Synthesis of methacrylate- acrylamide based copolymer via reverse addition-fragmentation chain transfer polymerization with thiol- conjugation and thermoresponsive studies

Abstract

The potential of poly(2-hydroxyethyl methacrylate)-random-poly(2-chloroethyl methacrylate)-block-poly(N-isopropylacryl-amide) (PHEMA-r-PCEMA-b-PNIPAM) for biological purpose was investigated. In this study, the synthetic strategies to prepare this copolymer were developed. Initially, PHEMA and PNIPAM were synthesized via reversible addition-fragmentation chain transfer (RAFT) radical polymerization to obtain a controlled molecular weight of the polymer. 4-Cyanopentanoic acid dithiobenzoate (CPADB) and 4,4’-azobis(4-cyanopentanoic acid) (ACPA) were chosen as the RAFT agent and initiator due to its compatibility with both monomers. In order to replace hydroxyl group (-OH) in PHEMA macroRAFT with chlorine (-Cl), thionyl chloride (SOCl2) was used as chlorinating agent and copolymer of PHEMA-r-PCEMA was successfully synthesized. The targeted copolymer, PHEMA-r-PCEMA-b-PNIPAM, was successfully synthesized by polymerizing PHEMA-r-PCEMA with N-isopropylacrylamide (NIPAM) monomer. The change of lower critical solution temperature (LCST) points for PNIPAM macroRAFT, PHEMA-b-PNIPAM and PHEMA-r-PCEMA-b-PNIPAM were observed. A decreasing trend of temperature was spotted as the copolymer hydrophobicity in aqueous solution was increased. Both PHEMA-r-PCEMA and PHEMA-r-PCEMA-b-PNIPAM were reacted with thiolglycerol to form a thioester via thiol-halogen SN2 nucleophilic substitution. PHEMA-r-PCEMA-b-PNIPAM potential as protein- polymer modification material was investigated by reacting PHEMA-r-PCEMA-b-PNIPAM with cysteine. Based on the 1H NMR result, chlorine (-Cl) was successfully substituted with cysteine. Thus, PHEMA-r-PCEMA-b-PNIPAM can potentially be used for biological applications.