Tunable pH- and Temperature-Sensitive Copolymer Libraries by Reversible Addition−Fragmentation Chain Transfer Copolymerizations of Methacrylates

Abstract

Reversible addition-fragmentation chain transfer (RAFT) polymerizations have been performed on a Chemspeed Accelerator SLT100 automated synthesizer to polymerize N,N-(dimethylamino)ethyl methacrylate (DMAEMA) and poly(ethylene glycol) methyl ether methacrylate (PEGMA) at 70 °C. Azobis(isobutyronitrile) (AIBN) was used as source of radicals and 2-cyano-2-butyl dithiobenzoate (CBDB) as RAFT agent. A complete screening in composition of P(DMAEMA-stat-PEGMA) copolymers was elaborated from 0% of PEGMA to 100% of PEGMA. All polydispersity indices of the obtained copolymers are comprised between 1.11 and 1.30. The reactivity ratios have been determined by the extended Kelen-Tu ¨do ¨s method (r DMAEMA ) 0.93 and r PEGMA ) 0.66). The behavior of the pH-and temperature-sensitive copolymers was studied in aqueous solution by measuring the lower critical solution temperature (LCST) by UV/vis spectroscopy. The measurements were performed at three different pH values (4, 7, and 10). At pH 7 and pH 10 it has been observed that the LCST is increasing linearly with the wt % PEGMA in the copolymer feed. On the contrary, at pH 4, the hydrophilicity of the P(DMAEMA-stat-PEGMA) copolymers is too high due to the protonation of the DMAEMA units. Thus, no LCST has been detected for most of them. By varying the pH and the composition of the P(DMAEMA-stat-PEGMA) copolymers, the LCST can be easily tuned between 34.7 and 82.0 °C.

Living Radical Polymerization by the RAFT Process - A Second Update

“…Symmetrical trithiocarbonates are frequently synthesized from the corresponding halide, and carbon disulfide in the presence of a base. Aoyagi and Endo [290] have shown that this process can be performed on benzyl halides, and stoichiometric carbon disulfide at low temperature (40 • C) in air with potassium bicarbonate as base to provide near quantitative yields of the corresponding dibenzyl trithiocarbonates (111)(112)(113)(114).…”

“…[114,115,251] High throughput methods have been applied to synthesize libraries of methacrylate polymers (MAA, various oligo(ethylene glycol) methacrylates and copolymers of MAA with PEGMA, [108] MMA, DMAEMA and block and statistical copolymers, [114] and copolymers of DMAEMA with PEGMA [113] ) for evaluating the composition dependence of the lower critical solution temperature (LCST).…”

Synthesis of Stimuli-responsive, Water-soluble Poly[2-(dimethylamino)ethyl methacrylate/styrene] Statistical Copolymers by Nitroxide Mediated Polymerization

“…The LCST of such a polymer can be affected by many parameters, including molecular weight [50,51], polymer composition [9,52,53], solution concentration [50], and pH [8,9] in the case of PDMAEMA. Because the DMAEMA/styrene copolymerizations using NHS-BlocBuilder were relatively controlled as demonstrated earlier, final copolymers obtained have similar M n (10.4 ± 0.9 kg mol −1 ) and PDI (1.42 ± 0.12).…”

“…It exhibits a lower critical solution temperature (LCST)-type phase separation upon heating at neutral or basic conditions and is completely water-soluble in acidic media [8][9][10]. To fine-tune the transition conditions and polymer properties, DMAEMA has been incorporated into block copolymers with various counter blocks such as the pH-sensitive poly(2-vinyl pyrindine) to obtain pH-dependent micelles [8], a temperature-responsive block such as POEGMA [9] and PNIPAM [11] to alter the LCST, and a hydrophobic block such as poly(2-(N-carbazolyl)ethyl methacrylate) to make amphiphilic diblock copolymers with hole-transport properties [12].…”

“…To achieve these goals with relatively robust experimental conditions, controlled radical polymerization (CRP) techniques like atom transfer radical polymerization (ATRP), reversible addition-fragmentation transfer (RAFT) and nitroxide mediated polymerization (NMP) have emerged [13]. For DMAEMA specifically, ATRP [14][15][16] and RAFT [9,17,18] have been successfully applied to obtain well-defined (co)polymers. NMP, being a solely thermal process, does not involve metal catalysts that ATRP requires or bimolecular exchange with sulfur-based agents as in RAFT, which is potentially advantageous for synthesis of non-cytotoxic polymers for biomedical applications [19][20][21] or electronic applications where metal contamination is undesirable [21].…”