyl

methacrylate (DEA), 2-(diisopropyl-amino)ethyl methacrylate (DPA) and 2-(Nmorpholino)ethyl methacrylate (MEMA). A series of each of these DMA-MEMA, DMADEA and DMA-DPA diblock copolymers was synthesised, with the DMA content varying from 20 to 80 mol % and the molecular weight of the block copolymers ranging from 5,000 g mol-1 to 40,000 g mol-1. DMA, DEA, DPA and MEMA homopolymers were also synthesised. In addition, a series of DEA-MEMA block copolymers was synthesised in order to investigate reverse micellisation behaviour. The aqueous solution behaviour of all of these homopolymers and block copolymers has been assessed using dynamic light scattering, static light scattering, gel permeation chromatography, surface tensiometry, UV spectroscopy and 1H NMR spectroscopy.

47


2.2 POLYMER SYNTHESIS

2.2.1 General

GTP has been used to synthesize homopolymers and block copolymers with narrow molecular weight distribution and well-controlled molecular weight and comonomer composition. All reactions were carried out under dry nitrogen. All chemicals were purchased from Aldrich, unless otherwise stated. All glassware and transfer needles were dried by storing in an oven overnight at 140oC before use. In order to eliminate surface moisture, all glassware was directly assembled from the oven, flamed out under high vacuum (10-4-10-5 torr) and left to cool to room temperature. Nitrogen was passed through both a silica and a P2O5 drying column prior to use. All monomers were passed down a basic alumina column to remove the hydroquinone methyl ether inhibitor.

2.2.2 Materials

Solvent: Tetrahydrofuran (THF; Fisons) was initially dried over sodium wire and refluxed over potassium for 3 days before use. The dried THF was stored over 4 Å molecular sieves at room temperature and transferred into the reaction vessel via cannula. Monomers: DPA (SP2), MEMA (Polysciences Inc.), DMA and DEA were each passed in turn through a basic alumina column, stirred over calcium hydride and 2,2-diphenyl-1picrylhydrazyl hydrate (DPPH) inhibitor (except MEMA) and then stored at below 0 oC. The monomers were each distilled under reduced pressure before transferring into the reaction vessel by cannula under a dry nitrogen atmosphere.

Initiator: 1-Methoxy-1-trimethylsiloxy-2-methyl-1-propane (MTS) was distilled and stored at -5 oC in a graduated schlenk flask under dry nitrogen prior to use.

Catalyst: Tetra-n-butyl ammonium bibenzoate (TBABB) was prepared by the method of Dicker et al.66 and stored under a dry nitrogen atmosphere.

2.2.3 The Synthesis of Tertiary Amine Methacrylate Homopolymers

48


In order to synthesize a homopolymer by group transfer polymerisation (GTP), the solid catalyst (approximately 10 mg, 2 mol % based on initiator) was added from a side arm under a nitrogen purge into a 250 ml three-necked round bottom flask. THF (100-150 ml) was then transferred into the flask via cannula before the addition of MTS (0.10-2.00 ml). This solution was stirred for 15 minutes and then monomer (typically 5-15 ml) was added dropwise by cannula. In the meantime, a contact thermocouple was attached to the side of the reaction vessel to measure the change of temperature during the addition of monomer. It was observed that the reaction temperature increased by 7-16oC. The reaction mixture was stirred until the solution temperature returned to room temperature (approximately 40-60 min). Then a 0.5 ml aliquot of the reaction mixture was extracted via syringe for GPC analysis. The reaction was quenched by adding methanol (2 ml) to get homopolymer and then the solvent was removed by using a rotary evaporator. Finally, the recovered homopolymer was dried in a vacuum oven at 50-60oC for at least 2 days.

2.2.4 The Synthesis of Tertiary Amine Methacrylate Diblock Copolymers.

In order to get an AB diblock copolymer, the 0.5 ml aliquot was extracted from the reaction mixture (as described above) and then the second monomer (depending on the desired block copolymer composition) was added dropwise at an approximate rate of 1 ml min-1 via cannula and a second exotherm was recorded. The reaction mixture was left stirring at room temperature until the exotherm had abated (approximately 60 minutes). After a further 0.5 ml aliquot was extracted for GPC analysis, the block copolymer was terminated with methanol (2 ml) prior to recovery using a rotary evaporator. The resulting polymer was dried in a vacuum oven at 50-60oC for 2 days. Copolymer of differing compositions were produced by changing the molar ratio of comonomers and different molecular weights were obtained by varying the comonomer/initiator ratio. All copolymerisations gave very high yields (> 96%). In all block copolymerisations, the first polymerisation was carried out by using DMA as the first block and followed by the addition of DEA, DPA or MEMA monomer. The same process was followed for the synthesis of DEA-MEMA block copolymer (DEA was polymerised first).

2.3 (CO)POLYMER CHARACTERISATION

49


2.3.1 Gel Permeation Chromatography (THF eluent)

Molecular weights and molecular weight distributions of all (co)polymers were determined by using gel permeation chromatography (GPC). The GPC consisted of a Perkin Elmer LC pump and a RI detector, the columns used was either Mixed ‘E’ or Mixed ‘D’ (Polymer Labs), and calibration was carried out using PMMA standards (Polymer Labs), with Mn ranging from 680 g mol-1 to 53,000 g mol-1. The GPC eluent was HPLC grade THF stabilized with BHT, at a flow rate of 1 mL min-1.

2.3.2 Nuclear Magnetic Resonance Spectroscopy (NMR)

The compositions of all block copolymers and their micellisation behaviour in water were investigated using either a Bruker AC-P 250 MHz instrument or 350 MHz instrument and either CDCl3 or D2O/NaOD or D2O/DCl solvents. The block copolymer compositions were determined by comparing appropriate integrals assigned to the different comonomers.

2.3.3 Turbidimetry

A PC-controlled Perkin Elmer Lambda 2S UV/VIS spectrometer was used to determine not only the effect of homopolymer molecular weight on the cloud points but also the effect of varying the copolymer composition in the DMA-MEMA block copolymers (Mn= 5,000 g mol-1). An aqueous solution of the (co)polymer (2.5 ml, 1 w/v%) was transferred to a 10 mm path length quartz cuvette containing a stir bar. The cuvette was placed in the sample compartment of the instrument and stirring was initiated using a miniature magnetic stirrer. After a small temperature probe was immersed in the upper part of the copolymer solution, the solution temperature was increased slowly from 20 to 65 oC. The optical density at 500 nm and the temperature were monitored simultaneously.

2.3.4 Hydrogen Ion Titration of (Co)polymers

50


The titration of a 0.5 % (co)polymer solution was carried out using 1.0-0.5 M NaOH solution. pH was measured by using a Corning Check-Mite pH sensor. The calibration was carried out using pH 4, 7 and 10 buffers.

2.3.5 Dynamic Light Scattering Studies (DLS) The hydrodynamic size of the block copolymers in aqueous solution was measured using a Malvern PCS 4700 spectrometer equipped with a 80 mV argon ion laser operating at λo = 632.8 nm and a series 7032 Multi-8 Correlator. The measurements were performed at a fixed angle of 90o and data were fitted using both monomodal cumulants analysis and the CONTIN algorithm. All measurements were carried out using 1 w/v% solutions. The solution temperature was controlled to ± 0.1 oC.

2.3.6 Static Light Scattering Studies (SLS) Static Light Scattering (SLS) measurements for the 40:60 DEA-MEMA block copolymer were carried out using a Sofica instrument, equipped with a He-Ne laser (vertically polarised. λ = 633 nm) and a digital voltameter, in the angular range of 30-150o. First, the refractive index increments, dn/dc, of the unimers (in THF) and the micelles in aqueous were determined using a Brice-Phoenix differential refractometer (λ = 633 nm). Before determination of the dn/dc for the micellar solution with MEMA cores in the presence of 1.0 M Na2SO4 and at pH 6.5, the solution was dialysed against 1.0 M Na2SO4 solution (pH 6.5). After determination of the refractive index increments of the solutions, the scattered light of the micellar solutions with both DEA cores at pH 8 and MEMA cores in the presence of 1.0 M salt and pH 6.5 in the concentration range from 0.12% to 0.6%.

2.3.7 Surface Tensiometry The surface tension measurements were carried out using a Kruss K10ST surface tensiometer and platinum ring for both homopolymers and block copolymers by changing either the copolymer concentration or solution pH (the latter was measured using a Corning Check-Mite pH sensor). 2.4 RESULTS AND DISCUSSION

51


2.4.1 Homopolymer Synthesis GTP was used to synthesise a series of each of the DMA, DEA and MEMA homopolymers (see Figure 2.1) for aqueous solubility studies and also as controls for quaternisation and betainisation. The molecular weight of the DMA homopolymers ranged from 1 x 103 to 5 x 104 g mol-1. The molecular weights of both the DEA and the MEMA homopolymers ranged between 1 x 103 and 3 x 104 g mol-1. Only one DPA homopolymer was synthesised; it had a molecular weight of 4,800 g mol-1 (see Table 2.1).

CH3

( CH2

C

)x

C

CH3

CH 3

( CH 2

C C

O

( CH2

)x O

N

N H3C

H 2C

CH3

H 3C

PDMA

CH 2 CH 3

CH 2 H 3C

CH2

H2C

O

CH 2

CH2

H2C

)x

O

CH2

N

C C

CH2

CH 2

CH2

( CH 2

O

O

CH 2

CH2

)x

C

O

O

C

CH 3

C

C H 3C

CH 3

N H H

CH 3

O

PDEA

PMEMA

PDPA

Figure 2.1 Chemical structures of the four tertiary amine methacrylate homopolymers The number-average molecular weights (Mn) and the polydispersities (PD) of the homopolymers were determined by GPC and are summarised in Table 2.1. In general, good agreement was observed between the theoretical and the observed Mn as determined by GPC in THF. All (co)polymers had low PD’s (< 1.20), which is typical of (co)polymers synthesised via GTP.65 The observed increases in Mn compared to theoretical values are almost certainly due to the fact that the hydrodynamic volumes of the tertiary amine methacrylate (co)polymers in THF are different to the PMMA standards. Figure 2.2 shows the

1

H NMR spectra of the four tertiary amine methacrylate

homopolymers, recorded in CDCl3 with the relevant signals labelled.

52


a) PDMA homopolymers: The peak labelled A at δ 4.1 in Figure 2.2a represents the two hydrogens of the methylene group bounded to oxygen, the signal labelled B at δ 2.6 represents the two hydrogens of the methylene group bounded to nitrogen, and the signal labelled C at δ 2.3 represents the six hydrogens of the two methyl groups attached to nitrogen. b) DEA homopolymers: The peak labelled A at δ 4.0 in Figure 2.2b represents the two hydrogens of the methylene group bounded to oxygen, the signals labelled B and C at δ 2.8 and 2.6 represents the six hydrogens of the three methylene groups bound to nitrogen, and the signal labelled D at δ 1.1 represents the six hydrogens of the two methyl groups of the amine residues. Table 2.1 Number-average molecular weights, polydispersities and aqueous solution properties of four tertiary amine methacrylate homopolymers, PDMA, PDEA, PMEMA and PDPA. Sample Code

Homopolymers

Mn (theory) (g mol-1)

Mn (exp.) (g mol-1)a

PD a

Cloud Point (oC)b

Surface Tension (mN/m)c

VB32D VB32C VB81 VB84 VB83 VB32E VB30B VB30A

PDMA PDMA PDMA PDMA PDMA PDMA PDMA PDMA

950 1,150 3,450 5,050 6,320 10,100 15,150 24,650

1,450 1,600 3,350 4,750 6,150 12,450 32,000 53,000

1.16 1.17 1.12 1.14 1.11 1.07 1.04 1.14

46.4 46.6 44.9 43.2 40.7 38.3 34.5 32.2

37.2 39.6 41.8 42.2 42.4 42.7 42.6 42.8

VB35A VB35B VB27 VB35C VB35D VB189

PMEMA PMEMA PMEMA PMEMA PMEMA PMEMA

1,200 2,500 5,350 10,600 21,350 31,000

1,750 2,650 4,950 12,100 24,450 32,000

1.22 1.25 1.10 1.08 1.07 1.13

53.4 49.0 46.2 41.2 36.3 34.0

-------------

VB48 VB50 VB51 VB49 VB52 VB53 VB54

PDEA PDEA PDEA PDEA PDEA PDEA PDEA

3,100 4,200 5,850 9,700 14,000 18,650 24,250

3,550 4,350 5,650 11,000 15,000 21,500 33,700

1.18 1.16 1.11 1.06 1.06 1.06 1.05

insol insol insol insol insol insol insol

---------------

VB77

PDPA

4,200

4,800

1.12

insol

---

a: As determined by GPC (calibrated with poly(methyl methacrylate) standards) b: As determined by turbidimetry. c: As determined by surface tensiometry.

53


CH 3

A) ( CH 2

)x

C C

O

C

O CH 2 A

-CH2-

CH 2 B

A

N

B

CH 3 C

C H 3C

7.0

6.0

B)

-CH3

5.0

4.0

3.0

2.0

1.0

CH 3

( CH 2

)x

C C

O

D

O

C

CH 2 A CH 2 B N C H 2C

CH 2 C

D H3C

CH 3 D

7.0

6.0

5.0

-CH2-

B

A

4.0

3.0

2.0

1.0

2.0

1.0

CH 3

C) ( CH 2

)x

C C

O

D

O

C

CH 2 A CH 2 B

A

B

N CH 2 C

C H2C

CH 2 D

D H 2C O

7.0

6.0

5.0

4.0

3.0

CH 3

D) ( CH2

C

)x

C

D

O

O CH 2 A CH 2 B D

{

H3C H3C

CH 3

N C

C

CH 3

H H

}

-CH2D

A

C

B

C

7.0

6.0

5.0

4.0

3.0

2.0

1.0

δ / ppm Figure 2.2 Typical H NMR (CDCl3) spectra of a) PDMA homopolymer (Mn= 6,150 g mol-1), b) DEA homopolymer (Mn= 5,650 g mol-1), c) MEMA homopolymer (Mn= 32,000 g mol-1) and d) DPA homopolymer (Mn= 4,800 g mol-1). 1

54


c) DPA homopolymers: The peak labelled A at δ 3.9 in Figure 2.2c represents the two hydrogens of the methylene group bounded to oxygen, the signal labelled B at δ 2.7 represents the two hydrogens of the methylene group bound to nitrogen, the signal labelled C at δ 3.1 represents the two tertiary hydrogens of the diisopropyl group bound to nitrogen, and the signal labelled D at δ 1.1 represents the twelve diisopropyl hydrogens of the four methyl groups in the amine residues in Figure 2.2c. d) MEMA homopolymers: The peak labelled A at δ 4.1 in Figure 2.2d represents the two hydrogens of the methylene group bound to the ester oxygen, the signals labelled B and C at δ 2.6 and 2.5 represent the six hydrogens of the three methylene groups surrounding nitrogen, and the signal labelled D at δ 3.7 represents the four -CH2OCH2- hydrogens in the MEMA residues. It is also possible to determine the stereoregularity of these homopolymers from their 1H NMR spectra. It is evident from Figure 2.2 that the resonance of the backbone methylene protons of the four tertiary amine methacrylate homopolymers at δ 1.7-2.0 is broad singlet and so these polymers are predominately syndiotactic.*

2.4.2 Aqueous Solution Properties of the Homopolymers The aqueous solubility of the four tertiary amine methacrylate homopolymers are illustrated in Figure 2.3. The DMA and MEMA homopolymers are both weak polybases which are water-soluble at both neutral and acidic pH at room temperature. However, they precipitate from neutral or basic aqueous solutions at 32-53oC, depending on their molecular weight (see Figure 2.4). When the solution is cooled, the polymer becomes soluble again. This thermoreversibility has been observed by many researchers with different neutral polymers based on methyl vinyl ether, methyl triethylene glycol vinyl ether, isopropylacrylamide, ethylene oxide etc. For example, Folder et al.39 has reported temperature-induced micellisation using MTEGVE-MVE diblock copolymer. In the MTEGVE-MVE system, the differences between cloud points of the related blocks are

* “Spectroscopy of Polymers”, J. L. Koening, ACS Professional Reference Book, Washington, 1992.

55


around 30-40oC. As the solution temperature increases, one block becomes partially dehydrated and forms a micelle core while the other block is still solvated. It was expected that DMA-MEMA block copolymers would show similar behaviour despite the relatively small differences between the cloud points of the two blocks. However, Lowe32 reported that no well-defined micelles were formed: only large aggregates of ~ 650 nm were observed above 40oC. 0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Solution pH

PMEMA PMEMA

In the presence of salt

Such as 1 M M2SO4, M3PO4 etc.

PDMA PDEA PDPA

Soluble

Less soluble

Much less soluble

Insoluble

Figure 2.3 Solubility of the four tertiary amine methacrylate homopolymers in aqueous media at 20oC. In the present work, we focused on the basicity differences between blocks and the effect of varying the solution pH on the cloud points of these blocks. As can be seen in Figure 2.4, the cloud points of DMA and MEMA homopolymers decreased monotonically with increasing degrees of polymerisation (see Table 2.1). This trend was expected since, in the lower limit degree of polymerisation, the DMA and MEMA monomers are watermiscible at all temperatures. For low degrees of polymerisation (Dp < 105), MEMA homopolymers are more soluble than DMA homopolymers. The cloud points of both homopolymers with degrees of polymerisation of around 105-110 are approximately 37oC. Above this Dp, the cloud point of the MEMA homopolymer is lower than the cloud point of the DMA homopolymer. The cloud point of MEMA homopolymer falls from 53.4oC at a degree of polymerisation of ~ 9, to 32oC at a degree of polymerisation of 156. Likewise, for DMA homopolymers, the cloud point varies from 46.4oC for a degree of polymerisation of 9, down to 32.2oC for a degree of polymerisation of 337. Tong et al.67 56


have studied the effect of the polymer concentration on the cloud points of poly(Nisopropylacrylamide) (PNiPAM) using the polymers with the molecular weights of 49,400 (1) and 101,000 (2). They have demonstrated that the cloud point slightly decreased from ~ 33oC to ~ 30.5oC when the polymer concentration is increased up to 55 wt%. The cloud point of (2) is slightly lower than the clout point of (1).

PDMA PMEMA

o

Cloud Point ( C)

50

45

40

35

0

50

100

150

200

250

300

350

Degree of Polymerisation

Figure 2.4 Effect of the chain length on the cloud points for a series of DMA and MEMA homopolymers (no acid-base addition). In addition, MEMA homopolymers are more soluble at high pH (at room temperature) than DMA homopolymers. An increase in the solution pH also slightly decreases the cloud points of both homopolymers. It was also observed that MEMA homopolymer can be precipitated (salted out) relatively easily from aqueous solution on addition of electrolytes such as Na2SO4, K2CO3, Na3PO4 etc. However, MEMA homopolymer can be redissolved as a cationic polyelectrolyte by the addition of acid even in the presence of high salt concentration due to protonation of the morpholine groups.

In contrast, it was observed that the DEA and the DPA homopolymers were both completely insoluble in aqueous media at both neutral and basic pH (Figure 2.3). This is due to the increasing hydrophobicity of the substituents on the tertiary amino nitrogen atom. However, these latter homopolymers both dissolved readily in acidic aqueous

57


solution (pH 3-4) due to protonation of the tertiary amine groups. In addition, it is also observed that the DEA homopolymer becomes more soluble as the solution temperature was lowered to 5oC. The solubility of the four homopolymers in aqueous media is summarised in Figure 2.3.

The surface tension data for 1.0 w/v% DMA homopolymer solutions show that their limiting surface tensions slightly decrease from 43 to 37 mN m-1 as the molecular weight is decreased from 53,000 to 1,450 (see Table 2.1). This decrease is possibly due to chainend effects: the first unit in the polymer chain is MMA derived from the MTS initiator and is relatively hydrophobic. 12 PDM A PM EM A PDEA PDPA

10

pH

8

6

4

2

0 0

5

10

15

20

25

KOH

Figure 2.5 Titration curves of the four tertiary amine methacrylate homopolymers (1.5x10-2 M tertiary amine residues). The titration curves (see Figure 2.5) for PDMA, PDEA, PDPA and PMEMA were obtained by first dissolving these homopolymers (1.5x10-2 M, based on tertiary amine residues) at pH 2 and then monitoring the pH as KOH was gradually added. From titration curves, we obtained pKa values, which are listed in Table 2.2. Table 2.2 pKa values for the four homopolymers.

58


Homopolyme r

pKa

pKa75

pKa70

PDMA PDEA PDPA PMEMA

7.0 7.3 6.3 4.9

6.6 6.9 ---

7.0 ----

The measured pKa of 7.0 for DMA homopolymer agrees well with pKa values reported in the literature.68-70 The stronger basicity of DEA and DPA homopolymers is expected based on the analogous small-molecules.71 For example, the pKa of trimethylamine (see Table 2.3) is 9.74, and the pKa of triethylamine is 10.76. From Table 2.2 the pKa of DEA homopolymer is slightly larger than the pKa of DMA homopolymer as expected, whereas the pKa of the DPA homopolymer is lower than that of DMA homopolymer. The lower basicity of the PDPA is presumably due to the increased steric hindrance at the nitrogen atom compared with PDMA, but for DEA homopolymer basicity wins over steric hindrance. On the other hand, PMEMA has a very low pKa of 4.9. As can be seen in Table 2.3, the small molecule analogue of MEMA is less basic than that of DEA. The same trend was observed in our homopolymer pKa’s. The order is pKa DEA = 7.3 pKa DMA = 7.0 >

pKa DPA = 6.3 > pKa MEMA = 4,9. A lower pKa was obtained for the MEMA

homopolymer. It is presumably due to the nature of the morpholine ring which contains an electronegative oxygen atom.

Most small molecule tertiary amines have pKa values of around 10. Obviously this is not the case for our polymers. Their pKa values are much more lower than 10. Hoogeveen et al.70 studied the titration of DMA monomer and DMA homopolymer and found a pKa of around 7 for the latter, which is excellent agreement with our pKa value. They concluded that the relatively low pKa of PDMA is due to two effects: First, the intrinsic pKa of the tertiary amine group in DMA is 8.4, which is rather lower than expected. This unusually low pKa has been attributed to intra-molecular cyclisation by Pradny and Sevcik, who have suggested that the amine group forms a cyclic structure with the carbonyl group in the side chain, thus lowering the effective basicity of the former (see Figure 2.6).68

59


CH3

[ O δ−

[

]

C

R

O

N R δ+

CH2

CH3

]

C

O

O

H R

H2C

CH2

+ N O CH2

R

Figure 2.6 Cyclisation of a tertiary amine methacrylate homopolymer

The second effect is that the apparent pKa of a functional group in a polymer chain depends on the degree of dissociation. Since the residues are connected, protonation will be hindered by the build-up of charge density along the polymer chain. Therefore, protonation will occur at a lower pH. Table 2.3 pKa values for the analogues of tertiary amine methacrylate homopolymers. CH3

H

N CH3

N CH3

9.74

72

C2H5 C2H5

10.9872 H

C2H5

N

N C2H5 C2H5

10.7672

O

8.3373

CH3 N C2H5 C2H5

10.4372

The pKa values of the block copolymers lie between the pKa’s of the related homopolymers, as expected. The DEA and DPA homopolymers precipitated from aqueous solution when the solution pH exceeded the pKa due to decreasing degree of protonation, and hence increasing hydrophobicity.

In view of these observations, we anticipated that diblock copolymers based on these tertiary amine methacrylates should have interesting behaviour at different pH and/or different temperature. Thus, the DMA monomer was diblock copolymerised in turn with the other three monomers, DPA, MEMA and DEA. In addition, a series of DEA-MEMA block copolymers was also synthesised using the same chemistry. 2.4.3 Tertiary Amine Methacrylate Block Copolymers 60


2.4.3.1 Block Copolymer Synthesis

CH3

( CH2

C

)x O

C

R:

CH3

( CH2

C

)y

H2C

CH2

C

O

H3C

CH3

O

O

CH2

CH2

CH2 N CH3

H3C DMA block

N

CH2 R DEA, DPA or MEMA block

H3C

CH3

N

DPA

C

C H3C

DEA

CH3

H

H

N H2C

CH2

H2C

CH2

MEMA

O

Figure 2.7 General chemical structure of the tertiary amine methacrylate diblock copolymers A series of each of the DMA-DEA, DMA-MEMA, DMA-DPA and DEA-MEMA diblock copolymers (see Figure 2.7) were synthesised using GTP chemistry. Either the comonomer compositions were varied while the overall molecular weight was kept approximately constant, or the Mn was varied while the comonomer composition was kept constant. Polymerisations were carried out by first polymerising DMA monomer, followed by second monomer (DEA, DPA or MEMA). In the case of DEA-MEMA block copolymer syntheses, the DEA monomer was polymerised first. In most cases, there was generally little or no homopolymer contamination. In the occasional case of high contamination, the block copolymers were precipitated from THF into either nhexane (DMA-MEMA and DEA-MEMA due to insolubility of the MEMA) or water at pH > 8 (DMA-DEA and DMA-DPA). Excellent yields (> 98) were obtained in all polymerisations. Copolymer Mn’s and PD’s were determined by GPC and are summarised in Tables 2.4-2.7. In general, good agreement was observed between the theoretical and the GPC values. All copolymers had low PD’s (< 1.20). As far as we are

61


aware, the DMA-DEA, DMA-DPA and DEA-MEMA block copolymers (see Figure 2.7) are the first reported examples of diblock copolymers in which both block components comprise basic residues. Table 2.4 Copolymer compositions, number-average molecular weights and polydispersities of the DMA-DEA block copolymers. DMA in feed (mol %)

DMA contenta (mol %)


Mn (exp.) (g mol-1)b

PD b

VB66 VB61 VB68 VB70 VB69 VB71

80 74 66 49 35 22

78 72 64 49 36 24

10,400 8,950 9,900 10,600 9,850 9,850

12,400 11,350 9,650 9,550 13,600 9500

1.10 1.10 1.12 1.15 1.09 1.10

VB87 VB88 VB89 VB90

80 70 60 50

75 67 61 50

8,200 9,500 11,300 13,800

8,900 11,050 13,700 15,000

1.10 1.10 1.10 1.10

VB75 VB65 VB74 VB120 VB119

80 68 50 50 35

79 67 50 51 34

20,800 18,900 20,700 26,450 20,150

19,150 21,600 18,350 32,600 35,000

1.13 1.09 1.18 1.10 1.05

Sample Code

a: As determined by 1H NMR spectroscopy b: As determined by GPC (calibrated with poly(methyl methacrylate) standards)

Table 2.5 Copolymer compositions, number-average molecular weights and polydispersities of the DMA-DPA block copolymers. Sample Code

VB85 VB80A VB86

DMA content (theory mol %)




PD b

82 72 60

80 72 61

8,150 9,650 12,050

11,500 12,050 15,750

1.10 1.12 1.11

a: As determined by 1H NMR spectroscopy b: As determined by GPC (calibrated with poly(methyl methacrylate) standards)

62


Table 2.6 Copolymer compositions, number-average molecular weights, polydispersities and cloud points of the DMA-MEMA block copolymers. Sample Code

DMA in feed (mol %)




PD b

Cloud point (oC)c

VB28A VB28B VB28C VB28D VB28E

80 65 50 35 20

82 64 48 36 21

4,450 4,950 5,050 5,000 5,100

5,950 5,800 5,100 5,200 6,000

1.10 1.12 1.14 1.11 1.08

40.6 41.7 42.8 43.2 43.6

VB43 VB42 VB36 VB34 VB33B VB190 VB37A VB37

86 81 60 50 50 38 40 34

85 78 59 49 46 40 38 35

35,350 25,900 27,950 34,350 19,200 25,000 17,700 17,700

45,600 29,750 31,100 33,500 25,500 27,600 33,000 36,000

1.13 1.09 1.08 1.14 1.10 1.09 1.17 1.10

32.7 34.7 34.1 32.8 34.8 33.5 32.6 33.0

VB40 VB39 VB41 VB33A VB91 VB92

79 74 67 50 48 37

76 72 65 48 48 38

12,700 16,750 15,450 19,200 13,500 17,800

15,900 16,700 19,200 21,550 14,950 18,850

1.08 1.10 1.10 1.11 1.10 1.07

37.2 36.2 36.3 35.1 37.3 36.2

a: As determined by 1H NMR spectroscopy b: As determined by GPC (calibrated with poly(methyl methacrylate) standards) c: As determined by turbidimetry

Table 2.7 Copolymer compositions, number-average molecular weights and polydispersities of the DEA-MEMA block copolymers. Sample Code

DEA in feed (mol %)

DEA contenta (mol %)



PD b

VB63 VB257 VB256

28 55 45

27 50 40

7,000 17.000 19,100

10,100 25,900 22,000

1.12 1.06 1.05

a) As determined by 1H NMR spectroscopy b) As determined by GPC 2.4.3.2 The Determination of Comonomer Compositions in CDCl3:

63


Comonomer compositions of the tertiary amine methacrylate block copolymers were determined by 1H NMR spectroscopy (see Tables 2.4-2.7) and good agreement with the expected values was observed. Compositions were determined by comparing well-defined peak integrals assigned to the different comonomers. For example, the 1H NMR spectrum in Figure 2.8a represents a DMA-DEA block copolymer (VB65) which has a content of 67 mol % DMA. The ‘C’ peak integral of the six dimethylamino protons in the DMA residues at δ 2.3 was compared to that of -OCH2- protons and/or the six CH3 protons of amine in the DEA residues at δ 1.0 and 4.0. The DMA content was determined to be 67 mol%, which compared well with the theoretical DMA content of 70 mol %. The 1H NMR spectrum in Figure 2.8b represents a DMA-DPA block copolymer (VB86). Its block copolymer composition was determined by comparing the peak integral C due to the DMA residues at δ 2.3 with the twelve methyl protons or two CH protons of the diisopropyl groups in the DPA residues at δ 1.0 or 3.0. The DMA content was determined to be 61 mol%, which compared well with the theoretical DMA content of 60 mol %. The 1H NMR spectrum in Figure 2.8c represents a DMA-MEMA block copolymer (VB190). The peak integral of the DMA residues at δ 2.3 was compared to that of the four -CH2OCH2- protons of the morpholine groups of the MEMA residues at δ 3.7. The DMA content was found to be 40 mol%, which compared well with the theoretical DMA content of 38 mol %.

The comonomer composition of the DEA-MEMA block copolymer (see Figure 2.8d) was determined by comparing the peak integrals of the four -CH2OCH2- protons of the MEMA residues at δ 3.7 with the ester -OCH2- protons of both the MEMA and the DEA residues at δ 4.1. The DEA content was determined to be 40 mol %, which is lower than the theoretical DMA content of 45 mol %. Some evidence for homopolymer contamination was found in the GPC traces. This DEA homopolymer was removed by precipitating the block copolymer into n-hexane. Thus, the DEA content in the block copolymer was slightly lowered than the target composition.

64


CH3 ( CH2

C ) C

CH3 ( CH2

0.67 O

C ) C

O

O

CH2 A

CH2 D

CH2 B

CH2 E

N

C

B +F

N CH3 C

C H3C

7.0

F H2C

CH2 F

G H3C

CH3 G

6.0

C ) C

E

4.0 δ/ppm

0.61 O

C )

2.0

1.0

C

B)

0.39 O

O

CH2 A

CH2 D

CH2 B

C

G

CH2 E

N

{

H3C

G

CH3

H3C

C

CH3

N

}

C

C

G

CH3

H H

A

7.0

6.0

5.0

CH3 C ) C

F

4.0 δ/ppm

3.0

2.0

1.0

CH3

0.40 O

( CH2

C ) C

C)

0.60 O

O

O

CH2 A

CH2 D

CH2 B

CH2 E

CH3 C

F

C G

A+D

N

N C H3C

B+E D

F

( CH2

3.0

CH3 ( CH2

O

H3C C

G

A +D

5.0

CH3 ( CH2

A)

0.33 O

B+E

CH2 F

F H2C

CH2 G

G H2C O

7.0

6.0

5.0

C

) 0.40

C

O

( CH 2

C

) 0.60

C

O

O

O

CH 2 A

CH 2 E

CH 2 B

CH 2 F

N

N

2.0

1.0

D) H A+E

G

D

C F

C H2C

CH 2 C

G H 2C

CH 2 G

H3C

CH 3 D

H H 2C

CH 2 H

D

3.0

CH 3

CH 3

( CH 2

4.0 δ/ppm

B

O

7.0

6 .0

5 .0

4.0 δ/pp m

3 .0

2.0

1 .0

Figure 2.8 Typical 1H NMR (CDCl3) spectra of a) a 67:33 DMA-DEA block copolymer (Mn= 21,600 g mol-1), b) a 61:39 DMA-DPA block copolymer (Mn= 15,750 g mol-1), c) a 40:60 DMA-MEMA block copolymer (Mn= 27,600 g mol-1), and d) a 40:60 DEA-MEMA block copolymer (Mn= 22,000 g mol-1). 2.4.3.3 The Determination of Comonomer Compositions in D2O or D2O/DCl 65


In some cases, the comonomer compositions were also determined using 1H NMR spectra recorded in D2O or D2O/DCl. For example, the peak integral of the six dimethylamino protons in the DMA residues at δ 2.2-2.6 / pH > 8 in D2O or δ 2.9-3.1 / pH 2 in D2O/DCl was compared to that of the six methyl protons (-CH2CH3) and/or two methylene protons (-OCH2-) of the DEA residues at δ 1.3 and 4.3 / in D2O/DCl at pH 2 for the DEA-containing copolymers, or that of the diisopropylamino protons (twelve equivalent methyl protons at δ 1.4 or two tertiary CH protons at δ 3.8 in D2O/DCl at pH 2 for the DPA-containing copolymers, or that of the four -CH2OCH2- protons in the MEMA residues at δ 3.8 in D2O. In the case of DEA-MEMA block copolymer, the comonomer composition was also determined in D2O at pH 6.5 by comparing the peak integrals of the four -CH2OCH2- protons in the MEMA residues at δ 3.8 with the six CH2 protons surrounding N atom in the DEA residues at δ 3.3-3.7. 1H NMR spectroscopy was also used to investigate the micellisation behaviour of the tertiary amine methacrylate block copolymers in D2O by varying the solution pH using NaOD and DCl.

2.4.4 Aqueous Solution Properties of Tertiary Amine Methacrylate Block Copolymers.

Although structurally very similar to DMA, the DEA and DPA monomers are immiscible in water and both DEA and DPA homopolymers are completely insoluble at neutral and basic pH at room temperature. On the other hand, they can be dissolved molecularly in acidic media due to protonation of the tertiary amine residues as weak cationic polyelectrolytes, which are reprecipitated on addition of base. Under the latter conditions, DMA homopolymer remains water-soluble at room temperature. In view of these solubility differences between the respective homopolymers, we felt that both DMADEA and DMA-DPA diblock copolymers should exhibit pH-induced micellisation. These diblock copolymers behave as hydrophilic-hydrophilic blocks in acidic solution and hydrophilic-hydrophobic blocks in basic solution. One of the problems in studying the micellisation behaviour of conventional hydrophilic-hydrophobic block copolymers is that water-miscible co-solvents (THF, alcohols, DMF etc.) are normally required for efficient dissolution in aqueous solution prior to micellisation. Even then, the hydrophobic component usually ensures that the majority of the copolymer chains exist

66


as micellar aggregates rather than as molecularly dissolved chains.29-32 Thus there is little opportunity to study the kinetics of micellisation under true equilibrium conditions. In our micellisation studies, no co-solvent was required. The tertiary amine methacrylate block copolymers reported here were dissolved molecularly in either neutral or acidic water and the solution pH was then increased above the critical micellisation pH of the polymer solution in order to form micelles.

2.4.4.1 DMA-DEA Block Copolymers

pH-induced micellisation pH 8 pH 2

UNIMERS

DMA block

DEA or DPA block

MICELLES

Figure 2.9 Schematic representation of the formation of micelles for both DMA-DEA and DMA-DPA block copolymers It was observed that if the DMA content of the copolymer is greater than approximately 50 mol % the DMA-DEA block copolymers can be dispersed directly into water at around neutral pH to form micelles of between 10 and 60 nm, depending on the block composition. DEA-rich block copolymers (> 55-60 mol%) are insoluble under these conditions. In our micellisation studies, the block copolymers were directly dissolved in aqueous acid as unimers due to protonation of tertiary amine residues of both blocks at pH < 6.5. The solution pH was then increased above the precipitation pH of the DEA blocks using KOH. Under these conditions, it is expected that micellisation should occur, with the hydrophilic DMA block forming the micelle corona and the hydrophobic DEA block forming the micelle core (see Figure 2.9). Thus, DLS studies were carried out on 1% copolymer solutions to determine the hydrodynamic micelle diameter. In addition, 1H NMR spectra were recorded for both the unimer and micellar solutions in order to monitor relative changes in solvation of the residues. DLS Studies: Examination of all DMA-DEA block copolymer solutions (1 %) at pH 2 by DLS confirmed very weak light scattering and unimer sizes. However, adjusting this solution to above the critical micellisation pH (which depends on the comonomer 67


composition) produced much more intense light scattering due to formation of micelles of 20-60 nm diameter with narrow size distributions (see Table 2.8). Micellisation of all DMA-DEA block copolymers occurred between pH 7-9 depending on the comonomer composition and temperature. As can be seen in Table 2.8, the micelle diameters of the 50:50 DMA-DEA blocks increase from 25 nm to 60 nm at around pH 8 with increasing molecular weight. The diameter also increases with increasing DEA content for a given molecular weight (see Table 2.8). This micellisation proved to be completely reversible: the subsequent addition of acid resulted in complete dissolution of the micelles. In addition to pH-induced micellisation, temperature-induced micellisation was also observed at pH 8. Here the DMA-DEA block copolymer solution was cooled to 5oC. Under these conditions the DEA block is hydrated and the copolymer exists as unimers. On warming to 20oC, the DEA block becomes hydrophobic and micellisation occurs.

Table 2.8. A summary of hydrodynamic diameters, polydispersities, solubility and solution conditions of DMA-DEA block copolymers at 20oC. Sample Code



Solution pH

Micelle Diameter (nm)c

PDc

Soluble in water at pH 7

VB66 VB61 VB89 VB70 VB69 VB71

78 72 61 49 36 24

12,400 11,350 13,700 9,550 13,600 9500

9.0 9.0 8.6 8.1 8.2 ~8

17 19 26 25 33 precipt.

0.240 0.090 0.066 0.106 0.082 ------

yes yes yes yes no no

VB75 VB65 VB74 VB120 VB119

79 67 50 51 34

19,150 21,600 18,350 32,600 35,000

9.2 8.7 7.9 8.1 7.5

26 32 34 50 62

0.085 0.095 0.069 0.099 0.074

yes yes yes (slow) yes (very slow) no

VB70 VB90 VB74 VB120

49 50 50 51

9,550 15,000 18,350 32,600

8.1 8.2 7.9 8.1

25 32 34 50

0.106 0.057 0.069 0.099

yes (slow) yes (slow) yes (slow) yes (very slow)

a) b) c) 1 H

As determined by 1H NMR spectroscopy As determined by GPC As determined on 1 w/v% copolymer solutions by PCS. NMR studies: Initially the 50:50 DMA-DEA block copolymer was molecularly

dissolved in DCl-D2O (see Figure 2.10a). On addition of NaOD, the strong signal at δ 1.3 observed in Figure 2.10a due to the six equivalent methyl protons of the DEA residues

68


completely disappears in Figure 2.10b, indicating that this deprotonated block sequence is no longer solvated at pH 7.9. This is strong evidence for the DEA block forming a hydrophobic micellar core, as expected. As the solution was cooled to 5oC, the signal at δ 1.3 due to the six equivalent methyl protons of the DEA. This indicates that the hydrophobic DEA micellar core became hydrated again at low temperature and the micelles no longer exist. pH -induced m icellisation A) pH 2

CH 3

CH 3 ( CH 2

C

C

D

B + E

F

A + D

C )

0.50 O

( CH 2

C ) C

0.50 O

O

O

CH 2 A

CH 2 D

CH 2 B Cl N +

C H 3C

CH 3 C

G

CH 2 E Cl N+

D F H2C

CH 2 F

G H 3C

CH 3 G

CH 3

CH 3

B) pH 7.9

( CH 2

C ) C

C C H 3C

0.50 O

B

4.0

C

0.50 O

O

CH 2 A

CH 2 D

CH 2 B

CH 2 E

N

N CH 3 C

F H 2C

CH 2 F

G H3C

CH 3 G

No G

C) pH 7.9 a nd 5 o C

4.5

C )

O

No E and F A

( CH 2

G

3.5

3.0

2.5

δ/p p m

2.0

1.5

1.0

Figure 2.10 1H NMR (D2O) spectra of a 50:50 DMA-DEA block copolymer (Mn = 15,000 g mol-1); a) at pH 2, b) at pH 7.9,c) at pH 7.9 and at 5oC. Surface Tension Measurements: Preliminary surface tension vs. pH data for the three DMA-DEA block copolymers (containing 78, 72 and 61 mol % DMA) are shown in Figure 2.11a. As the solution pH is increased the block copolymer becomes strongly

69


adsorbed at the air-water interface, thus lowering the surface tension of the solution. Above pH 8 the limiting surface tension of this solution is approximately 32-33 mN m-1 for the block copolymers containing 78 or 72 mol % DMA and 37 mN m-1 for the 61:39 DMA-DEA block copolymer.

75

A)

VB66 (78 mol% DMA) VB61 (72 mol% DMA) VB89 (61 mol% DMA)

Surface Tension (mN/m)

70 65 60 55 50 45 40 35 30 0

2

4

6

8

10

12

pH 75

B)

VB66 (78 mol% DMA) VB61 (72 mol% DMA) VB89 (61 mol% DMA)


70 65 60 55 50 45 40 35 30 0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

-1

Concentration (g ml )

Figure 2.11 Variation of surface tension with (a) solution pH for 0.2 w/v% aqueous solutions of the 78:22, 72:28 and 61:39 DMA-DEA block copolymers (Mn 12,400, 11,350 and 13,700 g mol-1, respectively); (b) surface tension curves for the same three block copolymers as a function of copolymer concentration at pH 8. This is similar to that obtained with small molecule surfactants but relatively low compared to most other synthetic water-soluble block copolymers. For example, Baines et al.29 reported that the limiting surface tension obtained for a 1 % aqueous solution of

70


an DMA-MMA block copolymer of comparable molecular weight was only 46 mN m-1. Similarly a surface tension plateau of ca. 42 mN m-1 was observed by Teyssie and coworkers74 for a sulfonated glycidyl methacrylate-MMA block copolymer with a similar hydrophilic-hydrophobic balance.

It is also possible to identify the so-called critical micelle concentration (CMC) by determining the concentration dependence of the surface tension of a block copolymer. Figure 2.11b shows the surface tension curves of the DMA-DEA block copolymers with three different comonomer compositions. The CMC for a 61:39 DEA-DEA block copolymer is 0.04 w/v%, which is higher than the CMC of the 72:28 or 78:22 DMA containing DMA-DEA block copolymers. The CMC’s of these latter block copolymers are around 0.02 w/v%, which is much lower than the CMC of between 0.05-0.20 reported for the hydrophilic-hydrophobic DMA-MMA diblock copolymer of comparable molecular weight and composition synthesised by Baines et al.29

The details of PDMA and PDEA homopolymers and DMA-DEA block copolymer have been studied in colloboration with A. Gast Group, and the results have also been published in Macromolecules.75

2.4.4.2 DMA-DPA Block Copolymers

In order to characterise the aqueous solution/micellisation behaviour of the DMA-DPA block copolymers, DLS

and 1H NMR spectroscopy studies were performed. All

measurements were carried out at room temperature. First, 1 w/v% solutions of the 61:39, 72:28 and 80:20 DMA-DPA block copolymers were prepared in turn using the same procedure used in the DMA-DEA micellisation studies. Micelles with DPA cores were obtained by careful adjustment of the solution pH. The diblock copolymer dissolved molecularly in dilute HCl at pH 2. Careful addition of KOH to this acidic solution produced a final pH of between 6.7-9.3 depending on the block compositions (see Table 2.9). Under these conditions, the DPA block is substantially deprotonated and therefore

71

Chapter 2-tertiary amine methacrylate (co)polymers

hydrophobic, while the DMA block remains solvated. Thus, micelles comprising DPA cores and DMA coronas are expected, as shown in Figure 2.9. Proton NMR studies confirm this to be the case. The 1H NMR spectra of the 61:39 DMA-DPA block copolymer in D2O at different pH are shown in Figure 2.12. Both blocks are soluble at pH 2 due to protonation of the tertiary amine residues and are therefore visible in spectrum a. As the solution pH was increased to pH 7 by the addition of NaOD, the disappearance of the peaks due to the DPA residues at δ 1.4 and δ 3.8 in spectrum b indicates the dehydration and reduced mobility of the DPA block. Comparing Figures 2.12a and 2.12b, it is clear that the signals due to the DMA block at around δ 4.4, 3.2 and 2.7 are still prominent at pH 7. This is strong evidence for the DPA blocks forming the micelle cores and the DMA blocks forming the hydrated corona. Table 2.9 A summary of hydrodynamic diameters, polydispersities, and solubilities for DMA-DPA block copolymers at 20oC. Sample Code



pH


PDc

Soluble at 25oC

VB85 VB80A VB86

80 72 61

11,500 12,050 15,750

9.3 8.0 6.7

18 23 40

0.170 0.116 0.067

yes slow no

a) As determined by 1H NMR spectroscopy b) As determined by GPC c) As determined on 1 w/v% copolymer solutions by PCS.

Dynamic light scattering studies indicated micelles with intensity-average micelle diameters of between 18-40 nm at 20 oC depending on the block composition (see Table 2.9). The diameter increases with increasing DPA content. In addition, the polydispersity of the micelle size distribution becomes narrower as the DPA content increases. In general, PD values of less than 0.10 indicate unimodal near-monodisperse micelles. As can be seen in Table 2.9, the micellisation occurs at lower pH with decreasing DMA content. Addition of acid led to reprotonation of the DPA residues, and unimers were again produced at pH 2-4. In addition, the critical micellisation pH for the DMA-DPA block copolymer is lower than that of a DMA-DEA block copolymer of similar

72


molecular weight and DMA content. This is due to the more hydrophobic character and easy deprotonation, pKa = 6.3, of the DPA residues in the DMA-DPA block copolymer.

It was observed that when the DMA content of the copolymer is greater than approximately 65 mol % these DMA-DPA block copolymers can be dispersed directly into water at around neutral pH to form micelles of between 18-23 nm, depending on the block composition. The 61:39 DMA-DPA block copolymer is insoluble under these conditions but becomes soluble on addition of acid.

p H - in d u c e d m ic e llis a t io n CH 3

A) pH 2.0

( CH 2

C

C

D

A+D

F

C )

B+ E

CH 3 ( CH 2

0.61 O

C ) C

0.39 O

O

O

CH 2 A

CH 2 D

CH 2 B + Cl N

H3C

CH3

C

C

D H 3C

{

G

C H 3C

G

CH 2 E N+ Cl- C

CH 3

}

G

CH 3

H H F

B) pH 7.1

CH3

CH3 ( CH2

C ) C

C

( CH2

0.61 O

C O

CH2 A

CH2 D

N

A

H3C C

B

0.39 O

O

CH2 B

No F

C )

CH3 C

CH2 E

{

H3C

G

H3C

CH3

N C

C H H

}

G

No G

CH3

F

4.5

4.0

3.5

3.0

2.5

δ/ppm

2.0

1.5

1.0

Figure 2.12 1H NMR (D2O) spectra of a 61:39 DMA-DPA block copolymer (Mn = 15,750 g mol-1), a) at pH 2, b) pH 7.1. Note the disappearance of the signals due to the DPA residues at pH 7.1, indicating that this block forms the dehydrated micelle cores.

73


2.4.4.3 DMA-MEMA Block Copolymers Lowe32 had previously demonstrated that both a 77:23 and a 36:64 DMA-MEMA block copolymer did not exhibit temperature-induced micellisation. Instead, as the solution temperature was increased, these DMA-MEMA block copolymers undergo phase separation, forming large aggregates with a z-average diameter of 665 nm directly from the unimer phase, with no intermediate micelle phase. In the present work, we focused on the systematic variation of the solution pH and added salt in order to achieve sufficient discrimination between the DMA and MEMA blocks. In addition, DMA and MEMA homopolymers were studied as reference materials. The cloud point difference between the DMA and MEMA blocks in a block copolymer is around 5-10oC which is apparently too small to allow micelle formation with the less hydrophilic DMA block forming the micelle cores.

Temperature-induced micellisation, 55oC, pH 7-8

Salt-induced micellisation, Salt / 25oC, pH 7-8 - Salt

Cool to 25 oC

MICELLES

UNIMERS at pH 7-8 : DMA block

MICELLES

: MEMA block

Figure 2.13 Schematic representation of the formation of micelles for DMA-MEMA block copolymers (pH~7.5) On the other hand, the differences on basicity between the two blocks should give some opportunity to accentuate solubility differences and hence achieve micelle formation. Protonation of the tertiary amine groups occurs between pH 4-6 for MEMA residues (pKa 4.9) and between pH 6-8 for DMA residues (pKa 7.0) (see Figure 2.5). These differences allow selective protonation of the DMA block at pH > 6. It was observed that a small change in the solution pH 8 to pH 7 increased the cloud point of the DMA homopolymer to above 60-70oC due to partial protonation of the DMA residues. Under these conditions, the MEMA homopolymer remains almost neutral and precipitates at around 40-50oC. Thus, the DMA-MEMA block copolymer was dissolved in water and

74


the solution pH was then adjusted from 8.5 to 7.5 by adding a few drops of HCl. Under these conditions, the DMA block is partially protonated and did not precipitate even at high temperature, whereas the MEMA block remains unprotonated. Thus, as the solution temperature was increased above 40-50oC, the MEMA block should become hydrophobic and form micelle cores, while the hydrophilic DMA block will form the solvated corona as shown in Figure 2.13. Alternatively, micellisation should occur at room temperature by the addition of salt to a solution at pH 7.5. Again, the DMA block would be partially protonated and form solvated corona while the MEMA block will be “salted out” and form the micelle cores. Table 2.10 A summary of hydrodynamic diameters, polydispersities and solution conditions of 1 % DMA-MEMA block copolymer at pH 7.5. Na2SO4 conc. (M)

Temp. (oC)


PDc

19,200

< 0.3

< 40

65 65 65 65

19,200 19,200 19,200 19,200

0.3 0.7 0.7 no salt

60 24 40-60 61

unimer 15 19 20 33

------0.256 0.058 0.047 0.412

VB33A VB33A VB33A

48 48 48

21,550 21,550 21,550

< 0.3 0.3 0.7

24 51 24

unimer 20 20

------0.042 0.073

VB37A VB37A VB37A VB37A

38 38 38 38

33,000 33,000 33,000 33,000

< 0.3 < 0.3 < 0.3 0.7

< 40 42 60 24

unimer 20 21 22

------0.044 0.050 0.054

VB190 VB37A VB37 VB37

40 38 35 35

27,600 33,000 36,000 36,000

no salt no salt no salt no salt

65 65 < 50 60

22 26 unimer 22

0.304 0.188 ------0.092

Sample Code


Mn (g mol-1)b

VB41

65

VB41 VB41 VB41 VB41

a) As determined by 1H NMR spectroscopy b) As determined by GPC c) As determined on 1 w/v% copolymer solutions by PCS. The DLS results are summarised in Table 2.10. There are three ways to get micelles with DMA-MEMA block copolymers: a) at pH 7.5 at high temperature without salt; b) at pH 7.5 and high temperature with low salt concentration (e.g. < 0.2 M Na2SO4); c) at pH 7.5 and high salt concentration (e.g. > 0.5 M Na2SO4) at room temperature. The micelle

75


diameters of the block copolymers are summarised in Table 2.10. Variations in copolymer molecular weight and block composition have relatively small effect on micelle diameter. The micelles formed at high temperature are not very stable and aggregation occurs within 5-20 minutes if the temperature is increased by 2-3oC. However, such micelles are stable and fairly monodisperse (see Table 2.10) at room temperature in the presence of high salt concentration. Proton NMR studies support the hypothesis that the MEMA block forms the micelle cores under these conditions.

Figure 2.14 shows the NMR spectra of a 40:60 DMA-MEMA block copolymer in the absence of salt at pH 8.5 (spectrum a) and at pH 7.5 (spectrum b) and in the presence of 0.7 M Na2SO4 at pH 7.5 (spectrum c). All the peaks due to DMA residues at pH 8.5 (see spectrum a) shifted downfield at pH 7.5 (see spectrum b) due to partial protonation while the positions of the MEMA peaks remain unchanged, since these residues are less easily protonated (much less basic). The peaks from the MEMA residues in spectrum b disappear after addition of salt, spectrum c. This indicates that the MEMA residues are no longer hydrated. As the salt is removed via dialysis or the solution pH is lowered to 2, the micelles dissociate into unimers. Micellisation could be induced after addition of salt and/or an increase in pH (pH ~ 7). Cloud point measurements indicated that the critical micellisation temperatures of the DMA-MEMA block copolymers lie between the cloud points of the relevant homopolymers (Table 2.1).

In summary, a series of DMA-based tertiary amine methacrylate diblock copolymers has been synthesised and their pH-, temperature-, and salt-induced micellisation was investigated. A preliminary accounts has been published in Chem. Commun.76 In addition, various shell cross-linked (SCK) micelles were synthesised for the first time using DMA-MEMA diblock copolymers. This work was published in J. Am. Chem. Soc.77 These new materials have some advantages over the SCK micelles previously reported in the literature such as tunable core hydrophobicity, depending on temperature and/or salt concentration (see Chapter 5).

Salt-induced micellisation 76


A) pH 8.5

CH3 ( CH2

G

C F

B

CH3

C )

0.35 C O

( CH2

C

A+D

0.65 O

O

O

CH2 A

CH2 D

CH2 B

CH2 E N

N

E

C)

H3C

CH3

F H2C

C

C

G H2C

CH2 F CH2 G O

F

B) pH 7.5

G

C

A + D

E B

C) pH 7.5 0.7 M Na2SO4 C

No G A

B

4 .0

3 .0

δ /p p m

2 .0

1 .0

Figure 2.14 1H NMR (D2O) spectra of a 35:65 DMA-MEMA block copolymer at 20oC (Mn = 36,000 g mol-1): a) at pH 8.3; b) at pH 7.5; c) at pH 7.5 in the presence of 0.7 M Na2SO4. 2.4.4.4 DEA-MEMA Block Copolymers

It is well known that diblock copolymers form micelles in solvents which are selective for either the first block or the second block.36,75-81 It is also possible to obtain micelles or reverse (inverted) micelles from the same block copolymer by choosing appropriate selective solvents. For example, styrene-butadiene diblock copolymers can form 77


micelles82 with either polystyrene cores (in n-alkanes) or polybutadiene cores (in DMF or MEK) Similarly, it is well known that small molecule surfactants can form micelles and reverse micelles in aqueous and nonaqueous media, respectively. Prior to our study we were not aware of any literature examples of block copolymers, or, indeed, smallmolecule surfactants, which are capable of forming both micelles (A block in the core) and reverse micelles (B block in core) solely in aqueous media. Herein we describe our results with such diblock copolymers (see Figure 2.15); a preliminary account has already appeared in J. Am. Chem. Soc.83 MEMA homopolymers exhibit inverse temperature solubility behaviour and its pKa is 4.9 as discussed earlier. It is in unprotonated form above pH 6. Its cloud point lies between 34-45oC at neutral solution depending on molecular weight. Compared to most other water-soluble polymers, MEMA homopolymer can be also easily precipitated (salted out) from aqueous solution on addition of electrolytes such as Na2SO4, K2CO3, Na3PO4 etc. DEA homopolymer is insoluble above pH 7 and its pKa value is 7.3, but it can be dissolved molecularly in acidic media as a weak cationic polyelectrolyte (due to protonation of tertiary amine residues). It is reprecipitated in addition of base. Under the latter conditions, MEMA homopolymer remains water-soluble at room temperature. In view of these differences in the aqueous solution properties of the respective homopolymers, we felt that a MEMA-DEA diblock copolymer might form either micelles or reverse micelles, depending on subtle variations in solution pH and/or electrolyte concentration. Thus, three DEA-MEMA block copolymers were synthesised by varying the DEA content from 27 to 50 mol % (see Table 2.7).

1.0 M Na2SO4 pH 6.7 - Salt or pH < 6

No salt / pH 8 MEMA block

DEA block

pH < 7

Figure 2.15 Schematic representation of the formation of micelles and reverse micelles for a DEA-MEMA block copolymer.

78


All three diblock copolymers dissolved molecularly in dilute HCl at pH 4. Careful addition of KOH to these acidic solutions at 20oC produced a final pH of between 7.58.5, depending on the block compositions (see Table 2.11). Under these conditions, the DEA block is substantially deprotonated and therefore hydrophobic, whereas the MEMA block remains solvated (and also deprotonated). Thus, micelles comprising DEA cores and MEMA coronas are expected. Proton NMR studies confirm this to be the case. The 1

H NMR spectrum in Figure 2.16 represents a 40:60 DMA-MEMA block copolymer

(VB256) in both CDCl3 and D2O. Comparing spectrum b and c in Figure 2.15, it is clear that the signals due to the DEA residues at δ 1.3 and δ 3.3 are suppressed (indicating lower mobility and decreased solvation for this block), whereas those signals due to the MEMA block at δ 2.6 and δ 3.7 are still prominent. The comonomer compositions of the DEA-MEMA block copolymers (see Figure 2.16a) were determined by comparing the peak integrals of the four -CH2OCH2- protons of the MEMA residues at δ 3.7 with the ester OCH2 protons of both the MEMA and the DEA residues at δ 4.1. In addition, the same molar ratios were also obtained from Figure 2.16b by comparing the peak integrals of peak H at δ 3.7 and peak D at δ 1.3.

Table 2.11 A summary of hydrodynamic diameters, polydispersities, solution conditions and aggregation numbers of 1 % DEA-MEMA block copolymer solutions at 20oC. Sample Code

DEA contenta (mol %)


pH

VB63 VB63 VB63

27 27 27

10,100 10,100 10,100

VB257 VB257 VB257

50 50 50

VB256 VB256 VB256

40 40 40

Micelle diameter/nmc

Na2SO4 concn. (mol dm-3)

DEA core d/(PD)

MEMA core d/(PD)

BuX). Although Et3N is more basic than Me3N, its reactivity is lower than Me3N. This suggests that steric congestion (of either the tertiary amine residues or the alkyl halides) is more important than the basic strength of the tertiary amine. This observation will be discussed in this chapter in the context of tertiary amine methacrylate homopolymers reacting with 1,3-propane sultone to yield polybetaines. Furthermore, selective betainisation of the DMA residues in DMA-DEA, DMA-MEMA and DMA-DPA diblock copolymers can be achieved under mild conditions. Aqueous solution properties of these materials has been assessed using DLS, surface tensiometry and 1H NMR spectroscopy. These studies confirmed reversible pH- and salt-induced micellisation, with the betainised DMA block forming the micelle corona. A short communication reporting our preliminary results for the selective betainisation of tertiary amine diblock copolymers has been published in J. Mater. Chem.35

91

Chapter 3-Selective betainisation


3.2.1 The Synthesis of Tertiary Amine Methacrylate Homopolymers and Block Copolymers See section 2.2.3 and 2.2.4 for the general method used for the syntheses of the tertiary amine methacrylate homopolymers and block copolymers, respectively. In the latter case, DMA was always polymerised first, followed by the addition of DEA, DPA or MEMA. 3.2.2 Betainisation of the Tertiary Amine Methacrylate Homopolymers The betainisation of all homopolymers was examined in both THF and water by using 1,3-propane sultone. First, 2 grams of one of the homopolymers from each series was dissolved in either THF or water (40 ml) and the betainising reagent was then added to the solution at room temperature. Betainisation of the DMA residues was complete within 1624 h in both THF and water. The resulting betainised DMA homopolymer was insoluble in THF and excess betainising agent was readily removed by either soxhlet extraction with THF or by precipitation in THF from aqueous solution. However, betainisation of the DEA and MEMA homopolymers required longer reaction times and elevated temperature in THF. Only DMA homopolymer could be readily betainised in both solvents at room temperature. The other homopolymers did not react with 1,3-propane sultone in both water and THF at room temperature. On the other hand, the DEA and MEMA reacted with this betainising reagent in refluxing THF for 48-96 h. However, some side reactions were observed under these conditions, such as ring-opening of the morpholine groups of the MEMA residues and purification difficulties with the betainised DEA homopolymers, possibly due to oligomerisation or ring opening polymerisation of the betainising agent.36,37 Furthermore, the DPA homopolymer did not react at all with 1,3-propane sultone even after four days in refluxing THF. Presumably, this much reduced reactivity is due to steric crowding of the tertiary amine residues. 3.2.3 Selective Betainisation of the DMA Residues in the Block Copolymers. Selective betainisation of DMA residues in the DMA-DEA, DMA-DPA and DMAMEMA block copolymers (1-2 g) was carried out in THF using a 10 mol% excess of 1,3propane sultone based on DMA residues at room temperature. The solution was stirred

92


for 2 days and gelation occurred within 10-24 h, depending on the DMA content of the block copolymer. The copolymers were generally purified by soxhlet extraction with THF to remove excess betainising reagent. In the case of betainised DMA-MEMA block copolymer, purification was achieved simply by precipitation into n-hexane. The resulting selectively betainised block copolymer was dried in a vacuum oven at 55oC for at least 2 days. The extent of betainisation was assessed by 1H NMR spectroscopy.


3.3.1 Gel Permeation Chromatography (THF eluent): Molecular weights and molecular weight distributions of precursor block copolymers were determined using GPC (see section 2.3.1 for the experimental set-up and parameters). Molecular weights of the selectively betainised diblock copolymers were calculated assuming 100% betainisation. 3.3.2 Nuclear Magnetic Resonance Spectroscopy (NMR): The compositions of all precursor block copolymers, the degree of betainisation and the micellisation behaviour of the selectively quaternised diblock copolymers in aqueous solution were investigated using either a Bruker AC-P 250 MHz

or 350 MHz instrument in D2O/NaOD and

D2O/DCl. Block copolymer compositions were determined by comparing the integrals assigned to the different comonomers (see sections 2.4.3.2 and section 2.4.3.3).

3.3.3 Turbidimetry: A PC-controlled Perkin Elmer Lambda 2S UV/VIS spectrometer was used to determine the effect of varying both the copolymer compositions and molecular weights of the DMA-MEMA block copolymers on their critical micellisation temperatures. See section 2.3.3 for the experimental conditions.

3.3.4 Dynamic Light Scattering Studies (DLS): The hydrodynamic size of the selectively betainised block copolymers in aqueous solution was measured using dynamic light scattering. See section 2.3.5 for a description of the experimental conditions.

3.3.5 Surface Tensiometry: Surface tension measurements were carried out using a Kruss K10ST surface tensiometer equipped with a platinum ring. Either the copolymer concentration of the selectively betainised block copolymers or the solution pH were

93


varied (the latter was measured using a Corning Check-Mite pH sensor calibrated with pH 4, 7 and/or 10 buffer solutions).

3.4 RESULTS AND DISCUSSION

3.4.1 Betainisation of Tertiary Amine Methacrylate Homopolymers

Near-monodisperse homopolymers of DMA, DEA, DPA and MEMA were readily synthesised by GTP (see Chapter 2). Quantitative derivatisation of these four homopolymers was attempted examined with 1,3 propane sultone in both THF and water (see Figure 3.1). The results are summarised in Table 3.1. Although both the DMA and the MEMA homopolymers are soluble in water, the DEA and DPA homopolymers are insoluble in neutral and basic water but are soluble in acidic media due to protonation of their tertiary amine residues (see Section 2.4.2). Thus, betainisation of the DMA and

CH3 ( CH2 C ) x C O O

CH3 O

CH3 CH2

CH2

N CH3

O THF or H2O

S

+

x

O

25oC

( CH2 C ) x C O O

CH2

CH3 + CH2 N CH3 CH2

DMA homopolymer

1,3 Propanesultone

betainised DMA homopolymer

CH2 CH2 _ SO3

Figure 3.1 Reaction scheme for the betainisation of the DMA homopolymer.

MEMA homopolymers was attempted in both THF and water, but betainisation of the both DEA and DPA homopolymers was only evaluated in THF. Betainisation of the DMA homopolymer was carried out with 1,3-propane sultone in both THF28-30 and aqueous medium at room temperature and betainisation was complete after 24 h. The MEMA homopolymer reacted with the betainising reagent both in water at room temperature and in refluxing THF, but side reactions were observed in both cases. An unexpected product was obtained according to 1H NMR studies (not shown). The

94


disappearance of the three methylene protons bound to nitrogen at δ 2.6 - 2.8 CH 2

,

CH 2

N

CH 2

, the decrease in the peak integral of the -CH2-O-CH2- protons at δ 3.7 and

the appearance of three equal new peaks at δ 3.3, 3.9 and 4.4 confirmed that the morpholine ring was at least partially destroyed during the reaction. Betainisation of the DEA homopolymer was also problematic. Significantly longer reaction times (48-96 h) and elevated temperature were required for any significant degree of betainisation, as judged by the onset of gelation. 1H NMR studies suggested that degree of betainisation of DEA homopolymer is 61 mol% even after 84 h in refluxing THF (see Table 3.1). Purification difficulties of the betainised DEA homopolymer suggested that side reactions, such as polymerisation of the betainising reagent, had occurred. On the other hand, the DPA homopolymer remained completely unbetainised even after four days in refluxing THF. Presumably, this much reduced reactivity is due to steric crowding of the tertiary amine residues.

Table 3.1 Number-average molecular weight, calculated number-average molecular weight, degree of betainisation, observed precipitation (gel) time and reaction conditions for the four betainised tertiary amine methacrylate homopolymers, (DMA, MEMA, DPA and DEA). Betainisation was carried out using 1,3propane sultone. Sample Betainised Precursor Calcd. Reaction Code homopolymer Mn Gellation Condotions (g mol-1) a (g mol-1) b

VB95 VB147

bet-DMA bet-DMA

12,450 4,000

22,000 7,100

THF H2O

Degree of Observed Mn Medium (%)c

100% 100%

Reaction Betain.c

Time

8h soluble

24 h at 25 oC 24 h at 25 oC

d

VB162 VB162 VB102

bet-DEA bet-DEA bet-DEA

VB111 VB111

bet-MEMA bet-MEMA

VB97 VB97

bet-DPA bet-DPA

3,550 3,550 5,650

9,350 9,350 ---

THF THF THF/H2O (1/1)

0% 61% no reaction

--24 h 24 h

48 h at 25 oC 84 h at 65 oC 48 h at 25oC

12,100 12,100

19,500 ---

THF H2O

side reac. 24 h side reac. ---

48 h at 65 oC 48 h at 25oC

-----

THF THF/H2O (2/1)

0 --no --reaction

96 h at 65 oC 48 h at 25oC

4,800 4,800

a: As determined by GPC [calibrated with poly(methyl methacrylate) standards] b: As calculated from GPC results of precursor homopolymers c: As determined by 1H NMR spectroscopy d: Both precursor and betainised DMA homopolymers are soluble in H2O 95


Table 3.2. A summary of attempted betainisation reactions on various tertiary amine methacrylate homopolymers with 1,3-propane sultone. DMA

DEA

DPA

MEMA

THF

100%

with side reaction

no reaction

Morpholine ring destroyed

H 2O

100%

solubility problems

solubility problems

Morpholine ring destroyed

For the betainised DMA homopolymer, the degrees of betainisation (see Table 3.1 and 3.2) were calculated using 1H NMR spectroscopy. Figure 3.2a shows the corresponding 1

H NMR spectrum of the DMA homopolymer in D2O with the relevant signals labelled.

Peak A at δ 4.1-4.2 represents the -OCH2- protons, peak B at δ 2.7 represents the -CH2NR2 protons and peak C at δ 2.3 represents the six dimethylamino protons.

After betainisation of this homopolymer with 1,3-propane sultone in THF (see Figure 3.2b), the peaks A, B and C shifted to δ 4.5, 3.8 and 3.1-3.2, respectively. After betainisation, the new peaks (D, E and F) at 3.6 (D), 2.3 (E) and 3.0 (F) correspond to the propyl sulfonate group (see Figure 3.2b). The absence of any unbetainised DMA protons in (which would appear at δ 2.7) ‘spectrum b’ indicates 100% betainisation, but also a comparing of the peak integrals of C and F indicates 100% betainisation. Thus, betainisation of DMA homopolymer was successfully carried out with 1,3-propane sultone at room temperature within 24 h in THF as reported in the litrature.28-30 On the other hand, first time, betainisation of the DMA homopolymer was also carried out in water at room temperature (see Figure 3.2c, compare with spectrum b). The spectrum c is identical to spectrum b and indicates the degree of betainisation 100%.

The majority of the polybetaine (co)polymers reported in the literature were synthesised via free-radical polymerisation of the betaine monomers.11,16,22 Near-monodisperse DMA based (co)polymers were betainised in THF at room temperature using 1,3-propane sultone for the first time by Lowe et all.28-30 Our observations are in excellent agreement with the quantitative degrees of betainisation of the DMA homopolymers previously reported by Lowe and co-workers.

96


Before betainisation

CH3

A)

C

(CH2

C )x C O O CH2 A CH2 B

B

N

A

5.0

4.5

C H3C

4.0

3.5

2.5

3.0

1.5

2.0

CH3 C

1.0

δ/ppm After betainisation in THF

B) CH3

( CH2

C

C

)x

C CH3

C O

O

CH2 A

CH2 B

F A

5.0

4.5

3.5

2.5

δ/ppm

After betainisation in H2O

97

CH3 C

CH2 D

CH2 F _ SO3

E

3.0

N

CH2 E

B D

4.0

+

2.0

1.5

1.0


C)

THF

5.0

4.0

THF

3.0

2.0

1.0

δ/ppm Figure 3.2. in

1

H NMR spectra (D2O) of DMA homopolymer (VB95), before betainisation (A), after betainisation in THF (B) and after betainisation H2O (C).

In summary, fully betainised DMA homopolymer was obtained with using 1,3-propane sultone in both THF and water at room temperature within 24 h. Under the same mild conditions, the DEA, MEMA and DPA homopolymers underwent little or no reaction in either solvents. These observations suggested that the DMA residues in the DMA-DEA, DMA-MEMA and DMA-DPA block copolymers could be selectively betainised at room temperature in either water or THF by restricting the reaction time to 24 h and by using near-stoichiometric quantities of 1,3-propane sultone (relative to the DMA residues) (see Figure 3.3). This proved to be the case, as is demonstrated in the next section.

3.4.2 Selective Betainisation of the Tertiary Amine Methacrylate Block Copolymers and Subsequent Micellisation Studies.

As mentioned in Chapter 2, micelles of DMA-DEA and DMA-DPA block copolymers precipitated from aqueous media at around pH 7-9 due to the reduced in solubility of the DMA corona with increasing solution pH. As the water solubility of the betainised DMA block is much higher than that of the precursor, micelles formed from the betainised block copolymer should be stable across a much wider pH range with the betainised DMA forming the solvated corona and DEA, DPA or MEMA forming the micelle cores (see Figure 3.4). Thus, selective betainisation of DMA residues in DMA-DEA, DMA-DPA and DMA-MEMA block copolymers was attempted using 1,3-propane sultone (see Figure 3.3).

98


CH3

CH3 ( CH2 C ) x C O

( CH2 C ) y C O

O

O

CH2

CH2

THF or H 2 O

S

+ x

O

25 o C

1,3 Propanesultone

H2 C H3 C

O

CH2

CH2

CH2

CH2

CH3

CH2 CH2

N

N CH 2

H 2C

CH 2

CH 3

H2 C

CH 2

H3 C

N C

C H3 C

H

O

CH 3

H

R

Selectively betainised block copolymer

DPA

MEMA

DEA

CH2 SO3-

CH 3

( CH2 C ) y C O

O

H3C N

CH3

CH3

CH3 ( CH2 C ) x C O

+

R

N

R :

O

CH2

CH2 H3C

O

Figure 3.3 Selective betainisation of DMA residues in tertiary amine methacrylate block copolymers using 1,3-propane sultone under mild conditions. ±

± ± ± ± ±

± ± ± ±

± betainised DMA block

±

±

±

pH-induced micellisation

±

± ±

±

pH > 8

± ± ± ±

pH 2

DEA or DPA block

± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±

Polybetaine MICELLES

UNIMERS

Figure 3.4 Schematic representation of the formation of polybetaine-based micelles from selectively betainised DMA-DEA and DMA-DPA block copolymers

3.4.2.1 Selective Betainisation of DMA Residues in DMA-DEA Block Copolymers.

As mentioned in the previous section, betainisation experiments on the DMA, DEA, DPA and MEMA homopolymers confirmed that only the DMA homopolymer was quantitatively betainised at room temperature in THF within 16-24 h. This suggested that the DMA residues in the DMA-DEA block copolymer could be selectively betainised under the same conditions by restricting the reaction time to 24 h. The degrees of betainisation of the DMA blocks were determined by 1H NMR spectroscopy. Figure 3.5 shows the NMR spectra of a 50:50 DMA-DEA block copolymer before and after betainisation. Both precursor and betainised block copolymers were dissolved in DClD2O, which is a good solvent for both block and all protons are visible in the spectra (see Figure 3.5, spectrum a). The block composition of a 50:50 DMA-DEA precursor was

99


determined by comparing the peak integrals of C (at δ 3.0) with that of peak G (at δ 1.2). After betainisation of the DMA residues, the signal at δ 3.2-3.3 is due to the six dimethylamino protons of the DMA residues, whereas the signal at δ 1.3-1.5 corresponds to the six methyl protons of the diethyl groups of the DEA residues (see Figure 3.5, spectrum b). comparing the peak integrals of peak C and peak G gives the same 50:50 copolymer composition as determined for the original DMA-DEA precursor prior to betainisation. In addition, while the signal due to the six dimethylamino protons, after betainisation, shifted to δ 3.2-3.3 and new signals of the propyl sulfonate group appeared at δ 2.3, 3.0 and 3.6, the signals of the DEA residues remained unchanged. Thus betainisation of the DMA residues is both selective and near-quantitative (> 95 %).

A) Before betainisation

CH3

CH3

C

B+E F A +D

( CH2

C

)0.50

C

O

( CH2

C

)0.50

C

O

G

O

O

CH2 A

CH2 D

D

CH2 B _ Cl N+

H3C C

CH3 C

D

CH2 E _ Cl + N

F H2C

CH2 F

G H3C

CH3 G

a) pH 2

100


B) After betainisation and pH-induced micellisation CH 3

CH 3

(

CH 2

C

C

) 0.50

C

O

( CH 2

F H+E A D

) 0.50

C

O

O

O

CH 2 A

CH 2 D

CH 2 B C H3C

C

+

N

D

CH 3 C

CH 2 E _ N + Cl

G

CH 2 H

F H2C

CH 2 F

CH 2 I

G H 3C

CH 3 G

J

CH 2 J _ SO3

b) pH 2

I

B

No g

4.5

4.0

3.5

3.0

2.5

δ/ppm

2.0

1.5

c) pH 12 1.0

Figure 3.5 1H NMR spectra of a 50:50 DMA-DEA block copolymer (VB127): a) before betainisation (DCl/D2O, pH 2). After betainisation; b) betainised DMA-DEA copolymer dissolved in DCl/D2O at pH 2, c) micellar solution of the same betaine block copolymer achieved by adjusting the solution pH with NaOD to pH 12. Figure 3.5 also shows the NMR spectra of the betainised DMA-DEA block copolymer in both acidic and alkaline media. As reported in Chapter 2, the DMA-DEA and DMA-DPA block copolymers exhibited highly pH-dependent surface activity and micellisation. It was suggested that the more hydrophobic DEA (or DPA) block adsorbed at the air-water interface and also formed the interior of the copolymer micelles. This NMR study of the betainised 50:50 DMA-DEA block copolymer now support this hypothesis. Initially, this copolymer was molecularly dissolved in DCl-D2O (see Figure 3.5, spectrum b). On addition of excess NaOD, the strong signal at δ 1.4-1.5 observed in ‘spectrum b’ due to the six methyl protons of the diethylamino groups in the DEA residues completely disappears (see Figure 3.5, spectrum c), indicating that this deprotonated block sequence is no longer solvated. This is strong evidence for the DEA block forming a hydrophobic micellar core, as expected. It is noteworthy that the formation of stable micelles reported in Chapter 2 for the DMA-DEA and DMA-DPA precursor blocks only occurs over a

101


rather narrow pH range; precipitation occurs above pH 8-9 due to deprotonation of the hydrophilic DMA residues. In contrast, since the betainised DMA residues remain soluble in alkaline media, the betainised block copolymer micelles remain in solution up to pH 12-13. Table 3.3 A summary of copolymer compositions, molecular weights, polydispersities (PD) and micelle diameters of various selectively betainised DMA-DEA and DMA-DPA block copolymers. Sample code

Selectively Betainised Block copolymer

DMA Precursor Contenta Mn (mol %) (g mol-1) b

Betainised Mn (g mol-1)c

pH

Temp. (oC)

Micelle Diameter (nm)d

103 116 118 100 124 125 127

Bet-DMA-DEA Bet-DMA-DEA Bet- DMA-DEA Bet- DMA-DEA Bet- DMA-DEA Bet- DMA-DEA Bet- DMA-DEA

78 67 61 49 50 51 36

12,400 11,070 13,700 9,550 18,350 32,600 12,000

19,600 16,500 19,700 12,850 25,000 44,000 15,000

12.0 12.0 11.5 11.0 12.0 12.0 11.0

23 23 20 20 20 20 24

4 20 24 22 29 37 22

107 101 105

Bet-DMA-DPA Bet-DMA-DPA Bet-DMA-DPA

80 72 61

11,550 12,050 15,750

18,250 18,100 22,400

11.0 11.0 11.0

20 20 20

21 22 22

a: As determined by 1H NMR spectroscopy b: As determined by GPC (calibrated with poly(methyl methacrylate) standards) c: As calculated from GPC analyses of precursor polymers (assuming 100% betainisation of the DMA residues) d: As determined by PCS on 1.0 % aqueous solutions

Dynamic light scattering studies of pH-induced micellisation were carried out on dilute aqueous solutions of the betainised block copolymers. Micelle diameters depend on both the copolymer molecular weights and the comonomer compositions of the selectively betainised block copolymers. When the DMA content of the DMA-DEA block copolymer is higher than 80 mol%, micellisation is not possible. Unimer state exists even pH > 8. On the other hand, If the DMA content lower than 30 mol %, macroscopic precipitation occurs when the solution pH is increased over pH 7 without micellisation (see Chapter 2). Thus, for betainised DMA-DEA copolymer micelles, the DMA content should be lower than 80%. As the overall molecular weight was kept constant, the hydrodynamic diameter of the betainised DMA-DEA copolymer micelles slightly increased from 20 nm to 24 nm with increasing DEA content (see entries VB103, VB116 and VB118 in Table 3.3). At constant comonomer composition, the hydrodynamic diameters dramatically increased from 22 nm to 37 nm with increasing copolymer molecular weight (see entries VB100,

102


VB124 and VB125 in Table 3.3). The betainised DMA-DEA block copolymer micelles had reasonably narrow size distributions. Addition of acid caused complete dissociation of the betainised DMA-DEA block copolymer micelles.

The surface activity of the DMA-DEA block copolymer has a strong pH and concentration dependence, as reported in Chapter 2. At high pH, the block copolymer becomes significantly more surface active (the limiting surface tension is ca. 32-34 mN m-1). Presumably, the deprotonated hydrophobic DEA block becomes adsorbed strongly at the air-water interface, thus lowering the surface tension of the solution. Betainisation significantly reduces the surface activities of the copolymers. For example, the limiting surface tension at pH 10-12 for a 1% selectively betainised 78:22 DMA-DEA block copolymer solution is only ca. 51 mN m-1 at pH > 8, whereas the precursor block is much more surface active, exhibiting a limiting surface tension as low as 32 mN m-1 (see Figure 3.6a). This is presumably due to the increased water-solubility of the DMA block with betainisation, which decreases the adsorption of the block copolymer at the air-water interface. The CMC of the 72:28 DMA-DEA block copolymer is around 0.02 w/v%, as estimated from the surface tension vs copolymer concentration curve (see Figure 3.6b). After selective betainisation of the DMA residues, the limiting surface tension vs concentration of this copolymer decreased appreciably to 50-52 mN m-1 (see Figure 3.6b), indicating reduced adsorption at the air-water interface. In addition, the CMC of the betainised DMA-DEA block copolymer is around 0.04 w/v%, which is significantly higher than the CMC of the precursor block copolymer. Clearly, betainisation of these copolymers decreases their surface activity.

103


70

A) Surface Tension (mN/m)

65

AFTER BETAINISATION cmc = 0.044 (w/v%) AFTER BETAINISATION

60 55 50 45 40

BEFORE BEFORE BETAINISATION BETAINISATION cmc = 0.02 (w/v%)

35 30 0

2

4

6

8

10

12

14

pH

80

B)


70

AFTER BETAIN ISATIO N cm c = 0.044 (w /v% )

60

50 BEFO R E BETAIN ISATIO N cm c = 0.02 (w /v% ) 40

30 0,0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

Polym er concentration (w /v% )

Figure 3.6 Variation of surface tension with (a) pH for a 0.2 w/v% aqueous solution of 78:22 DMA:DEA block copolymer (Mn = 12,400 g mol-1); (b) as a function of copolymer concentration at pH 8.5. Betainisation of the DMA residues dramatically reduces surface activity of the DMA-DEA block copolymer. 3.4.2.2 Selective Betainisation of DMA Residues in DMA-DPA Block Copolymers. 104


Again, the degrees of betainisation of the DMA blocks were determined by 1H NMR spectroscopy. Figure 3.7a shows the NMR spectrum of a 61:39 DMA-DPA block copolymer dissolved in DCl-D2O, which is a good solvent for both block sequences. The signal at δ 3.0 is due to the six dimethylamino protons of the DMA residues, whereas the signal at δ 1.4-1.5 corresponds to the twelve protons of the four equivalent methyl groups in each of the DPA residues. Comparing these peak integrals gives a 61:39 DMA:DPA copolymer composition. Figure 3.7b shows the NMR spectra of the betainised DMA-DPA block copolymer in D2O in both acidic and alkaline media. After betainisation of the DMA residues, the signal due to the six dimethylamino protons shifted to δ 3.2-3.3 and new signals of the propyl sulfonate group appeared at δ 2.3, 3.0 and 3.6. The signals due to the DPA residues remained unchanged. Comparing the peak integrals of peak C and peak G gives the same 61:39 copolymer composition as that determined for the original DMA-DPA precursor block prior to betainisation. Thus betainisation of the DMA residues is again both selective and near-quantitative.

In Chapter 2, DMA-DPA block copolymers were shown to exhibit highly pH-dependent micellisation. It was suggested that the more hydrophobic DPA (or DEA) block adsorbed at the air-water interface and also formed the interior of the copolymer micelles. Our NMR studies of the betainised 61:39 DMA-DPA block copolymer now support this hypothesis.

Initially, this copolymer was molecularly dissolved in DCl/D2O (see Figure 3.7, spectrum b). On addition of excess NaOD, the strong signal at δ 1.3-1.4 observed in ‘spectrum b’ due to the twelve equivalent methyl protons of the DPA residues completely disappears (see Figure 3.7, spectrum c), indicating that this deprotonated block sequence is no longer solvated. This is strong evidence for the DPA block forming a hydrophobic micellar core, as expected. Similar spectral changes are observed in the NMR spectrum of the betainised DMA-DEA block copolymer under similar conditions as reported earlier (see Section 3.3.2.1). It is noteworthy that the micellisation behaviour reported in Chapter 2 for the DMA-DEA and DMA-DPA precursor blocks only occur over a rather narrow pH range, since precipitation occurs above pH 8-9 due to deprotonation of the hydrophilic DMA

105


residues. In contrast, since the betainised DMA residues are soluble in alkaline media the betainised block remain in solution as micelles up to pH 12-13. Before betainisation

CH3

CH3

(

CH2

C

C

)0.61

C

O

( CH2

) 0.39

C

O

O

O

CH2 A

CH2 D

CH2 B C H3C

C

+ N

CH2 E _ Cl CH3 N+ C C CH3 H H D

CH3 C G

CH2 H

G

{

H3C H3C

}

G

CH2 I F

A+D

CH2 J _ SO3

B+E

a) pH 2

F

After betainisation and pH-induced micellisation CH3

CH3

( CH2

C

( CH2

) 0.61

C

O

C

) 0.39

C

O

O

O

CH2 A

CH2 D

CH2 B + C H3C N CH3 C G CH2 H

{

CH2 E _ Cl CH3 N+

C

C

H3C H3C

G

D

H

H

}

G

CH3

CH2 I F CH2 J _ SO3

J C

b) pH 2

B+F A+D

E+H

I

no g

4 .5

4 .0

3 .5

3 .0

2 .5

2 .0

1 .5

c) pH 12

1 .0

δ/p p m

Figure 3.7 1H NMR spectra of a 61:39 DMA-DPA block copolymer (VB86): a) before betainisation (DCl/D2O, pH 2), b) betainised DMA-DPA copolymer dissolved in DCl/D2O at pH 2, c) micellar solution of the same betaine block copolymer achieved by adjusting the solution pH with NaOD to pH 12. 106


Dynamic light scattering studies of pH-induced micellisation were carried out on dilute aqueous solutions of the betainised block copolymers. The betainised DMA-DPA block copolymers formed micelles of ca. 22 nm (see Table 3.3) with reasonably narrow size distributions. The comonomer composition did not affect the hydrodynamic diameter of the micelles, but broaden PD was obtained by decreasing molecular weight of the copolymer. Addition of acid caused complete dissociation of the betainised DMA-DPA block copolymer micelles. This micellisation is completely reversible.

3.4.2.3 Selective Betainisation of DMA Residues in DMA-MEMA Block Copolymers.

Both DMA and MEMA homopolymers exhibit inverse temperature solubility behaviour. Their cloud points lie between 32-53oC for 1% aqueous solutions, depending on molecular weight (see Chapter 2). Compared to DMA and most other water-soluble polymers, MEMA homopolymer can be easily precipitated (salted out) from aqueous solution on addition of electrolytes such as Na2SO4, K2CO3, Na3PO4 etc. Normally, it was expected that their block copolymers should have induced micellisation in aqueous media when the solution temperatures are increased above the cloud point of DMA block. This was studied by both varying DMA content from 10 to 90 mol% and molecular weights from 5000 to 50000 g mol-1 and no micellisation was observed as discussed in Chapter 2. Instead of micellisation, the copolymers gave aggregation with the cloud points laying between the clound points of the DMA and MEMA blocks. Similar aggregation with the diameter of around 650 nm was reported by A. B. Lowe but no micellisation was observed.30 Thus, it is difficult to get DMA-MEMA block copolymer micelles with DMA block forming the micelle core due to the small temperature difference (5-10 oC) between the cloud points of these two blocks (see Table 9 and discussion in Chapter 2). As mentioned in Section 2.4.4.3, partial protonation of the DMA residues at pH 7 allows us to obtain stable micelles by increasing the solution temperature or by adding salt at room temperature, with the MEMA block forming the micelle core. However, in both cases while the salt-induced micelles are stable, the micelles obtained at pH 7.5 in the absence of salt by increasing temperature above the cloud point of the MEMA residues are stable only over a rather narrow temperature range (65-68oC) for VB37A.

107


Table 3.4 A summary of copolymer compositions, molecular weights, polydispersities (PD) and micelle diameters of selectively betainised DMA-MEMA block copolymers. Sample Code

DMA Contenta (mol %)

VB109 VB122 VB112 VB121 VB197 VB197 VB197 VB197 VB197 VB197 VB197 VB113 VB113 VB114C VB123

Precursor Mn (g mol-1) b

65 59 48 46 40 40 40 40 40 40 40 37 37 36 35

Calculated Mn (g mol-1)c

19,200 31,150 15,000 25,500 27,600 27,600 27,600 27,600 27,600 27,600 27,600 18,850 18,850 5,200 36,000

29,000 44,000 19,850 33,450 35,000 35,000 35,000 35,000 35,000 35,000 35,000 23,500 23,500 6,450 44,000

Temp. (oC)

Salt Conc. (mol dm-3)

Micelle Diameter (nm)d

21 21 21 21 23 65 25 65 25 65 24 22 21 20 21

1.0 M Na2SO4 0.7 M Na2SO4 0.9 M Na2SO4 0.7 M Na2SO4 no salt / pH 7 no salt / pH 7 pH > 11 pH > 11 0.1 M Na2SO4 0.1 M Na2SO4 0.4 M Na2SO4 0.6 M K2CO3 0.7 M Na2SO4 0.8 M Na2SO4 0.5 M Na2SO4

29 37 26 35 unimer 13 unimer 37 unimer 38 37 33 30 10 46

a: As determined by 1H NMR spectroscopy b: As determined by GPC (calibrated with poly(methyl methacrylate) standards) c: As calculated from GPC analyses of precursor polymers d: As determined by PCS on 1.0 % copolymer solutions

Salt-induced micellisation ±

±

± ± ± ± ±

±

±

Na 2 SO 4 (> 0.2-0.3 M), pH > 7 ±

± ± ± ± ± ± ± ± ± ± ±

± betainised DMA block

MEMA block

-Na 2 SO 4 (< 0.2 M) temperature-induced micellisation (60 o C) pH 10 Cool to 25 o C

UNIMERS

Figure 3.8 betainised

±

± ± ±

±

±

± ±

± ± ± ± ± ± ±

±

±

± ± ± ±

±

MICELLES

Schematic representation of the formation of micelles for selectively DMA-MEMA block copolymers

In order to produce much greater solubility differences between the DMA block and the MEMA block, selective betainisation or quaternisation can be used. Thus stable micelles are formed with the more soluble betainised DMA block forming the solvated corona and

108


the MEMA block forming the micelle core, both at higher temperatures and also at room temperature in the presence of high salt concentrations (see Figure 3.8).

Before betainisation C

CH3

CH3

( CH2 C ) 0.46 C O

G E B F

C)

( CH2

0.54 C O

O

O

CH2 A

CH2 D

CH2 B

CH2 E N

N H3C

CH3

F H2C

C

C

G H2C

A+D

CH2 F CH2 G O

a) After betainisation and pH-induced micellisation CH 3

CH 3

(

B+G

CH 2

C

C

) 0.46

C

O

J

4.5

N o F or E

4.0

3.5

C

O

O

CH 2 A

CH 2 D

CH 2 B

CH 2 E

+

N

N

CH 3 C

CH 2 H

F H2C

CH 2 I

G H 2C

CH 2 F CH 2 G O

I

D

No D

0

) 0.54

CH 2 J _ SO3

E

H A

C

O

F C H 3C

( CH2

3.0

2.5

δ/ppm

w ithout salt

b)

0.5 M K 2 C O 3

c)

2.0 .

1.5

1.0

Figure 3.9 1H NMR spectra (in D2O) of: a) a 46:54 DMA-MEMA precursor block copolymer (VB33B), After selective betainisation of the DMA block (VB121); b) in the absence of salt and (c) in the presence of K2CO3 (0.5 M). Therefore, selective betainisation of the DMA residues of the DMA-MEMA block copolymers was carried out by reacting with 1,3-propane sultone (10% excess based on DMA residues) in THF at room temperature within 24 h. Figure 3.9 shows the spectra of

109


a 46:54 DMA-MEMA precursor copolymer (spectrum a) and after its selective betainisation (spectrum b: in the absence of salt, spectrum c: in the presence of salt, 0.5 M K2CO3). The degrees of betainisation (see Table 3.4) were determined using 1H NMR spectroscopy (see Figure 3.9a). The peak integral of the six dimethylamino protons of betainised DMA residues at δ 3.2-3.3 was compared to that of the six protons of the -CH2groups (at δ 2.5-2.7) bound to the nitrogen of the MEMA residues (see Figure 3.9b). After addition of salt, all peaks due to the MEMA residues completely disappeared (see Figure 3.9c), thus the MEMA block is no longer solvated. Presumably, it forms the non-solvated micelle core, while the betainised DMA block forms the solvated micelle corona. As salt is removed by dialysis, the MEMA residues becomes rehydrated again. Thus, the micellisation is completely reversible. In addition, when the solution temperature (without salt and at pH>8) is increased above the cloud point of the MEMA block, the MEMA block became partially dehydrated and formed the micelle cores while the betainised DMA remained still solvated and formed the micelle corona.

PCS studies confirmed that the diameters of micelles obtained in the presence of salt at 20oC increased from 10 nm to 46 nm with increasing copolymer molecular weight (see VB114C, VB113 and VB125 in Table 3.4: note that the copolymer compositions are similar). In addition, the micelle diameters were between 13-38 nm at high pH, depending on both solution pH and the salt concentration (see VB197 in Table 3.4).

3.5 CONCLUSIONS

We described for the first time that the selective betainisation of the DMA residues in the tertiary amine methacrylate based dibasic block copolymers can be achieved using 1,3propane sultone under mild conditions. Preliminary experiments on the DMA, MEMA, DEA and DPA homopolymers confirmed that only DMA homopolymer was quantitatively betainised at room temperature in THF within 24 h. The betainisation of DMA homopolymer was also successfully carried out in water within 24 h. The DEA and MEMA homopolymers required significantly longer reaction times and refluxing THF. The sterically hindered DPA homopolymer remained completely unbetainised even after four days in refluxing THF. This reactivity differences due to steric hindrance allowed us to study selective betainisation of the DMA residues in the tertiary amine methacrylate

110


copolymers. We have shown that selective betainisation of the DMA residues in the DMA-DEA, DMA-DPA and DMA-MEMA block copolymers can be achieved by reacting with near-stoichiometric amount of 1,3-propane sultone in THF at room temperature. These selectively betainised tertiary amine methacrylate (co)polymers were water-soluble at room temperature both in acidic media and also at neutral pH. Both betainised DMA-DEA and DMA-DPA block copolymers behave as hydrophilichydrophilic blocks in acidic media but as hydrophilic-hydrophobic blocks in neutral and alkali media. Dynamic light scattering and 1H NMR studies confirmed reversible pHinduced micellisation up to pH 13 without any precipitation, with the hydrophobic block (DEA or DPA) forming the micelle core and the hydrophilic block (betainised DMA) forming the solvated corona. The micelle diameters were in the range of 20-40 nm depending on Mn’s and block compositions. Micellisation occurs at around pH 7. In contrast, the precursor blocks precipitate above pH 10 due to deprotonation of the DMA block. In addition, betainisation of the DMA residues in DMA-DEA block copolymer significantly reduces the surface activity of the DMA-DEA copolymer due to the high charge density on the betaine block, which presents efficient packing at the air-water interface.

Selective betainisation of the DMA residues of the DMA-MEMA block copolymers enhanced the solubility difference between these two hydrophilic blocks. Thus stable micelles were obtained, with the MEMA block forming dehydrated micelle cores either at high temperature in alkaline media (pH 7-13) or in the presence of salt at room temperature. In both cases, micellisation was reversible and micelle diameters were in the range of 10-46 nm depending on the solution pH, electrolyte concentration, temperature, block composition and copolymer molecular weight.

In summary, selectively betainised block copolymers exhibited reversible pH-, salt- and temperature-induced micellisation under various conditions with the micelle diameters of 10-46 nm. In some cases near-monodisperse micelles were obtained. Betainisation significantly reduced the surface activities of the DMA-DEA precursor block copolymers.

111


3.6 REFERENCES 1.

a) K. Nagai, Trends Polym. Sci., 4(4), 122, 1996. b) K. Nagai, Macromol. Symp., 84, 29,1994.

2.

a) K. Nagai and Y. Ohishi, J. Polym. Sci.: Part A: Polym. Chem., 32, 445, 1994. b) K. Nagai and Y. Ohishi, J. Polym. Sci.:Part A: Polym. Chem., 25, 1, 1987.

3.

a) K. Nagai, I. Fujii and N. Kuramoto, Polymer, 33(14), 3060, 1992. b) K. Nagai, Y. Ohishi, K. Ishiyama and N. Kuramoto, J. Appl. Polym. Sci., 38, 2183, 1989. c) K. Nagai, Y. Ohishi, H. Inaba and S. Kudo, J. Polym. Sci. : Polym. Chem. Add., 23, 1221, 1985.

4.

D. J. Liaw, S.J. Shiau and K. R. Lee, J. Appl. Polym. Sci., 45, 61, 1992.

5.


6.

J. W. Cleary, Chem. Abstract., 82, 32364f, 1975.

7.

K. Hayama and I. Ito, Chem. Abstract., 85, 11799u, 1976.

8.

T. Ohashi, S. Fujii and K. Kozuka, Chem. Abstr., 85, 5201f, 1976.

9.

M. S. Pusey, Chem. Abstr., 81, 106899n, 1974.

10. H. Ladenheim and H. Morawetz, J. polym. Sci., 26, 251, 1957. 11. R. Hart and D. Timmerman, J. Polym. Sci., 28, 118, 638, 1958. 12. A. Pinazo, M. R. Infante, C. H. Chang and E. I. Franses, Colloids Surf. A, 87, 117, 1994. 13. Y. Chevalier, F. Melis, J. P. Dalbiez and J. Phys. Chem. 96, 8614, 1992. 14. A. Bhatia, S. Qutubuddin, Colloids Surf., 69, 277, 1993. 15. R. H. Ottewill, A. R. Rennie, R. G. Laughlin, and G. M. Bunke, Langmuir, 10, 3493, 1994. 16. V. M. Monroy-Soto and J. C. Galin, Polymer, 25, 121, 1984. 17. V. M. Monroy Soto and J. C. Galin, Polymer, 25, 254, 1984. 18. N. Bonte and A. Laschewsky, Polymer, 37(10), 2011, 1996. 19. J. Cardoso and O. Manero, J. Polym. Sci. Part B: Polym. Physics, 29, 639, 1991. 20. V. Barboiu, E. Streba, C. Luca and C. I. Simionescu, J. Poly. Sci.: Part A: Polym. Chem., 33, 389, 1995. 21. J. S. Salamone, W. Volksen, A. P. Olsen and S. C. Israel, Polymer, 19, 1157, 1978. 22. A. Laschewsky and I. Zerbe, Polymer, 32, 2070, 1991. 23. M. L. Pujol-Laure and J. C. Galin, Polymer, 35(7), 1462, 1994. 112


24. C. Gingreau and J. C. Galin, Polymer, 35(21), 4669, 1994. 25. Y. Chevalier, F. Melis and J. P. dalbiez, J. Phys. Chem., 96, 8614, 1992. 26. P. G. Apen and P. G. Rasmussen, J. polym. Sci. Polym. Chem., 30, 203, 1992. 27. E. A. Boucher, Prog. Polym. Sci., 6, 63, 1978. 28. A. B. Lowe, N. C. Billingham and S. P. Armes, Chem. Commun., 1555, 1996. 29. A B. Lowe, N. C. Billingham and S. P. Armes, Macromolecules, 32, 2141, 1999. 30. A. B. Lowe, PhD Thesis, Sussex University, Brighton, 1997. 31. Z. Tuzar, H. Pospisil, J. Plestil, A. B. Lowe, F. L. Baines, N. C. Billingham and S. P. Armes, Macromolecules, 30, 2509, 1997. 32. M. Vamvakaki, N. C. Billingham and S. P. Armes, Polymer, 39(11), 2331, 1998. 33. a) H. C. Brown, J. Chem. Soc. 1248, 1956. b) H. C. Brown, J. Am. Chem. Soc., 67, 1452, 1945. c) H. C. Brown, J. Am. Chem. Soc., 67, 378, 1945. d) H. C. Brown, J. Am. Chem. Soc., 66, 435, 1944. 34. N. Menschutkin, Z. Physik. Chem., 5, 589, 1890. 35. V. Bütün, C. E. Bennett, M. Vamvakaki, A. B. Lowe, N. C. Billingham and S. P. Armes, J. Mater. Chem., 7(9), 1693, 1997. 36. S. Hashimoto, T. Yamashita and M. Kaneda, Polym. J., 6, 238, 1974. 37. S. Hashimoto and T. Yamashita, Polym. J., 8, 15, 1976.

113

Chapter 4-Selective quaternisation

CHAPTER 4.

Selective Quaternisation of Tertiary Amine Methacrylate Copolymers and Their Aqueous Solution Properties

4.1 INTRODUCTION

113


Polymers derived from aminoalkyl (meth)acrylates have broad industrial applications as adhesives, coatings, textile treatments, hair conditioner formulations, flocculants etc.1-2 and have been one of the most extensively studied classes of cationic polyelectrolytes. Cationic polyelectrolytes can be easily synthesised either from the quaternisation of precursor polymers using alkyl halides3-7 or from the polymerisation of the quaternary Ncontaining monomeric salts, derivatised from aminoalkyl methacrylates and acrylamides, vinyl amines, vinyl pyridines etc. via classical free radical polymerisation.1,8-15

Considerable research on the quaternisation of (4-vinyl pyridine)-based copolymers containing a hydrophobic block, such as poly(styrene),16-24 poly(dimethylsiloxane),3 PMMA25 or poly(2-methyl styrene)26 have been carried out using various alkyl halides and their solution properties were investigated in both aqueous16-20 and organic media.26 Aggregation numbers of the micelles depended on both the nature of the solvent and the alkylating reagents.19 Brown and Cahn27 have investigated the effect of different alkyl halides on the kinetics of quaternisation of vinyl pyridines. They found that the rate constant decreased and the activation energy increased in the order methyl, ethyl, isopropyl iodide. The increased activation energies were attributed to an increase in steric hindrance with increasing branching of the alkyl halide. In addition, the unimolecular SN1 mechanism takes precedence over the bimolecular SN2 mechanism for more branched alkyl halides in ionising solvents. Similar increases on the activation energies of the quaternisation of P4VP with ethyl iodide, n-butyl iodide and n-hexyl iodide were reported by Boucher et al.24,28 In addition, an important solvent effect has been observed in the quaternisation of poly(4-vinyl pyridine) with n-butyl bromide by Arcus and Hall.29 While in tetramethyl sulfone the reactivity decreased with conversion, in dimethylformamide the reaction was second order, and the rate constant remained unchanged during the reaction. Menschutkin30 originally reported the quaternisation of tertiary amines in 1890’s. Indeed, the conversion of tertiary amines to quaternary salts is called the ‘Menschutkin’ reaction. The rate of the Menschutkin reaction decreases for more sterically crowded alkyl groups on either the tertiary amine residues or the alkylating reagents, as mentioned in Chapter 3.

114


R3N

+

_ + R'R3N X

R'X

Several groups have reported the synthesis of quaternised PDMA: this may be achieved either by quaternising DMA monomer prior to polymerisation or by modifying the polymer itself.8, 31-33 Pradny and Sevcik have studied the effect of (a) varying the tacticity of the PDMA33 and (b) various organic solvents7 on the quaternisation reaction with alkyl halides. They also reported that the interactions between carbonyl and amino groups in PDMA play an important role in quaternisation.32

[

CH3

O ... C

]

[

R

......... N

CH3

C

R

] O.

..

H

O O

CH2

+N O

H2 C

CH2

CH2

R R

Nagai and co-workers have extensively studied the radical polymerisation of surface active long-chain alkyl salts of DMA and their application in the polymer encapsulation of silica particles.10-15 Yasuda et al. has also studied the polymerisation of DMA-CnBr quaternised with C8, C12, C14, C16, C18 in water and in organic solvents.34 These cationic polymers obtained from surface active higher alkyl salts of DMA are waterinsoluble. Leemans et al. has used quaternised DMA-MAA diblock copolymers as an emulsifier in the emulsion polymerisation of MMA.35 Hunkeler and Hamielec have synthesised copolymers of acrylamide with various quaternary ammonium cationic monomers via an “inverse-microsuspension copolymerisation”.36 In addition, Deboudt et al. have synthesised hydrophilic-hydrophilic DMA-NVP statistical copolymers and then DMA residues were quaternised with octyl, dodecyl or hexadecyl bromide in order to get hydrophobic DMA domains.4-6 An alternative method to obtain cationic DMA monomer is to use dimethyl sulphate as a quaternising reagent. Both Bogoeva-Gaceva8 and Liaw et al.1 have synthesised quaternised monomers with DMS. Subsequent polymerisation yielded poly(dimethylsulphate quaternised DMA) homopolymer which was used as a cationic flocculant for bentonite clays.

115


As far as we are aware, there have been no studies of the effect of varying the alkyl groups of poly(tertiary amine methacrylate)s on the polymer-analogous quaternisation reaction with different alkyl halides. Tertiary amines are weak bases. Their basicity depends on the polar effect of the alkyl groups, which increases in the series: ammonia, methylamine and ethylamine.37-40 It might be expected that the reactivity of the tertiary amine should increase with its basicity. However, their reactions with alkyl halides do not follow this trend. This is presumably due to the steric effects of the alkyl groups as studied by Menschutkin in the 1890’s. Brown has studied the steric strain of tertiary amines: it was found that the steric requirements of three ethyl groups are far larger than those of three methyl groups and therefore result in much larger steric congestion in the addition compound.37

In the present work, the quaternisation of DMA, DEA, DPA and MEMA homopolymers was investigated using various alkyl halides. More importantly, the DMA residues in DMA-DEA, DMA-MEMA, DMA-DPA diblock copolymers have been selectively quaternised using either MeI or BzCl. The micellisation of these novel cationic diblock copolymers has been investigated using various techniques including NMR spectroscopy, surface tensiometry and DLS.


116


4.2.1 The Synthesis of Tertiary Amine Methacrylate Homopolymers and Block Copolymers

See sections 2.2.3 and 2.2.4 for the general method used for the syntheses of the tertiary amine methacrylate homopolymers and block copolymers, respectively. In the latter case, DMA was always polymerised first, followed by the addition of DEA, DPA or MEMA.

4.2.2 Quaternisation of the Tertiary Amine Methacrylate Homopolymers

The quaternisation of all homopolymers was examined in both THF and H2O by reacting with a two-fold excess of methyl iodide (MeI), benzyl chloride (BzCl) or n-butyl iodide (BuI) at room temperature (for MeI) and reflux temperature (for BzCl and BuI). First, 2 grams of one of the homopolymers from each series was dissolved in either water or THF (40 ml) and the quaternising agent was then added to the solution at 20oC. Methylation of the DMA residues was very fast and was completed within 10-20 minutes. However, methylation of the DEA homopolymer required 2-3 h, the MEMA homopolymer required ca. 10 h under the same conditions. Quaternisation of DPA homopolymer with MeI was complete after refluxing in THF for 4-6 days. On the other hand, both benzylation and butylation of the DMA homopolymer required at least 1 day at reflux in THF. All the resulting quaternised homopolymers were insoluble in THF and excess quaternising agent was readily removed by soxhlet extraction with THF. All homopolymers were successfully methylated in THF. In addition, the hydrophilic DMA and MEMA homopolymers were also quaternised in aqueous media using MeI.

4.2.3 Selective Quaternisation of the DMA Residues in the Block Copolymers.

Selective quaternisation of DMA residues in the DMA-DEA, DMA-DPA and DMAMEMA block copolymers (1-2 g) was carried out using a stoichiometric amount of MeI (based on the DMA content of the block copolymers) in THF at 25oC for 24 h. Benzylation required reflux in THF up to 48 h. The copolymers were generally purified by soxhlet extraction with THF to remove excess quaternising reagent. In the case of the selectively quaternised DMA-MEMA block copolymer, purification was achieved simply by precipitation in n-hexane. The resulting selectively methylated block copolymer was

117


dried in a vacuum oven at 55oC for 2 days. The extent of quaternisation was assessed by 1

H NMR spectroscopy.

4.2.4 Quaternisation of the Second Block (DEA, MEMA or DPA) of Selectively Betainised

Diblock Copolymers.

After selective betainisation of the DMA residues in either the DMA-DEA, DMA-MEMA or DMA-DPA block copolymers, the second block was successfully quaternised in aqueous media. Typically, the selectively betainised block copolymer (1-2 g) was dissolved in deionised water (pH 6-7) in a single-necked 100 ml round bottomed flask. A two-fold excess of MeI (based on the residues in the second block) was then added via syringe and the aqueous solution was stirred for at least 1-4 days at 20oC, depending on the nature of the second block. The resulting betainised-quaternised block copolymer was precipitated from aqueous solution into THF in order to remove the excess quaternising agent.


4.3.1 Gel Permeation Chromatography

Molecular weights and molecular weight distributions of all precursor (co)polymers were determined by gel permeation chromatography (GPC). The GPC set-up consisted of a Perkin Elmer LC pump and a RI detector, the columns used was either Mixed ‘E’ or Mixed ‘D’ (Polymer Labs), and calibration was carried out using PMMA standards (Polymer Labs). The GPC eluent was HPLC grade THF stabilized with BHT, at a flow rate of 1 mL min-1. Molecular weights of the selectively quaternised diblock copolymers were calculated assuming 100 % quaternisation.

4.3.2 Nuclear Magnetic Resonance Spectroscopy (NMR)

The compositions of all precursor block copolymers and the micellisation behaviour of the selectively quaternised diblock copolymers in aqueous solution were investigated using either a Bruker AC-P 250 MHz or 350 MHz instrument in D2O/NaOD and

118


D2O/DCl. Block copolymer compositions were determined by comparing the integrals assigned to the different comonomers (see Sections 2.4.3.2 and Section 2.4.3.3).

4.3.3 Turbidimetry

A PC-controlled Perkin Elmer Lambda 2S UV/VIS spectrometer was used to determine the effect of varying both the copolymer compositions and molecular weights of the DMA-MEMA block copolymers on their critical micellisation temperatures. See section 2.3.3 for the experimental conditions.

4.3.4 Dynamic Light Scattering Studies (DLS):

The hydrodynamic size of the selectively quaternised block copolymers in aqueous solution was measured using dynamic light scattering. See Section 2.3.5 for a description of the experimental conditions.

4.3.5 Surface Tensiometry:

Surface tension measurements were carried out using a Kruss K10ST surface tensiometer equipped with a platinum ring. Either the copolymer concentration of the selectively quaternised block copolymers or the solution pH were varied (the latter was measured using a Corning Check-Mite pH sensor calibrated with pH 4, 7 and/or 10 buffer solutions).

4.4 RESULTS AND DISCUSSION

4.4.1 Quaternisation of Tertiary Amine Methacrylate Homopolymers

Quaternisation of the four homopolymers was examined in both THF and water using three alkyl halides, methyl iodide (MeI), n-butyl iodide (BuI) and benzyl cloride (BzCl) (see Figure 4.1) to produce cationic polyelectrolytes. The results are summarised in Table 4.1. The three DMA, MEMA and DEA homopolymers reacted readily with MeI at room temperature in both THF and H2O (with the exception of DEA in H2O). Quaternisation of

119


DMA with MeI was rapid in both solvents and was essentially complete within 10-20 minutes at 20oC. Quaternisation of DEA homopolymer was complete within 2-4 h in THF at 20oC and MEMA homopolymer was quaternised after 6-10 h in THF (or after 1-2 hours in water). DPA homopolymer required elevated temperature (45oC) and a longer reaction time (4 days) for complete quaternisation with MeI in THF (see Table 4.1). CH3 ( CH2 C ) x C O

THF, 25oC R-X

( CH2 C ) x C O

O

O

CH2

CH2

CH2

CH2 X+ H3C N CH3

N H3C

CH3

CH3

R

DMA homopolymer

R : CH3I,

quaternised-DMA homopolymer CH2Cl, nBuI

Figure 4.1 Reaction scheme for the quaternisation of the tertiary amine methacrylate homopolymers. Only DMA homopolymer could be quaternised with BuI and BzCl, even under reflux for 2 days. Both DPA and MEMA homopolymers did not react with BuI and BzCl, even reflux for 2 days. Only 5-10 mol% of the DEA residues in the homopolymer reacted with BzCl at reflux temperature in THF for 2 days. Quaternisation of both DEA and DPA homopolymers was not possible in aqueous media due to their insolubility. On the other hand, under micellar conditions, all residues could be quaternised with MeI. This will be discussed later.

Polymers derivatised in THF with both MeI and BuI were typically yellow. White polymers were obtained using MeI in aqueous media. Thus water was preferred for derivatisations with MeI in some cases, even though this reagent is not very soluble in this solvent.

120


For the DMA homopolymers derivatised with MeI, degrees of quaternisation of 100% (see Table 4.1) were calculated using

1

H NMR spectroscopy. The quaternary

trimethylamino proton signal (at δ 3.3) was compared to that of the unquaternised dimethylamino protons at δ 2.3-2.4. The absence of the peak at δ 2.3-2.4 or its shift to δ 3.3 indicated 100% quaternisation. In the quaternisation of all homopolymers, a two-fold excess of alkyl halides (based on the residues in the homopolymers) were used and quaternisation degrees of 100% were obtained from methylation of the four homopolymers and also for both benzylation and butylation of the DMA homopolymers.

Table 4.1 Number-average molecular weights, calculated number-average molecular weights, degree of quaternisation, observed precipitation time and reaction conditions of four tertiary amine methacrylate homopolymers. Quaternisation was carried out using MeI, BzCl and BuI, respectively. Sample Code

Polymer

VB128 VB133

Me-DMA Me-DMA

VB130

MeMEMA MeMEMA

VB135

Precursor Calcd. Reaction Observed Reaction Degree of Mn a Mn b Media Precipitation Conditions quaternisation c (g mol-1) (g mol-1) Time (%) 4,000 4,750

7,600 9,050

THF H2O

10 min. soluble

25oC, 24 h 25oC, 24 h

100 100

12,100

20,700

THF

6h

25oC, 24 h

100

12,100

20,700

H2O

soluble

25oC, 24 h

100

VB131 VB131 VB144

Me-DPA Me-DPA Me-DPA

4,800 4,800 4,800

-----6,900 8,000

THF THF THF

---24 h 24 h

25oC, 24 h 45oC, 48 h 45oC, 144h

0 65 100

VB129

Me-DEA

11,000

19,450

THF

1h

25oC, 24 h

100

o

VB141 VB142 VB143

Bz-DMA Bz-DEA Bz-MEMA

4,750 3,550 12,100

8,600 -------

THF THF THF

3h -------

65 C, 48 h 65oC, 48 h 65oC, 48 h

100 5-10 0

VB158 VB159 VB160

Bu-DMA Bu-DEA Bu-MEMA

4,000 3,550 12,100

8,700 -------

THF THF THF

5h -------

65oC, 48 h 65oC, 48 h 65oC, 48 h

90 5-10 0

a: As determined by GPC (calibrated with poly(methyl methacrylate) standards) b: As calculated from GPC results of precursor homopolymers c: As determined by 1H NMR spectroscopy

Figure 4.2a shows the corresponding 1H NMR spectrum of the DMA homopolymer in D2O with relevant signals labelled. Peak C at δ 2.3-2.4 represents the six dimethylamino protons. After quaternisation of this homopolymer with MeI (see spectrum b), nine

121


quaternary amine protons appear at δ 3.3. The absence of any unquaternised dimethylamino protons at δ 2.3-2.4 in ‘spectrum b’ indicates 100% quaternisation.

CH 3

A)

C

( CH 2

)x

C C

O

O CH 2 A

B

CH 2 B

A

N CH 3 C

C H 3C

5 .0

4 .5

4 .0

3 .5

3 .0

2 .5

2 .0

1 .5

1 .0

CH3

B)

C

( CH2

C

)x

C

O

O CH2 A CH2 B

A

C H 3C

B

I+

CH3 C

N

CH3 C

5.0

4.5

4.0

C)

3.5

3.0

2.5

2.0

1.5

1.0

CH3

E

( CH2

C )x

C

O

C O

CH2 A CH2 B Cl + C H3C N CH2 D CH3 C

8 .0

7 .0

A+D B E

6 .0

5 .0

4 .0

3 .0

2 .0

1 .0

CH3

D)

( CH2

C

C C

)x O

O

G

CH2 A CH2 B I+ C H3C N CH2 D CH3 C

A

5 .0

B

4 .0

D

U nquate rnise d DMA

3 .0 δ/p p m

122

CH2 E

CH2 F

CH3 G

E

F

H

2 .0

1 .0


Figure 4.2 1H NMR spectra of (a) precursor and (b-d) quaternised DMA homopolymers in D2O. Quaternisation was carried out using (b) methyl iodide, (c) benzyl chloride and d) n-butyl iodide, respectively. In addition, Figure 4.2c shows the benzylated DMA homopolymer spectrum in which all DMA residues are benzylated (the degree of quaternisation was calculated by comparing five aromatic protons at δ 7.5 with six dimethylamino protons at δ 3.1. In the case of quaternisation with BuI, comparing the six equivalent quaternary methyl protons (at δ 3.3) with the unquaternised dimethylamino protons at δ 2.4-2.5 indicated a degree of quaternisation of 90%. Thus, the quaternisation of DMA homopolymer was successfully carried out with MeI at room temperature within a reasonably short time (20-60 min) and with both BzCl and BuI in refluxing THF within 2 days.

A)

D 2O/DCl (pH 2)

CH 3

( CH 2

C

)x

C

O

C O CH 2 A CH 2 B

B A

D

N+

Cl

C H2C

CH 2 C

D H 3C

CH 3 D

123

D


B)

D 2O/DCl (pH 2)

CH3

( CH2

C

)x

E

D

O

C O

CH2 A CH2 B

C E H3C

A

5.0

B

4.5

4.0

3.5

3.0

N+

I

C H2C

CH2 C

D H3C

CH3 D

2.5

δ/ppm

2.0

1.5

1.0

Figure 4.3 1H NMR spectrum of DEA homopolymer; a) before quaternisation (D2O/DCl), b) after quaternisation with MeI (D2O/DCl). After quaternisation of the DEA homopolymer, the peaks of all the diethylaminoethyl protons are shifted downfield from δ 3.3, 3.6 and 3.9 (see Figure 4.3a) to δ 3.5, 3.8 and 4.5 (see Figure 4.3b), respectively. A new peak appeared at δ 3.1-3.2 due to the quaternary methyl group. This was compared with the other peaks to determine the degree of quaternisation. Quaternisation was calculated to be approximately 100% methylation.

D

CH3

( CH2

CH3

C )

x

C

O

O

CH2

CH

A B

CH2 H C

CH3 Cl + D N

C

C CH3

A

B

C

124

D

CH3 D


D CH3

( CH2

x

C

O

O

CH2

CH

A

E A

5.0

A)

4.5

B

4.0

D2O/DCl (pH 2)

D

CH3

C )

CH2 B

H C

C

I-

CH3

+ N CH3 E CH3

C CH3

D

C

3.5

3.0

2.5

δ/ppm

2.0

1.5

1.0

Figure 4.4 1H NMR spectra of DPA homopolymer in D2O/DCl (pH 2): a) before quaternisation; b) after quaternisation with MeI.

Like the DEA homopolymer spectra, the DPA protons are also shifted downfield from δ 3.4-3.5, 3.8 and 4.3-4.4 (see Figure 4.4a) to δ 3.5-3.6, 3.9 and 4.3-4.4 (see Figure 4.4b) respectively. The degree of quaternisation was determined by comparing the peak integrals of the quaternary methyl proton signal at δ 2.8-2.9 to that of the four equivalent

B) D2O/DCl methyl groups at δ (pH 1.4. 2) The degree of quaternisation was calculated to be 65% after 2 days in refluxing THF and 100% after 6 days. For the quaternised MEMA homopolymer, similar downfield shifts from δ 2.6, 2.8, 3.8 and 4.2 (see Figure 4.5a) to δ 3.7, 4.1, 4.2 and 4.6 (see Figure 4.5b) were observed. The quaternary methyl protons are at δ 3.4 (see Figure 4.5B. The absence of any peak at around δ 2.5-2.8 in spectrum B suggested 100% quaternisation. Comparing the integrals of peaks E and A also suggested that quaternisation was complete.

125


CH 3

A)

D

C

( CH 2

C C

)x O

O CH 2 A CH 2 B

B

N

A

CH 2 C

C H 2C

CH 2 D

D H 2C O

5.0

4.5

4.0

3.0

3.5

2.5

δ/ppm

2.0

1.5

1.0

2.0

1.5

1.0

CH 3

B) D

( CH 2

E

C )

x O

C O

C

CH 2 A CH 2 B

E H 3C

B

N + I-

A

CH 2 C

C H 2C

CH 2 D

D H 2C O

5.0

4.5

4.0

3.5

3.0

2.5

δ/ppm

Figure 4.5 1H NMR spectra of MEMA homopolymer in D2O: a) before quaternisation, b) after quaternisation with MeI Table 4.2 A summary of attempted quaternisation of the four tertiary amine methacrylate homopolymers with alkyl halides in either THF or water. Degree of quaternisation (%) Alkyl halides

PDMA

PDEA

PDPA

PMEMA

Solvent

MeI

100 100

100 --- b

100a --- b

100 100

THF water

BzCl

100a

(5-10)a

0

0

THF

BuI

90a

0

0

0

THF

a) Under reflux for 2 days b) Both DEA and DPA homopolymers are insoluble in water. 126


In summary, quaternised DMA homopolymer was obtained in either THF or water with MeI at room temperature within 20-30 minutes, with BzCl in refluxing THF within 2 days and with BuI under reflux within 2-3 days. Quaternisation of DEA homopolymer is possible only with MeI (THF, room temperature and 2 h). Quaternisation of DPA homopolymer requires high temperature and long reaction times to get 100% quaternisation. MEMA is also quaternised in THF at room temperature within 6-8 h. The degrees of quaternisation of the homopolymers obtained with different alkyl halides is summarised in Table 4.2.

The much higher reactivity of the DMA homopolymer towards quaternisation suggests that selective quaternisation of DMA residues in the block copolymers should be feasible. This possibility is explored below. As studies by many researchers, an incerase of the length of the alkyl groups, in either alkylating agent or amine residues, decrease the rate of quaternisation. The reaction is faster with smaller alkyl halides. In the case of longer alkyl groups of the tertiary amine residues, steric congestion is more important than the basic strength of the tertiary amine.

4.4.2 Selective Quaternisation of the Tertiary Amine Methacrylate Block Copolymers and Their Micellisation Studies. As mentioned in Chapter 2, micelles of DMA-DEA and DMA-DPA block copolymers precipiteted from aqueous media at around pH 7-9 due to the decrease in solubility of the DMA corona with increasing solution pH. As the water solubility of the derivatised cationic DMA block is much higher than that of the precursor, quaternised block copolymer micelles should be stable across a much wider pH range. Thus, selective quaternisation of DMA residues in DMA-DEA, DMA-DPA and DMA-MEMA block copolymers was attempted using both MeI and BzCl (see Figure 4.6).

127


CH 3

CH 3 ( CH 2

H 3C

C )x C O

( CH 2

C )y C O

C )x C O

( CH 2

C )y C O

O

O

O

CH 2

CH 2

CH 2

CH 2

CH 2

CH 2

N

R1

R1

R2 N

H 2C

CH 2

H 2C

CH 2

H3C

CH 3

H 2C

CH 2

CH 3I,

CH 2

CH 2 X + H3C N CH 3

CH 3

DEA

R2 :

( CH 2 R2-X

O

N

R1 :

CH 3

CH 3

THF, 25 oC

H3C

CH 3

N C

C O

H3C

H

MEMA

Selectivelly quaternised block copolymer

CH 3

H

DPA

CH 2Cl

Figure 4.6 Reaction scheme for the selective quaternisation of the tertiary amine methacrylate block copolymers. 4.4.2.1 Selective Quaternisation of DMA Residues of DMA-DEA Block Copolymers. Preliminary quaternisation experiments on the DEA and DMA homopolymers confirmed that the DEA homopolymer required much longer reaction times with MeI (2-4 h) and had only a low quaternisation degree (10 %) with BzCl after reflux for 2 days. These observations suggested that the DMA residues in the DMA-DEA block copolymer could be selectively quaternised provided that suitably mild conditions were employed and a stoichiometric (rather than a two-fold excess) amount of the alkylating reagent was employed. The results are summarised in Table 4.3. Table 4.3 A summary of block copolymer compositions, molecular weights, and micelle diameters of selectively quaternised DMA-DEA and DMA-DPA block copolymers. Quaternisation was carried out using both MeI and BzCl. Micellisation was at pH 12 and 20oC. Sample Code

Selectively Quaternised Block copolymer

DMA Contenta (mol %)

Precursor Mnb (g mol-1)

VB186

Me-DMA-DEA

34

35,000

44,600

23

VB153

Bz-DMA-DEA

50

15,000

20,550

15

128

Calcd. Micelle Mn c Diameterd (g mol-1) (nm)


VB154 VB155

Bz-DMA-DEA Bz-DMA-DEA

78 49

12,400 9,550

19,900 13,000

-----

VB139 VB138 VB140

Me-DMA-DPA Me-DMA-DPA Me-DMA-DPA

82 72 61

11,550 12,050 15,750

19,550 19,200 23,200

14 27 33

VB223 VB156

Bz-DMA-DPA Bz-DMA-DPA

82 72

11,550 11,800

18,700 18,000

15 30

a: As determined by 1H NMR spectroscopy b: As determined by GPC (calibrated with poly(methyl methacrylate) standards) c: As calculated from GPC analyses of precursor polymers assuming 100% quaternisation d: As determined by PCS on 1.0 % aqueous solutions

Degrees of quaternisation of the DMA residues were confirmed to be 100% by 1H NMR studies. As can be seen in Figure 4.7, all peaks corresponding to both blocks of a 49:51 DMA-DEA copolymer are present in ‘spectrum a’ (recorded in D2O/DCl at pH 2). After benzylation (see spectrum b), the peak I at δ 7.5 corresponds to aromatic protons and its integral was compared to the peak integral C at δ 3.1-3.2 in order to determine a degree of quaternisation of 100%. As the solution pH was increased to pH 10, the peaks labelled E, F and G corresponding to DEA residues disappeared (see spectrum c). This indicates that the DEA block becomes dehydrated and forms the micelle core, while the benzylated DMA block forms the micelle corona. In contrast, under these conditions, the precursor block copolymer is not soluble and precipitates from aqueous solution.

129


CH3

CH3

( CH2

D

C

) 0.49

C

O

( CH2

C

) 0.51

C

O

O

O

CH2 A

CH2 D

CH2 B _ Cl N+

CH2 E _ N + Cl

CH3 C

H3C C

D F H2C

CH2 F

G H3C

CH3 G

C

G

B+E F A+D

A) Precursor at pH 2 CH 3

CH 3

(

CH 2

C

) 0.49

C

O

C

) 0.51

C

O

O

O

CH 2 A

CH 2 D

_ CH 2 B Cl + C H3C N CH 3 C CH 2 H

E

( CH2

I

D

CH 2 E _ N + Cl

F H 2C

CH 2 F

G H 3C

CH 3 G

C

G

F ADH

B) After quaternisation at pH 2

E B

No E, F

No G

C) After quaternisation at pH 10

8.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

δ/ppm Figure 4.7 1H NMR spectra of selectively quaternised 49:51 DMA-DEA block copolymer with BzCl in D2O a) precursor block copolymer at pH 2, b) after quaternisation and at pH 2, c) after quaternisation and at pH 12. (Note disappearance of the E, F and G peaks due to micellisation of the unquaternised DEA block).

130


The micelle diameter measured by PCS is around 20 nm, which is slightly lower than the micelle diameter of the precursor micelles. Micelles with narrower polydispersities were observed at higher DEA contents. The micelle diameters are summarised in Table 4.3.

70

(a)


65 AFTE R Q U A TER N ISATIO N

60 55 50 45 40

Precipitation Precursor D M A-D EA block copolym er

35 30 0

2

4

6

8

10

12

pH 75

(b)

70


65 60 55 AFTER Q U A T E R N IS A T IO N

50 45 40

D M A -D E A block copolym er B efore quaternisation

35 30 0.0

0.2

0.4

0.6

C opolym er concentration (w /v% )

Figure 4.8 Variation of surface tension with (a) pH for a 0.2 w/v% aqueous solution of 78:22 DMA:DEA block copolymer; (b) as a function of copolymer concentration at pH 8.5. Note that quaternisation of DMA residues dramatically reduces surface activity of these DMA-DEA block copolymers.

131


Surface tensiometry measurements on the 72:28 DMA-DEA block copolymer indicated that the surface activity has a strong pH dependence as reported in Chapter 2. At high pH, the block copolymer becomes significantly more surface active (the limiting surface tension is ca. 32-34 mN/m). Presumably, the deprotonated hydrophobic DEA block becomes adsorbed strongly at the air-water interface, thus lowering the surface tension of the solution. After quaternisation, the limiting surface tension of the block copolymer increased to 55 mN m-1 (see Figure 4.8a). This is presumably due to the increased watersolubility of the DMA block with quaternisation, which decreases the adsorption of the block copolymer at the air-water interface. The CMC point of the 72:28 DMA-DEA block copolymer is around 0.02 w/v% as calculated from the surface tension versus copolymer concentration curve. After quaternisation of the DMA residues in this block copolymer, its surface activity decreased appreciably (see Figure 4.8b), indicating reduced adsorption at the air-water interface. In addition, the CMC of the quaternised DMA-DEA block copolymer is 0.3 w/v%, which is significantly higher than the CMC of the precursor block copolymer. Clearly, quaternisation of these copolymers decreases their surface activity.

4.4.2.2 Selective Quaternisation of DMA Residues of DMA-DPA Block Copolymers.

As can be seen in Table 4.1, quaternisation of DPA homopolymer with MeI requires significantly longer reaction times and higher temperatures. Thus, selective quaternisation of the DMA residues in a 61:39 DMA-DPA copolymer was successfully carried out with MeI in THF at room temperature for 24 h and with BzCl in refluxing THF for 48 h.

Figure 4.9 shows the NMR spectrum of the 61:39 DMA-DPA precursor block copolymer (see spectrum a) in D2O/DCl (pH 2). Under these conditions, both blocks are soluble since the DPA residues are protonated. After quaternisation of the DMA residues with MeI (see spectrum b), it is clear that all the DMA residues are quaternised due to the absence of any unquaternised tertiary amine protons at δ 2.9-3.0. In addition, the quaternary methyl protons are present at δ 3.2-3.3 in ‘spectrum b’. The peak integral of peak C at δ 3.2-3.3 was compared with peak integral G due to the DPA residues in order to determine the block composition. The calculated block composition was the same as the precursor block composition, which indicates that all the DMA residues were quaternised. As the solution pH is increased (pH 9), the disappearance of the peaks due to

132


the DPA residues at δ 1.3-1.4 indicated that the DPA block becomes dehydrated and forms the micelle cores, with the quaternised DMA block formed the solvated micelle corona (see spectrum c).

CH 3

CH 3

(

CH 2

C

) 0.61

C

( CH 2

O

C C O

O CH 2 A

G

) 0.39 O CH 2 D

C H 3C

CH 2 E

C

H F

-

H F

CH 3

G

CH 3 C

N

C

+ Cl N D

H 3C

CH 2 B I+

CH 3 H 3C

CH 3 C

G C

C Precursor block copolymer

a) pH 2

B+E A D

F

b) pH 2

After quaternisation no G

4.5

4.0

3.5

3.0

2.5

2.0

1.5

c) pH 9

1.0

δ/ppm Figure 4.9 1H NMR spectra of (a) a 61:39 DMA-DPA precursor block copolymer, (VB140, Mn = 23,200 g mol-1) in D2O/DCl at pH 2; (b) the same copolymer, after selective quaternisation using MeI (D2O/DCl at pH 2); (c) the selectively quaternised copolymer at pH 9.

PCS studies confirmed that the micelle diameters of the quaternised DMA-DPA block copolymer were between 14-33 nm depending on the block composition (see Table 4.3). As the DPA content was increased, larger micelle diameters were obtained. Unlike the precursor copolymer micelles, the micelles with selectively quaternised copolymers were stable at high pH and no precipitation was observed even at pH 12-13. In addition, quaternisation of the DMA residues does not lead to large differences in micelle diameters compared to those obtained with the precursor copolymers.

133


4.4.2.3 Selective Quaternisation of DMA Residues of DMA-MEMA Block Copolymers. It is difficult to get stable DMA-MEMA block copolymer micelles with the MEMA block forming the micelle core at high temperature. As discussed in Chapter 2, this is due to the small temperature difference (5-10oC) between the cloud points of these two blocks. If one block can be made more soluble, then micellisation should be possible, with the more soluble block forming the solvated corona at higher temperatures. In principles, selective betainisation (see Chapter 3) or quaternisation of the DMA residues should produce much greater solubility differences between the two blocks. Thus, selective quaternisation of the DMA residues was carried out using MeI and BzCl; these derivatisations are summarised in Table 4.4. Table 4.4 A summary of block copolymer compositions, molecular weights, solution conditions and micelle diameters of selectively quaternised DMA-MEMA block copolymers. Block Copolymer ID

DMA Mn of Mn of Temp. Contenta Precursorb quaternised (oC) (mol %) (g mol-1) copolymer c (g mol-1)

Salt Conc. (mol dm-3)

Micelle Diameter d (nm)

Me-DMA-MEMA block copolymer VB137 VB136 VB136 VB132 VB132 VB132 VB132

59 46 46 35 35 35 35

31,150 25,500 25,500 36,000 36,000 36,000 36,000

46,100 34,750 34,750 45,700 45,700 45,700 45,700

25 25-65 25 25-65 25 < 56 > 56

0.9 M Na2SO4 0.08 M Na2SO4 1.2 M Na2SO4 no salt 0.8 M Na2SO4 0.06 M Li2SO4 0.06 M Li2SO4

37 unimer 27 unimer 39 unimer 34

25 25-65 25-65 25-65 25-65 25 25-65 25-65

1.0 M Na2SO4 0.08 M Na2SO4 no salt pH 7-8 no salt pH>10 0.15 MNa2SO4 0.6 M Na2SO4 no salt 0.9 M Na2SO4

24 unimer unimer uni-35 uni-35 33 unimer 10-16

Bz-DMA-MEMA block copolymer VB157 VB157 VB220R VB220R VB220R VB220R VB225 VB225

48 48 40 40 40 40 36 36

21,550 21,550 27,600 27,600 27,600 27,600 5,200 5,200

28,850 28,850 35,000 35,000 35,000 35,000 6,500 6,500

a: As determined by 1H NMR spectroscopy b: As determined by GPC (calibrated with poly(methyl methacrylate) standards) c: As calculated assuming 100% quaternisation d: As determined by PCS on 1.0 % aqueous copolymer solutions at 25oC.

134


Figure 4.10 shows the spectra of a 46:54 DMA-MEMA block copolymer in D2O before (spectrum a) and after quaternisation of the DMA residues (spectra b and c). The signal at δ 2.4 in ‘spectrum a’ is due to the six dimethyl amino protons of the DMA residues, whereas the signal at δ 2.5-2.8 corresponds to the six -CH2- protons bound to nitrogen in the MEMA residues. After quaternisation with MeI, nine quaternary amine protons associated with the DMA residues appeared at δ 3.3 (see spectrum b). Comparing this peak integral with that of the MEMA signal in ‘spectrum b’ gives the same 46:54 copolymer composition as that determined for the original DMA-MEMA precursor block copolymer from ‘spectrum a’. This confirms that the DMA residues were selectively quaternised, as expected given the differing reactivities of the DMA and MEMA residues towards MeI observed in the homopolymer derivatisation. CH3

CH3

( CH2

C

C

) 0.46

C

O

( CH2

C

)0.54

C

O

O

O

CH2 A

CH2 D CH2 E

CH2 B I+ C H3C N CH3 C CH3 C

Precursor block copolymer

N CH2 F

F H2C

CH2 G

G H2C O

a) G A

D

F

B

E

After quaternisation b)

A

No D

No E and F

B 4.0

3.0

δ/ppm

1.0 M K2CO3 2.0

c) 1.0

Figure 4.10 1H NMR spectra of a selectively quaternised 46:54 DMA-MEMA block copolymer in D2O, a) before selective quaternisation, b) after selective quaternisation, c) after selective quaternisation and in the presence of 1 M K2CO3

135


As reported in Chapter 2, MEMA homopolymer can be precipitated (salted out) from aqueous solution even at relatively low salt concentrations, e.g. 0.1-0.2 M K2CO3 or Na2SO4. Near-monodisperse micelles with polydispersities lower than 0.05 were obtained in the presence of either K2CO3 or Na2SO4, with the cationic DMA blocks forming the solvated coronas and MEMA blocks forming the micelle cores (see Table 4.4). 1H NMR studies confirmed this interpretation since the MEMA signals, in ‘spectrum b’, disappeared in the presence of salt (see Figure 4.10, spectrum c) which is consistent with this block forming the dehydrated micelle cores. This micellisation is reversible: as the salt is removed via dialysis the MEMA block becomes solvated again. Micellisation studies with PCS indicated that micelle diameters were very similar to those observed for the precursor block copolymers (see Table 4.4). Micellar diameters were determined under three conditions: (1) in the presence of high salt concentration at room temperature; (2) in the presence of low salt concentration (0.06-0.15 M) at high temperature; and (3) at pH greater than 10 at high temperature. The micellar diameter was typically between 20-40 nm depending on chain length and solution conditions. 4.4.2.4 Partial Quaternisation of DMA Residues of Tertiary Amine Methacrylate Block Copolymers Partial quaternisation of the DMA residues in the diblock copolymers were achieved using MeI quaternising reagent. The degree of quaternisation was determined from 1H NMR specra by comparing the corresponding peak integrals. For the quaternised DMADEA, DMA-DPA and DMA-MEMA block copolymers, the peak integrals of the quaternised tertiary amine protons of the DMA residues at δ 3.3 were compared to that of the six methyl protons (δ 1.4) of the diethyl amino residues of the DEA block in the DMA-DEA block copolymer or to that of the four methyl groups (δ 1.4) of the diisopropylamino residues for the quaternised-DMA-DPA block copolymers or to that of the -CH2 protons bound to the nitrogen of the MEMA residues at δ 2.5-2.8. When substoichiometric amounts of MeI were deliberately used to derivatise the tertiary amine block copolymers, the DMA block became a statistical copolymer containing underivatised DMA and quaternised DMA residues. Dynamic light scattering studies confirmed that the partially quaternised DMA-MEMA, DMA-DEA and DMA-DPA block

136


copolymers also formed stable micelles without any precipitation even pH 13. The results are summarised in Table 4.5. Partial quaternisation increases the water solubility of the DMA block, which no longer exhibits a cloud point. In some cases, such as the syntheses of shell cross-linked micelles partial derivatisation can be beneficial and indeed essential. As mentioned in Chapter 2, temperature-induced micellisation of the DMA-based tertiary amine methacrylate block copolymers is not possible above pH 8 due to precipitation of DMA residues. In addition, partial quaternisation also allows and helps to control shell cross-linking of the unquaternised DMA residues in the micelle corona. This will be discussed in Chapter 5.

Table 4.5 A summary of block copolymer compositions, molecular weights, degrees of quaternisation, solution conditions and micelle diameters of selectively quaternised DMA-MEMA block copolymers. Sample code

VB169 VB203 VB220 VB220 VB172 VB172

Block copolymers

Me-DMA-MEMA Me-DMA-MEMA Bz-DMA-MEMA Bz-DMA-MEMA Me-DMA-MEMA Me-DMA-MEMA

DMA Mn Degree of pH Contenta Precursor Quaternisation (mol %) (g mol-1) b (mol%)a

Conc. of Temp. Micelle o Na2SO4 C Diameter -3 (mol dm ) (nm)c

48 40 40 40 35 35

21,550 27,600 27,600 27,600 36,000 36,000

40 30 66 66 30 30

8 12 12 8 8 8

0.25 ----0.6 0.1 0.1

60 60 65 25 20 50

24 22 29 32 unimer 23

VB164 Me-DMA-DEA VB168 Me-DMA-DEA

50 34

15,000 35,000

25 44

10 10

-----

22 23

20 23

VB205 Me-DMA-DPA

72

11,800

55

10

---

22

18

a: As determined by 1H NMR spectroscopy b: As determined by GPC (calibrated with poly(methyl methacrylate) standards) c: As determined by PCS on 1.0 % aqueous copolymer solutions at 25oC.

Figure 4.11 shows a 35:65 DMA-MEMA block copolymer before (see spectrum a) and after 30 mol% quaternisation (spectra b and c). In order to verify the degree of quaternisation of 30% of the DMA block, the peak integrals of the quaternised tertiary amine protons of the DMA residues at δ 3.3 were compared to that of the six methyl protons at δ 2.3 of the six dimethylamino protons of the unquaternised DMA residues (see spectrum b). As the solution temperature was increased to 60oC in the presence 0.1 M Na2SO4, the disappearance of the MEMA signals indicated that the MEMA blocks

137


became dehydrated and formed the micelle cores, while the partially quaternised DMA formed the solvated corona (see spectrum c). As the solution cooled to 25oC, the MEMA signals reappear, which confirms that the temperature-induced micellisation is fully reversible.

[(

CH3 CH2

C

) 0.10 ( CH2

C

C

O

) 0.25 ]

[(

CH 3 CH2

C

O

C

) 0.65 ]

C

O

O

O

O

CH2

CH2

CH 2

CH

b

CH3

2

CH2

a

H3C N CH 3 + _ I CH3

b

c

CH2

N

N

H 3C

CH3

d

d

b

e

f g

CH2

H2C

CH2

H 2C

f g

O

Precursor block copolymer

a+g

f

A

d

b c+e

Reduced g

4.0

Partially quaternized DMA-MEMA block copolymer at 25 oC

Reduced e and f

3.5

3.0

2.5

δ/ppm

138

B

Partially quaternised DMA-MEMA block copolymer micelles at 60 oC 2.0

1.5

C 1.0


Figure 4.11 1H NMR spectra (in D2O) of a precursor 35:65 DMA-MEMA block copolymer, b) after 30 mol% partial quaternisation of DMA residues, c) after partial quaternisation and in the presence of 0.1 M Na2SO4 at 60oC. 4.4.2.5 Quaternisation of Second Blocks of the Selectively Betainised Tertiary Amine Methacrylate Block Copolymers Finally, the first examples of betainised-quaternised diblock copolymers were also synthesised from DMA-MEMA, DMA-DEA and DMA-DPA precursor block copolymers (Table 4.6). Selective betainisation of the DMA residues in each block copolymer was achieved using 1,3-propane sultone in THF (see Chapter 2). Subsequent quaternisation of the second block was carried out using MeI in alkaline aqueous medium (pH>8) in which the second blocks are deprotonated. Calculated molecular weights and reaction conditions are listed in Table 4.6.

Table 4.6 A summary of block copolymer compositions, precursor molecular weights, and calculated molecular weights of selectively betainised and quaternised block copolymers. Sample code

Polymer

DMA content (mol%)a

Precursor Mn b (gmol-1)

Calcd. Mnc Solvent for Solvent and pH After betn. betainisationd for quaternisation and quatn.

VB134 betDMA-meDEA

51

32,600

57,400

THF

water/pH 7-8 e

VB146 betDMA-meDPA

72

12,050

25,300

THF

water/pH 7-8 f

VB145 betDMA-meMEMA

46

25,500

44,300

THF

water/pH 7-8 e

a: As determined by 1H NMR spectroscopy b: As determined by GPC (calibrated with poly(methyl methacrylate) standards) c: As calculated from GPC analyses of precursor polymers d: at 20oC for 24h e: at 20oC for 24h f: at 45oC for 48h

Figure 4.12 shows the 1H NMR spectrum of the betainised-DMA-quaternised-DEA copolymer, before and after quaternisation of the DEA residues, which indicates the successful quaternisation of DEA residues in the selectively betainised DMA-DEA block copolymer (compare spectra a and b). The peak K corresponds to the methyl group bound to the nitrogen of the DEA residues after quaternisation. In addition, the DEA protons (such as -CH2 bound to nitrogen) are shifted downfield to δ 3.5 and δ 3.7-3.8 after quaternisation. Peak integral analysis of the C, K and J peaks indicated a degree of

139


quaternisation 100%. Similar spectra were obtained with the betainised-quaternised DMA-DPA and DMA-MEMA block copolymers. CH 3

CH 3

( CH2

)

C C

( CH2

0.51 O

C H3C

A)

O

CH2 A

CH2 G

D CH3 C

N

CH2 H _ Cl N+

CH 2 D

I H2C

CH 2 I

CH 2 E

J H 3C

CH 3 J

CH 2 F _ SO3

(

CH 2

CH 3

C

) 0.51

C

O

( CH 2

K I D

4 .5

4 .0

3 .5

O

J

CH 2 A

CH 2 G

+

N

K H 3C

CH 3 C

CH 2 H _ I N+

CH 2 D

I H 2C

CH 2 I

CH 2 E

J H 3C

CH 3 J

CH 2 F _ SO3

F

E

B+H

A+G

) 0.49

C O

CH 2 B C H 3C

C

O

C

5 .0

0.49 O

O

CH 3

B)

)

C

CH2 B +

C

3 .0

2 .5

2 .0

1 .5

1 .0

δ /p p m

Figure 4.12 1H NMR spectra of both (A) a selectively betainised DMA-DEA precursor copolymer and (B) after quaternisation of the DEA block with MeI (betainised DMA-quaternised DEA block copolymer) containing 51 mol % DMA in D2O (precursor Mn = 32,600 g mol-1; VB134).

These betainised-quaternised blocks were expected to undergo salt-induced micellisation, with the betainised (salt-liking) block forming the solvated corona in each case. However, no micellisation was observed even at salt concentrations of up to 4 M KCl as judged by

140


PCS and 1H NMR spectroscopy. Further studies on the aqueous solution behaviour of these new copolymers will be carried out in the near future. 4.5 CONCLUSIONS A series of tertiary amine methacrylate homopolymers and new dibasic block copolymers have been synthesized using GTP. The block copolymers can be molecularly dissolved in aqueous solution without using a co-solvent. They exhibit reversible pH-, salt- or temperature-induced micellisation and are remarkably surface active at around neutral pH. It is difficult to obtain stable micelles with the block copolymers at high temperature and at high pH due to decreased solubility of the DMA residues. Thus, the DMA residues in the DMA-DEA, DMA-DPA and DMA-MEMA block copolymers were selectively quaternised using both methyl iodide and benzyl chloride in order to increase the solubility of the DMA block.

It is difficult to get stable DMA MEMA block copolymer micelles with either DMA or MEMA block forming micelle core due to small temperature differences (5-10oC) between the clouds points of these two blocks. As mentioned in Chapter 2, Although partial protonation of the DMA residues produced much greater solubility differences between the two blocks, the micelles, the MEMA core, were not stable in a widetemperature range (2-4oC). However, selective quaternisation of the DMA residues produced much greater solubility differences between the blocks, thus the MEMA block became insoluble and formed micelle cores at high temperature. Similarly, selectively quaternised DMA-DEA and DMA-DPA block copolymers both exhibited pH-induced micellisation and formed stable micelles at high pH as expected. Quaternisation significantly reduced the surface activities of the DMA-DEA precursor block copolymers. PCS indicated intensity-average micelle diameters of 14-40 nm. In some cases relatively monodisperse micelles were obtained. 1H NMR spectroscopy studies confirmed that the quaternised DMA residues formed the micelle corona in each case, with the micellar cores comprising MEMA, DEA or DPA residues, respectively. Micellisation was completely reversible in all cases. Finally, selectively betainised DMA-quaternised DEA (or DPA or MEMA) polyelectrolytes were also obtained from the same tertiary amine methacrylate precursor copolymers. Micellisation behaviour and surface activity of all

141


these block copolymers were investigated using 1H NMR spectroscopy, PCS and surface tensiometry.

4.6 REFERENCES

1.

D.J. Liaw, S.J. Shiau and K.R. Lee, J. Appl. Polym. Sci., 45, 61, 1992.

2.

W.F. Lee and G.Y. Huang, J. Appl. Polym. Sci., 60, 187, 1996.

3.

N. Nugay, Z. Kucukyavuz and S. Kucukyavuz, Polym. Int., 32, 93, 1996.

4.

K. Deboudt, M. Delporte and C. Loucheux, Macromol. Chem. Phys., 196, 279, 1995.

5.


6.


7.

M. Pradny and S. Sevcik, Macromol. Chem., 188, 2875, 1987.

8.


9.

K. Nagai, Trends Polym. Sci., 4(4), 122, 1996.

10. K. Nagai, I. Fujii and N. Kuramoto, Polymer, 33(14), 3060, 1992. 11. K. Nagai, Y. Ohishi, H. Inaba and S. Kudo, J. Polym. Sci.: Part A: Polym. Chem., 23, 1221, 1985. 12. K. Nagai and Y. Ohishi, J. Polym. Sci.: Part A: Polym. Chem., 32, 445, 1994. 13. K. Nagai and Y. Ohishi, J. Polym. Sci.: Part A: Polym. Chem., 25, 1, 1987. 14. K. Nagai, Macromol. Symp., 84, 29, 1994. 15. K. Nagai, Y. Ohishi, K. Ishiyama and N. Kuramoto, J. Appl. Polym. Sci., 38, 2183, 1989. 16. J. Selb and Y. Gallot, Makromol. Chem., 181, 809, 1980. 17. J. Selb and Y. Gallot, Makromol. Chem., 181, 2605, 1980. 18. J. Selb and Y. Gallot, Makromol. Chem., 182, 1491, 1981. 19. J. Zhu, A. Eisenberg and R. B. Lennox, Macromolecules, 25, 6556, 1992. 20. J. Zhu, A. Eisenberg and R. B. Lennox, J. Am. Chem. Soc., 113, 5583, 1991. 21. K. Ishizu, Y. Kashi, T. Fukutomi and T. Kakurai, Makromol. Chem., 183, 3099, 1982. 22. E.A Boucher and R. Khosravi-Babadi, J. Chem. Soc., Faraday Trans. 1, 79, 1951, 1983.

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23. K. Ishizu, K. Inagaki and T. Fukutomi, J. Poly. Sci.: Polym. Chem. Ad., 23, 1099, 1985. 24. K. Ishizu, K. Bessho, T. Fukutomi and T. Kakurai, Makromol. Chem. Rapid Commun., 4, 163, 1983. 25. N. Nugay, C. Hosotte, T. Nugay and G. Riess, Eur. Polym. J. 30(10), 1187, 1984. 26. E. A. Lysenko, T. K. Bronich, A. Eisenberg, V. A. Kabanov and A. V. Kabanov, Macromolecules, 31, 4516, 1998. 27. H.C. Brown and A. Cahn, J. Amer. Chem. Soc., 77, 1715, 1955. 28. C.C. Mollett, PhD Thesis, University of Sussex, Brighton, 1979. 29. C.L. Arcus and W. A. Hall, J. Chem. Soc. 2, 5995, 1964. 30. a) N. Menschutkin, Z. Physik. Chem. 5, 589, 1890. b) J. Chem. Soc. Abstr., 385, 1895. 31. D. Loveday and G. L. Wilkes, Pure Appl. Chem., A34(5), 807, 1997. 32. P. M. Pradny, J. Lokaj, M. Novatna and S. Sevcik, Makromol. Chem., 190, 2229, 1989. 33. M. Pradny and S. Sevcik, Makromol. Chem. 186, 1657, 1985. 34. Y. Yasuda, K. Rindo, R. Tsushima and S. Aoki, Makromol. Chem. 194, 1893, 1993. 35. L. Leemans, R. Jerome and Ph. Teyssie, Macromolecules, 31, 5565, 1998. 36. D. Hunkeler and A. E. Hamielec, Polymer, 32(14), 2626, 1991. 37. S. Creutz, P. Teyssie and R. Jerome, Macromolecules, 30, 6, 1997. 38. H.C. Brown, J. Chem. Soc. 1248, 1956. 39. H.C. Brown, J. Am. Chem. Soc., 67, 1452, 1945. 40. H.C. Brown, J. Am. Chem. Soc., 67, 378, 1945. 41. H.C. Brown, H. Bartholomay and Jr. and M.D. Taylor, J. Am. Chem. Soc., 66, 435, 1944

143

Chapter 5-SCK micelles

CHAPTER 5.

Synthesis and Characterisation of Tertiary Amine Methacrylate-Based Shell Cross-Linked Micelle

5.1 INTRODUCTION

143


There is increasing interest in the formation and characterization of block copolymer micelles in aqueous media. Various biomedical applications have been suggested1-5. In general, micellisation occurs above a certain critical micelle concentration (cmc) and generally depends on the solution pH,6 temperature7,8 and salt concentration. If any of these parameters is changed, the micelles may either dissociate back into the original unimers or form higher aggregates or precipitate from solution. These limitations can cause problems when stable micelles are required. Thus, many researchers have instead focused on the synthesis of dendrimers9,10. However, dendrimer synthesis is generally both costly and time-consuming. Cross-linked micelles can be obtained by cross-linking either the micelle core11-13 or the micelle corona.14-23 Core cross-linked micelles have been reported with sizes typically between 0.02-1 μm. These cross-linked micelles contain hydrophobic micellar shells which limit their use in biological applications.15 Thus, in recent years considerable research has been devoted to the cross-linking of micellar coronas in either aqueous solution or in organic solvents using various crosslinking chemistries such as esterification,16 amidation,16 irradiation,17-23 quaternisation etc. To date, all block copolymers used in the shell cross-linked micelle (SCK) synthesis have hydrophobic blocks (commonly polystyrene or polypyrene) which require the use of co-solvent and lead to permanently hydrophobic cores.

In a recent series of papers Wooley and co-workers reported the synthesis of shell crosslinked ‘knedel’ (SCK) micelles.14-22 According to the authors, these novel supramolecular structures appear to be a hybrid between dendrimers, hollow spheres, latex particles, and block copolymer micelles.’ A broad range of applications, in areas as diverse as solubilization, catalysis, fillers, coatings and delivery, has been suggested for these fascinating new materials.17 Wooley’s group reported several synthetic routes to SCK micelles.

In

their

original

communication

poly(styrene-block-4-vinylpyridine)

copolymers were first partially quaternised with 4-chloromethylstyrene and then crosslinked via UV irradiation at 254 nm in the presence of 4,4’-azobis(4-cyanovaleric acid) initiator.17 In later papers, both esterification and carbodiimide coupling chemistry were also used for the shell cross-linking of the solvated PAA corona of the PAA-PS16 and PAA-polyisoprene19 block copolymers using either 1,2-bis(2-bromoethoxy)ethane or a series of di- and multiamino linkers such as 2,2'-(ethylenedioxy)bis(ethylamine).16

144


Wooley’s group investigated the factors affecting the dimensions and properties of the SCK micelles such as degree of shell cross-linking, comonomer ratio in the precursor block copolymer and also the degree of quaternisation of the P4VP residues.18 The encapsulation of small hydrophobic molecules by these SCK micelles was also examined.15 Although the synthesis of SCK micelles is quite straightforward (indeed, rather attractive compared to multi-step dendrimer syntheses), two problems are apparent. Firstly, the shell cross-linking reaction must be carried out at relatively high dilution in order to avoid inter-micellar cross-linking. In addition, the SCK micelles cannot be normally re-dissolved in water after rigorous drying, although partial quaternisation with hydrophilic poly(ethylene oxide) derivatives apparently alleviates this problem.18 Moreover, all examples of SCK micelles described to date by Wooley and co-workers have only hydrophobic micellar cores, typically based on polystyrene or polyisoprene. If these ‘nanocapsules’ were to be used as delivery vehicles, an explicit release mechanism would be desirable. Ding and Liu23 synthesised SCK micelles using a polystyrene-poly(2-cinnamoylethyl methacrylate (PS-PCEMA) block copolymer with the PS forming the micelle core and the PCEMA forming the micelle corona in THF/acetonitrile solution. The PCEMA shell was cross-linked (or dimerised) by UV photolysis. The effect of the degree of CEMA conversion on the micellar diameter and the degree of intermicellar fusion was investigated. It was demonstrated that the micellar structure was locked in at a CEMA conversion of ~ 10%. The hydrodynamic diameter increased with CEMA conversion below ~11% conversion; at lower conversions the micelles were not fully cross-linked since dissolution occurred in THF. The micellar diameter reached a maximum at a CEMA conversion of 11%, which corresponds to the CEMA conversion where the micelles are just locked in. On the other hand, the degree of intermicellar fusion was found to be low for CEMA conversions lower than ~40%. These SCK micelles were not stable at higher CEMA conversions due to the reduced solubility of the PCEMA corona in THF/acetonitrile after extensive inter- and intra-chain CEMA dimerization. The hydrodynamic diameter increased up to 326 nm, indicating the formation of micellar aggregates. It was also reported that the micellar diameter increased from 32 to 62 nm at a CEMA conversion of 15% when the THF content of the solution was increased from 10% to 91%. This was reported to be due to swelling of both blocks. In addition, these SCK

145


micelles are stable in good solvents for PCEMA such as THF and toluene and can be easily redispersed after drying.

The same research group also reported the synthesis of "porous nanospheres" by crosslinking PCEMA residues in the micelle core of the poly[(2-cinnamoylethyl methacrylaterandom-(2-octanoylethyl methacrylate)-block-poly(acrylic acid)] copolymer micelles in aqueous solution.12,13 It was suggested that these water-soluble porous nanospheres might be particularly advantageous in controlled drug release, because the internal voids should allow higher drug loadings. However, after drying these SCK micelles have poor waterdispersibility similar to Wooley’s SCK micelles.

All shell cross-linked micelles mentioned above contain a hydrophobic block in the micelle core. These SCK micelles, such as PS-MAA, PS-P4VP, were very difficult to redisperse in water after drying. In addition, the hydrophobic micelle cores of these SCK micelles limit their potential biomedical applications (due to the difficulties in controlling the diffusion of the materials from the micelle core to the solvent) such as drug delivery, encapsulation, gene therapy etc.

Here in, we report the synthesis of novel SCK micelles of 20-40 nm diameter by reacting a series of tertiary amine methacrylate (co)polymers, namely DMA-MEMA, DMA-DEA and DMA-DPA, with a bifunctional quaternising agent, 1,2-bis-(2-iodoethoxy)ethane (BIEE), in aqueous solution. These new SCK micelles differ from those reported by Wooley’s group in that the micelle core can be reversibly hydrated or dehydrated depending on the solution temperature and/or electrolyte concentration. The ability to control the degree of hydration of the micelle cores suggests possible uptake/release applications.

In addition, we describe the synthesis of new zwitterionic SCK micelles of 20-60 nm diameter. These zwitterionic SCK micelles were synthesised by shell cross-linking either a 2-(dimethylamino)ethyl methacrylate-tetrahydropyranyl methacrylate (DMA-THPMA) diblock copolymer or a zwitterionic 2-(dimethylamino)ethyl methacrylate-methacrylic acid block copolymer (DMA-MAA) with BIEE in aqueous solution. Depending on the synthetic route, the DMA block can form either the shell cross-linked corona or the

146


micelle core. These new “nanoparticles” have interesting aqueous solution properties such as well-defined isoelectric points. Both types of SCK micelles (DMA core and MAA core) were extensively characterized using NMR and FTIR spectroscopy, PCS, TEM and zeta potential measurements. Two short communications reporting our preliminary results for the shell cross-linked partially quaternised DMA-MEMA block copolymer micelles24 and zwitterionic shell cross-linked micelles25 have been published in J. Am. Chem. Soc.

5.2 EXPERIMENTAL

5.2.1 TERTIARY AMINE METHACRYLATE COPOLYMER SYNTHESIS

5.2.1.1 The Synthesis of Precursor Block Copolymers: Each series of the DMAMEMA, DMA-DEA and DMA-DPA diblock copolymer was synthesized using group transfer polymerisation as described in Section 2.2.4. The DMA monomer was polymerized first in each case and quantitative yields were obtained for all monomers. The Mn’s of the precursor block copolymers, as measured by gel permeation chromatography are summarised in Table 5.1. The DMA content of the block copolymer was determined by proton NMR spectroscopy in either D2O or CDCl3.

5.2.1.2 Partial Quaternisation: Partial selective quaternisation of the DMA residues in both the DMA-MEMA and the DMA-DEA block copolymers was achieved using methyl iodide in THF (25oC for 2 h). This partial quaternisation allows us to control the degree of shell cross-linking and to increase the solubility of the DMA residues. The partial degrees of quaternisation and the calculated molecular weights are also summarised in Table 5.1.

5.2.1.3 DMA-MEMA Block Copolymer Micelles: A 48:52 DMA-MEMA block copolymer (0.3-0.5 g) was dissolved in water (100 ml) and the solution pH was adjusted to 7.5. This copolymer is completely soluble as unimers at pH 7.5 and room temperature. Micelles with the MEMA block in the core were then obtained by the addition of sufficient solid Na2SO4 to achieve a 1 M solution prior to shell cross-linking. At high salt concentration, the MEMA block becomes dehydrated and is ‘salted out’ as described in Section 2.4.2 and Section 2.4.4.3. This is confirmed by proton NMR studies: proton signals due to the MEMA block are significantly reduced in intensity relative to the DMA

147


signals. In addition, shell cross-linking of the DMA-MEMA block copolymer was also carried out at high temperature (55-60oC) in the presence of low salt concentration (0.1 M Na2SO4).

5.2.1.4 Partially Quaternised DMA-MEMA Micelles: A 0.50 wt. % aqueous solution of the partially quaternised DMA-MEMA block copolymer in 0.10 M Na2SO4 at pH 10 was heated to 60oC (see Table 5.1). Under these conditions the MEMA block becomes dehydrated and forms the non-solvated micelle core, with the partially quaternised DMA block forming the solvated corona as described in Section 2.4.4.3. In addition, micelles of the same copolymer were obtained at room temperature by increasing the salt concentration up to 0.5-1.0 M Na2SO4. Temperature-induced micellisation was confirmed by variable temperature proton NMR studies and PCS studies at 60oC. The intensityaverage micelle diameter was ca. 36 nm. The micelle diameters are summarised in Table 5.1.

5.2.1.5 DMA-DEA and DMA-DPA Micelles: The DMA-DEA block copolymer (0.150.4 g) was first dissolved in water (100 ml) as unimers at pH 2 and the solution pH was then increased above the critical micellisation pH using KOH at room temperature. The hydrodynamic micelle diameters were summarised in Table 5.1, as measured using PCS. The same procedure was used to prepare micellar solutions with the DMA-DPA block copolymer and the partially quaternised DMA-DEA copolymer at room temperature.

5.2.1.6 Shell Cross-Linking of the Block Copolymer: In all SCK syntheses, the target degree of shell cross-linking of the DMA corona was chosen to be between 40-50 mol %. This was achieved by adding BIEE to the micellar solutions mentioned above. The solution was stirred for at least 2-4 days. The resulting SCK micelles were characterized using NMR, PCS and TEM and the results are summarised in Table 5.1.

5.2.2 ZWITTERIONIC SCK SYNTHESES

148


5.2.2.1 Polymer Synthesis and Characterization: A series of the precursor DMATHPMA block copolymers was prepared by Dr. A. B. Lowe (a former member of the Sussex Polymer Group) using GTP. Synthetic details have been published in full elsewhere26-28 and are only briefly summarised here. The DMA monomer was polymerised first and quantitative yields were obtained for both monomers. Copolymers of differing compositions were produced by varying the DMA content from 43 to 82 mol % (Table 1). Copolymer compositions were determined using 1H NMR spectroscopy by comparing the peak integrals of the two methylene protons bound to the DMA ester group at δ 4.1 (or the two methylene protons bound to nitrogen at δ 2.6) with the single tetrahydropyranyl proton of the THPMA at δ 5.9 in CDCl3 (not shown)27. The molecular weights were determined by GPC and are summarised in Table 5.2. The molecular weight of the zwitterionic DMA-MAA block copolymer was calculated assuming 100 % deprotection of the THP groups.

5.2.2.2 Deprotection of the THPMA Residues: Removal of the THP groups in the DMA-THPMA block copolymers was carried out via acid hydrolysis. Concentrated HCl (3 ml) was added to the DMA-THPMA block copolymer (3 g) dissolved in H2O (100 ml) and the solution was then stirred at room temperature for 2 days. The resulting zwitterionic DMA-MAA block copolymer (Type II) was precipitated at its isoelectric point (IEP) by adding KOH solution (0.5 M). It was washed with deionised water (whose pH was equal to the IEP, see Table 5.2) and dried in a vacuum oven at 50oC for 24 h. 1H NMR spectroscopy and FTIR spectroscopy studies confirmed that complete deprotection had been achieved. The same general procedure was used for deprotection of the THPMA cores of the shell cross-linked DMA-THPMA micelles.

5.2.2.3 ‘Type I’ Micelle Formation: The hydrophilic-hydrophobic DMA-THPMA block copolymer (0.20-0.25 g), was dissolved in 5 ml THF, which is a good solvent for both blocks. Deionised water (95 ml) was then slowly added with continuous stirring. The micellar solution (with the hydrophilic DMA block forming the solvated corona and the hydrophobic THPMA block forming the micelle core) was equilibrated at room temperature for 60 minutes before shell cross-linking. The precursor micelle size was between 20-24 nm as measured by PCS (see Table 5.3). The final shell cross-linked micelles were termed “Type I micelles”.

149


5.2.2.4 ‘Type II’ Micelle Formation: The zwitterionic 43:57 DMA-MAA block copolymer (0.23-0.24 g), was dissolved in deionised water (100 ml) and the solution pH was adjusted to pH 10 using KOH (0.5 M). This zwitterionic block copolymer undergoes reversible micellisation (with the DMA block forming the micelle core and the MAA block forming the solvated corona) in alkaline media as the solution temperature is raised above the cloud point of the DMA block.26 The intensity-average micelle diameter was approximately 56 nm as measured by PCS using the CONTIN algorithm. In some experiments, electrolyte was added to the micellar solution to achieve narrower micelle size distributions. The final shell cross-linked micelles were termed “Type II micelles”.

5.2.2.5 Cross-Linking and Deprotection of the DMA-THPMA Block Copolymer:

5.2.2.5.1 Route I: In order to prepare SCK micelles by selective cross-linking of the solvated DMA residues in the Type I micelles, BIEE (30-50 μl) was added to the solution under nitrogen and stirred at room temperature for 4 days. The resulting SCK micelles were characterized using NMR spectroscopy, FTIR spectroscopy, PCS and zeta potential measurements prior to removal of the THP groups in the hydrophobic THPMA micelle cores.

5.2.2.5.2 Deprotection of the THPMA Residues in the SCK Micelles: HCl solution (3 M, 3 ml) was added to the above SCK micelles and the aqueous solution was stirred for 3 days at room temperature. After neutralization of the excess HCl by addition of KOH, the deprotected zwitterionic micelle, Type I, was either precipitated at its IEP or dialyzed with de-ionised water. After washing with water, half of the SCK micelle solution was freeze-dried and the rest was redissolved either at pH 2 or at pH > 9. The SCK micelles were characterized by NMR spectroscopy, FTIR spectroscopy, PCS and zeta potential measurements. For the NMR measurements, the SCK micelles were precipitated at their IEP, washed with D2O three times and redissolved in D2O at a pH either lower or higher than the IEP. The solution pH was adjusted using DCl and NaOD solutions (0.1-1.0 M).

5.2.2.5.3 Route II: In order to shell cross-link the MAA residues in the Type II micelles, the same BIEE cross-linking agent (30-40 μl) was added to the micellar solution under

150


nitrogen at 60oC and stirred for 2 h. Actually, PCS studies suggested that cross-linking of the MAA residues was complete within 20-30 min. The resulting SCK micelles were also characterized using NMR and FTIR spectroscopy and zeta potential measurements.

5.2.3 CHARACTERIZATION

5.2.3.1 Gel Permeation Chromatography (GPC): The molecular weights (Mn) and the polydispersities (Mw/Mn) of the DMA-DEA, DMA-DPA, DMA-MEMA and DMATHPMA precursor copolymers were determined by using GPC. The non-aqueous GPC set-up comprised a Perkin Elmer LC pump, an RI detector, and a PLgel 3 μm Mixed 'E' column (PMMA standards, THF eluent, flow rate 1.0 ml min-1). 1

5.2.3.2 H NMR Spectroscopy: Block copolymer compositions were determined by proton NMR spectroscopy in either D2O or CDCl3. All 1H NMR spectra of the SCK micelles and the precursor block copolymers were recorded using either a Bruker 250 or 300 MHz instrument. In certain experiments the solution pH was adjusted using DCl or NaOD as required. D2O was used as the solvent for all SCK micelles and hydrophilichydrophilic block copolymers, while CDCl3 was used for the DMA-THPMA precursor block copolymer.

5.2.3.3 Zeta Potential Measurements: Zeta potential measurements of the zwitterionic SCK micelles were carried out to determine the particle surface charge using a Malvern Zetamaster instrument. Zeta potentials of 0.02 % (w/v) copolymer solutions were determined for the SCK micelles both before and after deprotection by adjusting the pH from 2 to 12 using 0.1 M HCl or KOH.

5.2.3.4 FTIR Spectroscopy: All FTIR spectra were recorded on the dried zwitterionic SCK micelles using a Nicolet Magna 550 Series II instrument with a golden gate ATR accessory. Deprotection of the DMA-THPMA block copolymer in both its precursor and SCK micelle form was confirmed.

151


5.2.3.5 Dynamic Light Scattering (DLS): See Section 2.3.5 for the experimental o

o

conditions. All measurements were made between 25 C and 60 C on 0.2 to 0.5 wt. % copolymer solutions at a fixed angle of 90o. 5.2.3.6 Transmission Electron Microscopy (TEM): Dilute (< 0.1 %) suspensions of the SCK micelles were dried onto a TEM grid and examined using an Hitachi 7100 instrument without any staining. 5.3 RESULTS AND DISCUSSION 5.3.1 Partially Quaternised DMA-MEMA Shell Cross-Linked Micelles 5.3.1.1 Verification of the SCK Micelle Structure: Proton NMR spectroscopy indicated a degree of quaternisation of 30 % for the DMA residues in both the 35:65 and 40:60 DMA-MEMA block copolymers (see Table 5.1). Control experiments with DMA and MEMA homopolymers confirmed that the MEMA block is not quaternised under these reaction conditions (see Section 4.4.1). This quaternisation step allows sufficient discrimination between the hydrophilic DMA and MEMA blocks in aqueous media, since the partially quaternised DMA block no longer exhibits inverse temperature-solubility behaviour. Thus, this derivatized block copolymer undergoes reversible micellisation in aqueous media (with the MEMA block forming the hydrophobic micelle core and the partially quaternised DMA block forming the solvated corona) on raising the solution temperature above the cloud point of the MEMA block (see Figure 5.1a). A 0.50 wt. % aqueous solution of the partially quaternised DMA-MEMA block copolymer in 0.10 M Na2SO4 at pH 10 was heated to 60oC. Under these conditions the MEMA block becomes dehydrated and forms the nonsolvated micelle cores.

152


A) DMA-MEMA SCK synthesis

pH 7-8, 50-60oC

DMA-DEA or Partially quaternized DMA-MEMA block copolymer

DMA-DEA/DMA-DPA diblock copolymer

Reversible micellisation in the presence of 1 M Na2SO4 at 25oC or 50oC without salt

M I C E L L E

Irreversible shell cross-linking via BIEE

+ +

+ +

+

Cool to 25 C

+

+

+ +

+ + +

+ + +

+

+ +

+

+

+ S C K

+

+

S C K

+

+

+ +

o

+

+

+ +

+

+ + +

+

+ +

+ + +

+ +

+

+ + +

+ + +

+

+

+

Hydrophobic micelle core

Hydrophilic micelle

B) DMA-DEA and DMA-DPA SCK synthesis Reversible micellisation at pH > 8 M I C E L L E

Partial quaternization with MeI

+ +

Irreversible shell cross-linking via BIEE at 25oC

Reversible micellisation at pH > 8

+

+ +

+ +

+

S C K

+

+ +

+

+

+ +

+ +

+ +

+ + +

+ + +

Partially quaternized DMA-DEA or DMA-DPA unimers

+

+ +

+

pH < 6 +

+ + +

+ +

Hydrophobic micelle core with DMA-DEA, DMA-DPA and partially quaternised derivatives

pH > 7

S C K

+

+ +

+ +

+ + +

+ + +

+ +

+

+

+ + +

+ +

Hydrophilic micelle core with partially quaternised DMA-DEA copolymer

Figure 5.1 Reaction scheme for the synthesis of tertiary amine methacrylate-based SCK micelles with or without partial quaternisation. 153


Table 5.1 A summary of the molecular weights, the degrees of quaternisation, solution conditions and hydrodynamic diameters of the precursor block copolymers (DMA-MEMA, DMA-DEA and DMA-DPA) and their SCK micelles DMA Degree of Precursor Content quaternisation Mnb a a (mol%) (mol%) (gmol-1)

Temp. (oC)

pH

Precursor Micelle Diameterc (nm)

SCK Micelle diameterc (nm)

18,400 18,400

25 25

7-8 2/10

34 ---

38 49/38

44 44

35,000 35,000

25 25

10 2

38 unimer

38 46

72 72

0 0

11,800 11,800

25 25

7 2

21 unimer

26 38

DMA-MEMA DMA-MEMA DMA-MEMA DMA-MEMA

35 35 35 35

30 30 30 30

36,000 36,000 36,000 36,000

25 60 60 25

7-8/2 7-8 2 7-8

unimer 36 unimer unimer

---28 38 30

VB196 VB196 VB196

DMA-MEMA DMA-MEMA DMA-MEMA

48 48 48

0 0 0

21,500 21,500 21,500

55 25 25

7-8 7-8 10/2

23 unimer --

20 21 21/25

VB208 VB208 VB208

DMA-MEMA DMA-MEMA DMA-MEMA

40 40 40

30 30 30

27,600 27,600 27,600

65 25 25

10 10 2

22 unimer unimer

23 28 29

Sample Code

Block Copolymer

VB177 VB177

DMA-DEA DMA-DEA

50 50

0 0

VB204 VB204

DMA-DEA DMA-DEA

50 50

VB180 VB180

DMA-DPA DMA-DPA

VB170 VB170 VB170 VB170

a) As determined by 1H NMR spectroscopy. Quaternised using MeI.

b) As determined by GPC c) As determined by PCS spectroscopy This micellisation is confirmed by variable temperature proton NMR studies: proton signals due to the MEMA block were significantly reduced in intensity relative to the DMA signals at 60oC (compare ‘spectrum a’ and ‘spectrum b’ in Figure 5.2). Dynamic light scattering studies at 60oC indicated an intensity-average micelle diameter of 36 nm (see Table 5.1). Shell cross-linking of the unquaternised DMA residues was achieved by adding BIEE (0.40 mol per mole of the DMA residues) to the micellar solution at 60oC. At 60oC the intensity-average micelle diameter during the shell cross-linking reaction was 28 nm. However, after cooling this reaction solution to 25oC, dynamic light scattering studies indicated an intensity-average diameter of ca. 30 nm, which confirms the formation of SCK micelles. If shell cross-linking had been unsuccessful no micelles could exist at room temperature since, under these conditions, the MEMA block is hydrophilic and there would be no reason for the block copolymer chains to remain aggregated. The slight increase in micelle diameter on cooling from 60oC to 25oC indicates a small degree

154


of swelling due to the ingress of water into the now-hydrophilic MEMA core. A proton NMR spectrum of these SCK micelles recorded in D2O at 60oC and 0.25 M Na2SO4 indicated that shell cross-linking was incomplete since there is a residual signal due to the unquaternised DMA residues at δ 2.2-2.3 (see Figure 5.2c). Comparison of this peak integral with that due to the quaternised DMA residues at δ 3.1-3.3 indicated that around 30% of the DMA residues remained unquaternised after shell cross-linking. Taking into account the original degree of quaternisation of 30 % obtained using methyl iodide, we estimate an upper limit of 14 % for the degree of shell cross-linking of the block copolymer. However, the actual degree of shell cross-linking is most likely somewhat lower, since a significant proportion of the -CH2I groups of the bifunctional cross-linking agent probably remains unreacted, and also some degree of intrachain reaction is likely.

5.3.1.2 Dynamic Light Scattering Studies: Although the effect of temperature on the SCK micelle diameter described above is relatively small, it was found to be both reproducible and fully reversible. Significantly larger changes in micelle diameter were observed on varying the solution pH. Thus, micelles of 30 nm at 25oC and pH 10 swelled up to 38 nm at pH 2 on addition of HCl (see Table 1). This is presumably due to extensive protonation of the MEMA core. Such pH-induced micelle swelling is reversible: returning to pH 10 by addition of NaOH produced micelles of 31 nm. Finally, heating an acidic (pH 2) micellar solution from 25oC to 60oC apparently leads to micelle de-swelling, since the intensity-average micelle diameter decreases from 38 nm to 32 nm. This is a surprising observation since the noncross-linked, partially quaternised DMA-MEMA block copolymer remains completely soluble as unimers under the same conditions, which suggests that temperature-induced dehydration of the MEMA block does not occur at pH 2. Thus, we have no satisfactory explanation for micelle deswelling at elevated temperature in acidic solution.

5.3.1.3 Proton NMR Spectroscopy Studies: Variable temperature NMR spectra recorded for the partially quaternised DMA-MEMA block copolymer in D2O (pH 10, 0.25 M Na2SO4) are shown in Figure 5.2. At 25oC NMR signals due to both the DMA block (at δ 3.1-3.3) and MEMA block (at δ 3.6-3.9 and δ 2.5-2.7) are observed, as expected (see Figure 5.2a).

155


CH 3

[(

CH 2

) 0.10

C C

a

H3C _

I

CH 3

( CH 2

C

O

CH 3

) 0.25 ]

C

[(

CH 2

O

C

) 0.65 ]

C

O

O

O

O

CH 2

CH 2

CH 2

CH 2

CH 2

+

N

CH 3

a

c

CH 2

N

c

N

CH 3

H 3C

CH 3

a

b

b

d

H2C

CH 2

d

e

H 2C

CH 2

e

O

e

d a

b

c

Partially quaternized DMA-MEMA block copolymer at 25 o C

No d

A

Block copolymer micelles at 60 o C prior to cross-linking

B

SCK micelles at 60oC

C

SCK micelles at 25oC

4.0

3.5

3.0

2.5

2.0

1.5

D

1.0

δ/ppm Figure 5.2 Variable temperature proton NMR studies of a 1.0 % D2O solution of a partially quaternised DMA-MEMA block copolymer (35 mol % DMA, Mn 36,000, 30 % quaternised MeI) at pH 10: (a) unimers at 25oC, (b) micelles at 60oC in the presence of 0.10 M Na2SO4; (c) shell cross-linked micelles at o 60 C in the presence of 0.25 M Na2SO4; (d) SCK micelles on cooling to 25oC in the presence of 0.25 M Na2SO4.

156


FUTURE WORK TA ELE ALABILIRSIN BURADA GEREKSIZ In future work, the effect of varying both the degree of quaternisation and the degree of cross-linking of the DMA corona on the redissolution of the SCK micelles will be studied systematically. In addition, the effect of the water miscible solvent on the swelling or hydration of the DEA core will be examined by varying solvent ratio such as water/THF (from 99:1 to 95:5)..

In future, it will be studied to increase solubility of the DMA-DEA and DMA-DPA SCK micelles and visibility of the micelle core by NMR after protonation and hydration.

157


170 198

ftir KISMINDAN Before deprotection, the copolymer spectrum had strong band due to the ester carbonyl bond at 17451722 cm-1. After deprotection the appearance of a new peak at 1555 cm-1 indicated carboxylate anion formation, which is consistent with the successful deprotection of the MAA residues in both precursor block copolymer and the SCK micelles.DELETE or AD TO RESULTS

158


M E M A residues

U nquaternized dimethylamino pro to ns o f D M A residues

N

d

H2 C

CH2

d

e

H 2C

CH2

e

N H 3C

O

e

CH 3

d

30 % quaternized D M A-M E M A P recurso r blo ck

A

B

SCK micelles

SCK micelles in 1.0 M Na2SO4

4.0

3.5

3.0

2.5

2.0

1.5

C

1.0

δ/ppm

Figure 5.3 Proton NMR studies of the effect of salt on partially quaternised SCK micelles at 25oC: (a) DMA-MEMA precursor block copolymer (35 mol % DMA, Mn 36,000, 30 % quaternised using MeI) in D2O at pH 10; (b) SCK micelles in D2O at 25oC, (c) SCK micelles in the presence of 1.0 M Na2SO4 at 25oC. Note the marked suppression of the MEMA signals in the micellar core as this block becomes dehydrated in the presence of salt. On heating this solution to 60oC the MEMA signals are reduced in intensity relative to the DMA signal (see Figure 5.2b). This indicates that the MEMA block becomes much less solvated under these conditions, which is consistent with dehydration of the micelle core. A similar NMR spectrum was obtained after shell cross-linking although, since the overall degree of quaternisation is now higher, the signal at δ 3.2 due to the three methyl groups of the quaternised DMA residues is increased (see Figure 5.2c).On cooling to 25oC, the MEMA signals regain their original intensities; this confirms rehydration of the

157


MEMA micelle cores (see Figure 5.2d). Temperature cycling confirmed that core (de)hydration was reversible. The effect of adding electrolyte (Na2SO4) at 25oC and pH 10 was also demonstrated for these SCK micelles (see Figure 5.3). Under these conditions the NMR signals due to the MEMA block are substantially suppressed, indicating a lower degree of hydration of the micellar core at high salt concentration (compare Figures 5.3b and 5.3c). Again, this effect is reversible: removal of the salt via dialysis restores the MEMA signals in the NMR spectrum.

Figure 5.4 Transmission electron micrograph of the SCK micelles prepared using a 30% quaternised 35:65 DMA-MEMA block copolymer.

5.3.1.4 Transmission Electron Microscopy Studies: A representative electron micrograph is shown in Figure 5.4. This confirms the reasonably narrow size distribution and spherical morphology of the SCK micelles and suggests a number-average micelle diameter of approximately 20 nm. Allowing for dehydration and polydispersity effects, this value is in reasonable agreement with the intensity-average diameter obtained from PCS measurements. 5.3.1.5 Redissolution of the Dried SCK Micelles: The partially quaternised SCK micelles can be redissolved in water after drying. Dynamic light scattering measurements

158


indicated only a modest increase in intensity-average micelle diameter, from 23 nm for the as-made SCK micelles up to ca. 30-40 nm for the redissolved micelles. This apparent increase in size most likely indicates some small degree of aggregation of the micelles, rather than a genuine increase in particle size.

5.3.2 DMA-MEMA Shell Cross-Linked Micelles (Without Partial Quaternisation)

The MEMA block’s low tolerance to added electrolyte also allows the preparation of SCK micelles without partial quaternisation of the DMA-MEMA precursor block. Because of their differing pKa’s (see Section 2.4.2), sufficient discrimination between the DMA and MEMA blocks can be achieved simply by careful control of the solution pH and the electrolyte concentration. Thus, a 0.4 % aqueous solution of the unquaternised DMA-MEMA block copolymer (48 mol % DMA; overall block copolymer Mn, 21,500) in 0.3 M Na2SO4 at pH 7.5 was heated to 55oC.

Variable temperature NMR studies (see Figure 5.5) confirmed that, under these conditions, the MEMA block forms the non-solvated micellar core, with the partially protonated DMA block forming the solvated corona. Dynamic light scattering studies at 55oC indicated an intensity-average micelle diameter of ca. 23 nm (Table 5.1). Successful shell cross-linking of the DMA residues was achieved by adding BIEE to this micellar block copolymer solution at 55oC. After cross-linking, the micelle diameter of the SCK micelle was 20 nm, as determined by PCS. As the solution cooled down to 25oC, the micelle diameter was almost unchanged (21 nm). Although the temperature dependence of the SCK micelle diameter is very small, significantly larger changes in micelle diameter were observed on varying the solution pH. Thus, micelles of 21 nm at 25oC and pH 10 swelled up to 25 nm at pH 2 on addition of HCl. This is presumably due to extensive protonation of the MEMA core. Such pH-induced micelle swelling is reversible: returning to pH 10 by addition of NaOH produces micelles of 21 nm. The effect of adding electrolyte (0.6 M Na2SO4) at 25oC and pH 10 was also demonstrated for these SCK micelles in Figure 5.5. Under these conditions the NMR signals due to the MEMA block at δ 3.6-3.9 and δ 2.5-2.7 are substantially suppressed, indicating a lower degree of hydration of the micellar core at high salt concentration

159


(compare spectrum b and spectrum c). Again, this effect is reversible: removal of the salt via dialysis restores the MEMA signals in the NMR spectrum (not shown). Thus, judicious selection of the aqueous solution conditions allows a more efficient synthesis of SCK micelles, since the quaternisation step may be omitted if desired.

MEMA residues

dimethylamino protons of DMA residues

N

d e

CH2

H2C

CH2

H2C

N

d

CH 3

H3C

e

O

e

d DMA-MEMA Precursor block copolymer

SCK micelles

SCK micelles in 0.6 M Na 2 SO 4

4.0

3.5

3.0

2.5

2.0

1.5

1.0

Figure 5.5 Proton NMR studies of the effect of salt on DMA-MEMA SCK micelles at ` 25oC: (a) DMA-MEMA precursor block copolymer (48 mol % DMA, Mn 21,500,) in D2O; (b) SCK micelles in D2O at 25oC, (c) SCK micelles in the presence of 0.6 M Na2SO4. Note the marked suppression of the MEMA signals in the micellar core as this block becomes dehydrated in the presence of salt. A representative electron micrograph of DMA-MEMA SCK micelle is shown in Figure 5.6. This confirms the reasonably narrow size distribution and spherical morphology of the SCK micelles and suggests a number-average micelle diameter of approximately 55

160


nm which is somehow larger than the hydrodynamic diameter of 20-30 nm determined by DLS.

Figure 5.6 Transmission electron micrograph of the SCK micelles prepared using a 48:52 DMA-MEMA block copolymer (without partial quaternisation). 5.3.3 DMA-DEA Shell Cross-Linked Micelles

A 0.16 % aqueous solution of the DMA-DEA block copolymer (50 mol % DMA; overall block copolymer Mn, 18,400) was prepared at pH 2 (as unimers) and the solution pH was then increased above the critical micellisation pH (pH 8.5) at 20oC to get a micellar solution (see Figure 5.1B). NMR studies confirmed that the DEA block forms the nonsolvated micellar core and the DMA block forms the solvated corona under these conditions. Dynamic light scattering studies at pH 8.5 and 20oC indicated an intensityaverage micelle diameter of 34 nm. The shell cross-linking of the DMA residues was achieved by adding BIEE to this micellar block copolymer solution. The micelle diameter of the SCK micelle was 38 nm, as determined by PCS. As the solution pH was lowered to 2, the SCK micelle diameter swelled from 38 nm to 49 nm. This is probably due to protonation of all the tertiary amine residues, as expected.

161


Partial quaternisation was also used to obtain micelles with more soluble DMA residues in alkaline media (between pH 8-13) prior to shell cross-linking of the DMA residues. Thus, after 44 % partial selective quaternisation of the DMA residues in a 50:50 DMA DEA block copolymer in water, this copolymer was first dissolved as unimers at pH 2 and a micellar solution was obtained at pH 10 by the addition of NaOH. Shell cross-linking at this pH (pH 10) was achieved using BIEE at room temperature (4 days). The initial micelle diameter was 38 nm and this did not change after shell cross-linking of the DMA residues. On the other hand, the micelle diameter was swelled up to 46 nm due to protonation of the amine residues, as the solution pH was lowered to 2 (see Table 5.1).

CH 3

CH 3

(

CH 2

C

) 0.50

C

O

( CH 2

C

) 0.50

C

O

O

O

CH 2 A

CH 2

D

CH 2 B _ Cl N+

H 3C C

CH 3 C

D

C

D

E _ Cl + N

F H 2C

CH 2 F

G H 3C

CH 3 G

B+E

G

CH 2

F

A+D

PRECURSOR

a) pH 2.0

PRECURSOR

b) pH 7.9

C

A

B

AFTER CROSS-LINKING

c) pH 2.0

d) pH 8.0

4.5

4.0

3.5

3.0

2.5

2.0

1.5

1.0

δ/ppm

Figure 5.7 Proton NMR studies of the effect of pH on both precursorcopolymer and its SCK micelles at 25oC; a 50:50 DMA-DEA precursor block copolymer a) at pH 2, b) at pH 7.9, c) after shell cross-linking at pH 8 and d) at pH 2.

162


Proton NMR studies confirmed that both the DMA and DEA blocks of the precursor DMA-DEA block copolymer are visible at pH 2 due to protonation of both tertiary amine residues (see Figure 5.7a). However, after cross-linking of the DMA corona of micelles formed by an unquaternised 50:50 DMA-DEA block copolymer, the DEA core is not visible under the same conditions (i.e. there is no hydration even at pH 2, see Figure 5.7b). This is probably due to the high degree of cross-linking of the DMA corona and relatively dehydrated nature of the DEA. With a partially quaternised DMA-DEA copolymer, the DEA core becomes partially hydrated at lower pH (pH < 4). After drying, attempted redissolution indicated differences between these two types of SCK micelles. Partial quaternisation of the DMA residues apparently aids redissolution of the dried SCK micelles. However, neither DMA-DEA SCK micelle was as easy to redissolve as the DMA-MEMA SCK micelles.

B

A

Figure 5.8 Transmission electron micrograph of the SCK micelles prepared using a 50:50 DMA-DEA block copolymer. (a) without quaternisation (VB166), (b) after partial (44 mol%) methylation of the DMA residues prior to shell crosslinking (VB204).

163


Representative electron micrographs are shown in Figure 5.8. This confirms the reasonably narrow size distributions and spherical morphology of both types of DMADEA SCK micelles (with or without partial quaternisation prior to cross-linking of the DMA cores) and suggests a number-average micelle diameter of approximately 60-80 nm for the 50:50 DMA-DEA SCK micelles and 20-30 nm for SCK micelles prepared using the same copolymer which had been 44% quaternised with MeI. Allowing for dehydration and polydispersity effects, these values are in reasonable agreement with the intensityaverage diameters obtained from PCS measurements (see Table 5.1).

5.3.4 DMA-DPA Shell Cross-Linked Micelles: For the synthesis of DMA-DPA SCK micelles; a 0.15 % aqueous solution of a DMA-DPA block copolymer (72 mol % DMA; overall block copolymer Mn, 11,800) was prepared at pH 7.8 and 20oC. Under these conditions, NMR studies confirmed that the DPA block forms the non-solvated micellar core, with the DMA block forming the solvated corona (see Section 2.4.4.2). Dynamic light scattering studies at pH 7.8 and 20oC indicated an intensity-average micelle diameter of 21 nm. Shell cross-linking of the DMA residues was achieved by adding BIEE to this micellar block copolymer solution. The micelle diameter of the SCK micelle was 26 nm, as determined by PCS. As the solution pH was lowered to pH 2, the SCK micelle diameter swelled from 26 nm to 38 nm due to protonation of either both types of tertiary amine residues or only uncross-linked DMA residues. After drying, these SCK micelles were less soluble than partially quaternised DMA-MEMA SCK micelles. This is probably due to the more hydrophobic DPA block. As can be seen in Figure 5.9, the DPA signals are not visible even at pH 2. This confirms that the DMA-DPA SCK micelles behave more like hydrophilichydrophobic SCK micelles i.e. similar to Wooley’s SCK micelles. Presumably, the DPA residues are not protonated at pH 2 due to high degree of cross-linking of the DMA corona. We believe that the DPA micelle core may become hydrated at lower pH by lowering the degree of shell cross-linking. This will be studied in the near future.

164


CH3

CH3 G

( CH2

C ) C

0.61 O

( CH2

C ) C

O

O

CH2 B + ClN

CH3

H3C Cl+ CH2 N

C H H

F

E D C H3C CH3 G

C

CH3

H3C

CH2 D

CH2 A D

0.39 O

G

C

A+D

F

B+E

pH 2

PRECURSOR

C

AFTER SCK

B

A

NO g

pH 7

C

NO g A

5.0

4.5

AFTER SCK

B

4.0

3.5

3.0

2.5

2.0

1.5

pH 2

1.0

δ/ppm

Figure 5.9 Proton NMR studies of the effect of pH on DMA-DPA SCK micelles at 25oC: Note the disappearance of the DPA signals (g and f) at pH 2 after shell crosslinking. Invisibility of the DPA signals at pH 2 after SCK suggests that the DPA residues either are not protonated even at pH 2 or are protonated but not visible due to the high degree of cross-linking of the DMA corona.

Representative electron micrographs are shown in Figures 5.10a and 5.10b. This confirms the reasonably narrow size distributions and spherical morphology of the DMA-DPA SCK micelles and suggests a number-average micelle diameter of approximately 20-50 nm. Allowing for dehydration and polydispersity effects, this value is in reasonable

165


agreement with the intensity-average diameter obtained from PCS measurements. The higher magnification image in Figure 5.10b shows clearly the core and the corona of the SCK micelle.

A

B

Figure 5.10 Transmission electron micrographs of the SCK micelles prepared using a 72:28 DMA-DPA block copolymer. 166


5.3.5 Zwitterionic SCK Micelles (Type I and Type II) The DMA-THPMA precursor block copolymer synthesised using GTP as shown in Figure 5.11 was used to prepare zwitterionic SCK micelles by shell cross-linking of either the DMA corona or the MAA corona. As shown schematically in Figure 5.12, two synthetic routes were utilised for the preparation of zwitterionic SCK micelles using the DMA-THPMA block copolymer precursors. In Route I, the block copolymer precursor was used for the preparation of SCK micelles. THF was used as co-solvent to initially dissolve the DMA-THPMA block as unimers. This solution was then diluted with water to a final composition of 95:5 v/v% water:THF. Under these conditions micellisation occurs, with the hydrophobic THPMA block forming the micelle core and the hydrophilic DMA block forming the micelle corona. Shell cross-linking by quaternisation of the DMA residues was followed by deprotection of the THPMA residues in the micelle core. In all SCK syntheses, relatively high degree of shell cross-linking (40-60 mol %) were sought in order to ensure that stable zwitterionic SCK micelles were obtained. The resulting SCK micelles have zwitterionic character: the MAA core is anionic and the DMA corona is cationic. Purification of these zwitterionic SCK micelles was achieved by precipitation at its IEP. In Route II (see Figure 5.12), the DMA-THPMA precursor block was first converted to the corresponding DMA-MAA block via acid hydrolysis.

x CH2

y CH2

C C

O

O CH2

H3C

CH3

CH3

CH3

C C

+

( O

CH2

MTS, TBABB

)x (

C

THF, 25oC DMA added first

O

C

O

CH2

CH2

CH2

N

N H3C

2-(dimethylamino)ethyl tetrahydropyranyl methacrylate (DMA) methacrylate (THPMA)

CH2

C C

)y O

( CH2 Acid hydrolysis

CH3

CH3

C

C

)y

C

O

) x ( CH2

C

0.1 M HCl/H2O

O

O

O

CH3

CH3

O

OH

O

O

CH2 CH2 N

CH3

DMA-THPMA block copolymer

H3C

CH3

DMA-MAA block copolymer

Figure 5.11 Synthesis and chemical structure of the precursor DMA-THPMA block copolymer and conversion to the zwitterionic DMA-MAA block copolymer

167


CH 3

CH 3

)n (

(

)m

O

C

O

C

O

O

Micellization 95:5 H2O/THF

O

+ +

CH 3

Shell cross-linking via quaternization using BIEE, at 25oC

+ + + + +

N H 3C

Partially cross-linked DMA corona

Solvated DMA corona

+

+

+ +

THP Acid hydrolysis HCl/H2O, 25oC, 24 h

+ + + + +

+

+

Add

THPMA core

THPMA core

THP CH3

)n (

(

C

O

)m C

O

OH

O

Shell cross-linking via esterification using BIEE, at 60oC

Micellization 60oC, pH 10

Partially cross-linked MAA corona

Partially cross-linked MAA corona (i) Cool to 25oC (ii) HCl KOH

+ + + + + + ++ +

N H3 C

CH3

DMA-MAA diblock copolymer Figure 5.12

Hydrophilic MAA core

BIEE = ICH2CH2-O-CH2CH2-O-CH2CH2I Solvated MAA corona

CH3

+ + + + + + + + +

Type I SCK micelle

DMA-THPMA diblock copolymer Acid hydrolysis HCl/H2O, 25oC, 24 h

Partially cross-linked DMA corona

DMA core

DMA core

Type II SCK micelle

Reaction scheme for the synthesis of Type I and Type II zwitterionic SCK micelles. Note that the same block copolymer precursor and cross-linking agent (BIEE) is used in each route.

168

ydrophilic DMA core


The resulting zwitterionic block copolymer forms micelles in aqueous media at pH 10 and 60oC, with the DMA block forming inverted micelle core and the MAA block forming the solvated corona.27 Prior to micelle cross-linking, several control experiments were carried out. Both DMA homopolymer and MAA homopolymers (converted from THPMA homopolymer via acid hydrolysis) were reacted in turn with BIEE. While cross-linking of the DMA homopolymer proceeds via quaternisation chemistry, esterification occurs in the cross-linking of the MAA homopolymer. Cross-linking of the MAA homopolymer was relatively fast and resulted in a white precipitate within 20-30 min at 25oC. In contrast, cross-linking of the DMA homopolymer required longer reaction times (2-4 days) at room temperature to achieve a high degree of cross-linking with BIEE. These observations suggested that we should be able to achieve selective shell cross-linking of the DMAMAA block copolymer, with little or no core cross-linking of the DMA residues. Table 5.2 A summary of the molecular weights, solution conditions and hydrodynamic diameters of the precursor block copolymers (both DMA-THPMA and DMAMAA) and their SCK micelles before and after deprotection BLOCK COPOLYMER

DMA-THPMA

DMA content a (mol%)

Mn of Maximum Hydrodynamic diameter (nm)d Degree of Solution precursorb pH Precursor Type I Type II (g mol-1) cross-linking (mol%) Micelle

51 51 64 64 82 82

34,000 25,350c 35,700 29,000c 24,700 22,350c

48

After deprotection

51 51

34,000 25,350c

MAA-DMAf MAA-DMAf MAA-DMAf

43 43 43

MAA-DMAg MAA-DMAg MAA-DMAg

51 51 51

After deprotection

DMA-THPMA After deprotection

DMA-THPMA After deprotection

DMA-THPMA

7-8 2/10 7-8 2/10 7-8 2/10

22 --20 --24 ---

29 32/33 28 30/31 38 31/32

-------

60 60

7-8 10

-----

35 62

-----

29,900 29,900 29,900

42 42 42

10 10 2

55 unimers unimers

-------

42 40 35

25,350 25,350 25,350

50 50 50

10 10 2

57e unimers unimers

-------

58e 49 47

50 50

a) As determined by 1H NMR spectroscopy b) As determined by GPC (calibrated with poly(methyl methacrylate) standards)

c) d) e) f) g)

Calculated assuming 100% deprotection As determined by PCS At 60 oC D2O/d8 THF mixture was used in the SCK synthesis In the presence of 1 M KCl

169

-----


5.3.5.1. Route I: After cross-linking of the DMA-THPMA Type I micelles, the resulting shell cross-linked micelle diameter was between 28-38 nm depending on comonomer compositions (see Table 5.2). These SCK micelles were dried in a vacuum oven at 60oC for 2 days. The dried micelles could not be redissolved in either water or in D2O for NMR studies. This is probably due to the hydrophobic nature of the THPMA blocks in the micelle core. Bearing this in mind, the shell cross-linking reaction was also carried out in D2O using d8 THF as the co-solvent in order to get an NMR spectrum of the DMATHPMA SCK micelles. Deprotection of the THPMA residues in the micelle cores was carried out via acid hydrolysis at pH 1. The resulting Type I zwitterionic SCK micelles were obtained with MAA cores and cationic DMA coronas. Precipitation from solution occurred at the IEP. After washing the precipitated micelles with water (pH 7), they were either dried in a vacuum oven at 60oC or redissolved by addition of acid or alkali. After this clean-up, the Type I SCK micelles were also washed with D2O and redissolved in DCl/D2O or NaOD/D2O for NMR studies. Small changes in micellar diameter were observed by PCS on varying the solution pH (see Table 5.3). The solubility, and also the degree of micelle swelling, depends on the solution pH. At low pH, the DMA block becomes protonated and more soluble while the MAA block becomes neutral and less solvated (see Figure 5.13). As expected, the neutral MAA residues lead to a reduction in the micellar diameter in both Type I and Type II SCK micelles. On the other hand, quaternised DMA shells may lead to larger SCK micelle. At higher pH, the MAA shell (Type I) or core (Type II) becomes more anionic, and therefore more hydrophilic. Thus the micelle size increases. However, the cross-linked DMA shell has the opposite effect because it is less hydrophilic at high pH due to deprotonation of the unquaternised DMA residues. As can be seen from Table 5.2, these effects tend to cancel each other and the overall micelle diameter did not change significantly on varying the solution pH.

5.3.5.2 NMR Studies of ‘Type I’ SCK Micelles:

After deprotection of the shell cross-linked DMA-THPMA micelles, the ‘Type I’ zwitterionic DMA-MAA SCK micelles were precipitated at their respective IEP’s, washed with H2O and dried in a vacuum oven at 60oC for 2 days. Some of the precipitate

170


was also washed with D2O and dissolved in D2O at both pH 2 (DCl) and pH 10 (NaOD) for NMR studies. The NMR spectra of the Type I block copolymer micelles, both before and after cross-linking of the DMA residues and after deprotection of the THP groups are shown in Figure 5.13. While the signals due to the DMA residues at δ 2.2 are visible, there are no signals attributable to the THPMA residues which form the hydrophobic micelle cores (see Figure 5.13a).

Dimethylamino protons of DMA residues N

THF

THF CH 3

H3C

Before cross-linking of DMA-THPMA block copolymer

A)

After crosslinking pH 7-8

B)

MAA backbone methyl groups After deprotection of theTHP groups

C)

After deprotection Type I and pH 2

D)

4.0

3.0

2.0

1.0

δ/ppm

Figure 5.13 Proton NMR spectra of: (a) a 51:49 DMA-THPMA precursor in (AB4) D2O (Mn = 34,000); (b) After shell cross-linking in D2O at room temperature (Type I); (c) After deprotection of the zwitterionic SCK micelle cores and adjusting the solution pH 10; (d) the same deprotected SCK micelles at pH 2. Note the marked ‘increase in intensity’ of the MAA signals in the micellar core as the THPMA block becomes deprotected via acid hydrolysis. The SCK synthesis was actually carried out in 5:95 d8THF/D2O to aid the NMR studies. After deprotection, d8THF and THP groups were removed by precipitation of the zwitterionic SCK micelles at IEPs (see spectrum c and spectrum d).

171


After shell cross-linking, the appearance of a new peak at δ 3.2 in Figure 5.13b is assigned to the quaternised DMA residues and indicates that cross-linking has occurred. After deprotection of the THP groups and removal of d8THF by precipitation of the zwitterionic SCK micelle at its IEP, it was redissolved in D2O by the addition of NaOD (see spectrum c) and DCl (see spectrum d). The increased peak integral at δ 0.7-1.1 is due to the backbone methacrylate protons of the now-solvated MAA block (see spectrum c). Comparing peak integrals, the comonomer ratio is similar to that of precursor block copolymer. This indicates that complete deprotection of the THPMA residues was achieved. In addition, the hydrophilicity of the micelle core varies with solution pH. The methacrylate backbone NMR signal of the neutral MAA block is much less intense at pH 2, as can be seen in Figure 5.13d. This suggests that the micelle core becomes at least partially dehydrated, which supports the decrease in SCK micelle diameter observed by PCS at low pH (see Table 5.2).

5.3.5.3 Cross-Linking of the MAA Corona (Route II): DMA-THPMA block copolymers were converted to the corresponding DMA-MAA zwitterionic block copolymers via acid hydrolysis (see Figure 5.11). In order to get DMA-MAA micelles (Type II), a 43:57 DMA-MAA block copolymer (0.25 g) was first dissolved as unimers in deionised water (100 ml) at pH 10. 1.0 M KCl was added in some cases, and the solution temperature was then raised to 60oC, which is higher than the cloud point of the DMA block. Under these conditions, the MAA block was fully ionised and formed anionic coronas, while the DMA block formed the micelle core. The micelle diameter measured by PCS was 55 nm. After adding the BIEE cross-linker (40 µl), the solution was kept stirring at 60oC for 2 hours. The resulting SCK micelle diameter was 42 nm at 60oC and pH 10. On cooling to 20oC, the micelle diameter remained almost unchanged at 40 nm. However, when the solution pH was lowered to pH 2 with HCl, the micellar diameter decreased to 35 nm. This deswelling was surprising: protonation of the DMA block on the micelle core was expected to lead to larger micelles. Presumably, micelle deswelling occurs due to the reduced solubility of the cross-linked MAA corona and, more importantly, noncross-linked MAA residues which migrate into the micelle core to complex with the cationic DMA residues. The reduced signal intensity of the methyl protons of the MAA backbone at δ 0.7-1.1 (see the spectrum b in Figure 5.14) at pH 2 support this electrostatic interaction. Slightly larger changes in micelle diameter were

172


observed in varying the comonomer ratio. Thus, the mean diameter of ‘Type II’ SCK micelles formed using a 51:49 DMA-MAA copolymer at pH 10 and at 60oC decreased from 57 nm to 49 nm as the solution was cooled to 20oC. However, there was a smaller decrease in micelle diameter on addition of HCl: at pH 2, the micelle diameter was 47 nm (see Table 5.2).

Dimethylamino protons of DMA residues N CH 3

H 3C

MAA backbone methyl protons

From esterification

A)

From esterification

4.0

Protonated Dimethylamino protons of DMA residues

3.0

2.0

B)

1.0

δ/ppm

Figure 5.14 Proton NMR spectra of Type II zwitterionic SCK micelles formed using the 43:57 DMA-MAA copolymer (AB5, Mn = 42,400) (a) at pH 10 and (b) at pH 2. The DMA block is in the micelle core. 5.3.5.4 FTIR Spectroscopy: FTIR studies of the dried Type I and Type II SCK micelles proved useful for assessing the conversion of the THPMA residues into MAA residues. Figure 5.15 shows the FTIR spectra of: a) a 51:49 DMA-THPMA block copolymer, b) the SCK micelles obtained from shell cross-linking of this 51:49 DMA-THPMA block copolymer, c) ‘Type I’ zwitterionic SCK micelles obtained after deprotection of the THPMA block and precipitation at its IEP and d) the same ‘Type I’ zwitterionic SCK micelles at pH 10 (i.e. above its IEP). There are no significant differences (i.e. no evidence for cross-linking) between the spectrum of the precursor copolymer (spectrum A) and that of the SCK micelles (spectrum B). Both spectrum C and spectrum D confirm

173


formation of the carboxylic acid groups, as expected. Prior to the hydrolysis of the DMATHPMA SCK micelles, the carbonyl region comprises a sharp peak at 1745 cm-1 with a distinct shoulder at 1722 cm-1. After hydrolysis, formation of the potassium carboxylate salt resulted in the disappearance of the strong carboxylic acid band at 1745 cm-1 and new two absorption bands appeared at 1555 and 1450 cm-1 (see spectrum D) which are characteristic of the carboxylate anion.29 These spectral changes indicate that deprotonation of the MAA blocks in the micelle cores can be easily achieved. Similar observations were reported for both MAA homopolymers and various MAA-based block copolymers by Rannard et al.,30 Vamvakaki et al31,32 and Lowe et al.27

0 .2 0

A)

0 .1 0

0 .0 0

B)

0 .2 0

0 .0 0

C)

0 .0 5

0 .0 0

D)

0 .0 5

0 .0 0 1800

1600

1400

W a v e n u m b e r s ( c m -1 ) Figure 5.15 FTIR spectra of the carbonyl region for: a) the linear 51:49 DMA-THPMA block copolymer; b) the same block copolymer after shell cross-linking (Type I micelles with THPMA cores); c) after deprotection of the THPMA residues; d) after addition of KOH to form potassium carboxylate residues. As can be seen in Figure 5.16, the ester carbonyl band intensity at 1745 cm-1 decreases relative to that of the carboxylate anion band at 1555 cm-1 as the MAA content of the block copolymer is reduced. This suggests that deprotection of the THPMA cores was successfully achieved.

174


0.30 0.25

A)

0.20 0.15

B)

0.10 0.05

C)

0.00 -0.05 1800

1600

1400

1200 -1

Wavenumbers (cm ) Figure 5.16 FTIR spectra of the carbonyl region for selected SCK micelles with differing DMA contents (potassium carboxylate formation in each case): a) a 43:57 copolymer (DMA core), b) a 51:49 copolymer (MAA core), c) a 64:36 copolymer (MAA core).

5.3.5.5 Zeta Potential Measurements: One fascinating aspect of these zwitterionic SCK micelles is that they exhibit IEP’s. Thus, at a certain pH (the IEP) the micelles become electrically neutral and are precipitated quantitatively from aqueous solution. In this sense they behave like ‘synthetic proteins’. Addition of acid or base leads to complete redissolution of the micelles. This precipitation-dissolution behaviour is well known for conventional proteins and their synthetic analogues. However, as far as we are aware, it has not been reported before for micelles, SCK micelles or nanoparticles. The precise IEP depends mainly on the relative block compositions.28 A secondary factor is the degree of shell cross-linking: quaternisation of DMA residues with BIEE leads to a permanent increase in the cationic charge density in the corona of the Type I micelles, whereas esterification of the MAA residues with BIEE leads to irreversible reduction in the anionic charge density of the Type II micelles. Aqueous electrophoresis measurements are a useful method for determining the IEP of an SCK micelle. Zeta potential vs. pH curves are shown in Figure 5.17. The 51:49 DMA-THPMA SCK micelles have only positive zeta potentials across the whole pH range (curve a). After acid hydrolysis, the

175


51:49, 64:36 and 43:57 DMA-THPMA Type I SCK micelles each exhibited both positive and negative zeta potentials depending on solution pH (curves c, b and e). However, the ‘Type I’ zwitterionic SCK micelles with only 18 mol % MAA content has only a positive zeta potentials over the whole pH range (curve d).

60

Zeta Potential (mV)

40

20 a) d) 0

-20

b)

e)

c)

-40

-60 2

4

6

8

10

12

pH

Figure 5.17 Zeta potential vs. pH curves obtained for: a) Type I SCK micelles prepared using a 51:49 DMA-THPMA block copolymer prior to acid hydrolysis (), b) Type I zwitterionic SCK micelles prepared using the same copolymer after acid hydrolysis (∇), c) Type I zwitterionic SCK micelles prepared using a 64:36 precursor after acid hydrolysis (Ο), d) Type I zwitterionic SCK micelles prepared using a 82:18 precursor after acid hydrolysis ( containing plus), e) Type II zwitterionic SCK micelles prepared using a 43:57 DMAMAA block copolymer (z).

Here, the number of quaternised, cross-linked DMA residues must be greater than the number of anionic MAA residues. This is reasonable since the BIEE/DMA molar ratio was 0.25 Thus no IEP can be observed in this case. All the other SCK micelles have large positive zeta potentials at low pH and exhibit isoelectric points which depend on both the block compositions and the degree (and nature) of the shell cross-linking (see Table 5.3). Table 5.3 Summary of the isoelectric points of the DMA-MAA precursor block copolymers and the corresponding Type I and Type II SCK micelles 176


SAMPLES

DMA Mn content (precursor) TYPE IEP IEP (Calc) (Titration) (mol%)a (g mol-1)b

Degree of IEPc cross-linking (theory)

PRECURSORS

DMA-MAA DMA-MAA DMA-MAA DMA-MAA

5.62d 6.74d 7.40d 8.56d

---------

---------

II

5.60

5.50

42

I I I

7.02 7.60 ---

7.60 8.30 ---

48 50 50

43 51 64 82

29,900 25,350 29,000 22,350

---------

DMA-MAA

43

29,900

DMA-MAA DMA-MAA DMA-MAA

51 64 82

25,350 29,000 22,350

6.83d 6.86d 7.89d 8.65d

SCKs

a) As determined by 1H NMR spectroscopy

b) Calculated assuming 100% deprotection c) As determined from zeta potential vs. pH data on 0.02% solutions. d) A. B. Lowe, PhD thesis, University of Sussex, 1997.

The isoelectric points of the zwitterionic SCK micelles increase with increasing DMA content in the copolymer (see Table 5.3). For example, the IEP of the 64:36 DMA-MAA ‘Type I’ zwitterionic SCK micelle is at pH 7.6, which is higher than the IEP of 7.02 for the 51:49 DMA-MAA SCK micelles (see Table 5.3). Similar increases in the IEP of the precursor zwitterionic block copolymers was reported by Lowe et al.27-28 The observation of these IEP’s confirmed that formation of the MAA block via acid hydrolysis was successfully achieved at room temperature. Above pH 8, the particles have more negative charge than positive charge, since the DMA residues are extensively deprotonated at this pH(ref lee and gast) and the MAA residues are increasingly ionised. At low pH, the particles have an overall positive surface charges due to the protonated DMA and the protonated (neutral) MAA residues. However, SCK micelle IEP’s determined from zeta potential vs. pH are higher than the IEP’s of the precursor block copolymers.28 This is presumably due to the structure of the SCK micelles. The IEP’s of the zwitterionic SCK micelles were also determined by acid titration, as judged by the onset of precipitation. These values are lower than those IEP’s obtained from zetapotential measurements but agree with the IEP’s of the linear precursors (see Table 5.3). In the case of the Type II zwitterionic SCK micelles, the cationic charge is located in the micelle interior and the anionic charge is reduced by partial shell cross-linking of the MAA corona. Hence, after cross-linking, the effective DMA/MAA molar ratio will be 177


higher. As a result, an increase in the IEP would be expected. Type II SCK micelles synthesised using a 43:57 DMA-MAA block copolymer have an IEP at pH 5.50 (curve e). This is significantly lower than the IEP of 6.83 calculated for the corresponding linear block copolymer. However, the IEP measured by acid titration is 5.6 which is in good agreement with the zeta potential IEP. The DMA residues in the micelle cores are only partially solvated, as judged by NMR (see Figure 5.14). On comparing the relevant peak integrals, the appearent DMA content of these SCK micelles was only 30 mol%, compared to the expected 43 mol%. This could be due to the relatively high degree of shell cross-linking, which limits the core visibility by NMR spectroscopy.21

The micelle diameter of the Type II SCK micelles prepared using the 51:49 DMA-MAA block copolymer decreased from 58 to 49 nm as the temperature of the alkaline solution micelle was lowered to 20oC. This was a surprising result because hydration of the micelle core should lead to micelle swelling. Presumably, after hydration of the DMA core by lowering the solution temperature to room temperature, the cationic DMA residues interract with the partially cross-linked anionic MAA corona, leading to smaller, more compact micelles. As can be seen from Table 5.2, the observed deswelling is probably due to the interaction between the protonated DMA micelle core and the partially cross-linked MAA corona as the solution pH was lowered from pH 10 to pH 2.

5.3.5.6 TEM Studies: Representative electron micrographs of both Type I and Type II zwitterionic SCK micelles are shown in Figure 5.18. This confirms the relatively uniform particle size and spherical morphology of the SCK micelles and suggest a numberaverage ‘Type I’ micelle diameter of approximately 15-30 nm (see Figure 5.18A). As can be seen in Figure 5.18B, the Type II SCK micelle diameter is somewhat larger (around 20-40 nm). Allowing for dehydration and polydispersity effects, these values are in reasonable agreement with the intensity-average diameter of both 33 nm (Type I) and 40 nm diameter (Type II) obtained from PCS.

178


A

B

Figure 5.18 Transmission electron micrographs of zwitterionic SCK micelles: a) Type I micelles prepared with a 51:49 DMA-THPMA block copolymer (average micelle diameter is 22 nm); b) Type II SCK micelles prepared using a 43:57 DMA-MAA block copolymer (average micelle diameter is 30 nm). 5.4 CONCLUSIONS

179


In summary, several novel SCK micelles based on tertiary amine methacrylate block copolymers have been synthesized using a bifunctional cross-linker in aqueous media. Unlike the SCK micelles described by Wooley’s group, the cores of the DMA-MEMAbased SCK micelles can be reversibly hydrated or dehydrated, depending on the solution temperature or salt concentration. SCK micelles with more hydrophobic cores were prepared using DMA-DEA and DMA-DPA diblock copolymers. Partial quaternisation of the DMA residues prior to shell cross-linking increases the solubility of the SCK micelles. Partial protonation of the DEA cores of the SCK micelles was observed by NMR studies. Two types of novel zwitterionic SCK micelles were also prepared from DMA-based diblock copolymers using the same 1,2-bis-(2-iodoethoxy)ethane crosslinker in aqueous solution. Type I micelles, which have anionic cores and cationic coronas, and Type II micelles, which have cationic cores and anionic coronas were obtained, depending on the reaction sequence. Both types of micelles exhibited isoelectric points in aqueous solution. Clearly this unusual aqueous solution behaviour offers considerable scope for the isolation, purification and harvesting of these zwitterionic SCK micelles in various applications. Since these novel nanoparticles contain both acidic (MAA) and basic (DMA) binding sites, they are expected to be suitable delivery vehicles for a wide range of ionic ‘activities’ (e.g. drugs or pesticides).

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180


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