Radical‐medicated end‐group transformation of amphiphilic methacrylate random copolymers for modulation of antimicrobial and hemolytic activities

Abstract

ABSTRACTThis work describes synthesis of antimicrobial methacrylate copolymers by reversible addition‐fragmentation chain transfer (RAFT) polymerization and examines the versatility of this approach for improving chemical optimization to create potent, non‐toxic antimicrobial polymers. Specifically, this study focuses on the radical‐mediated transformation of end group of antimicrobial peptide‐mimetic polymer. RAFT polymerization using 2‐cyano‐2‐yl‐dithiobenzoate provided a statistical methacrylate copolymer consisting of aminobutyl and ethyl groups in the side chains. The following radical‐mediated modification using free radical initiators successfully transformed the ω‐end group of parent copolymer from dithiobenzoate to a cyanoisobutyl or aminoethyl cyanopentanoate group without any significant changes to the polymer molecular weight. In general, the parent polymer and variants showed a broad spectrum of activity against a panel of bacteria, but low hemolytic activity against human red blood cells. The parent copolymer with the dithiobenzoate end‐group showed highest antimicrobial and hemolytic activities as compared with other copolymers. The copolymers caused membrane depolarization in Staphylococcus aureus, while the ability of copolymers for membrane disruption is not dependent on the end‐group structures. The synthetic route reported in this study will be useful for further study of the role of polymer end‐groups in the antimicrobial activity of copolymers. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 304–312