Asymmetrically Substituted Poly(diitaconates) Obtained by Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization: Synthesis, Copolymerization Parameters, and Antimicrobial Activity

Abstract

Asymmetrically substituted poly(diitaconate) copolymers are synthesized from 1-((N-tert-butoxycarbonyl)-2-aminoethyl)-4-propyl diitaconate (PrIA) and different comonomers (N,N-dimethyl-acrylamide, DMAA; acrylic acid; or ((N-tert-butoxycarbonyl)-2-aminoethyl)methacrylate) by reversible addition–fragmentation chain transfer polymerization (RAFT). The RAFT copolymerization parameters of PrIA and DMAA are rDMAA = 0.49 and rPrIA = 0.17, compared to rDMAA = 0.52 and rPrIA = 0.54 obtained by free radical copolymerization (FRP). Thus, the RAFT process has a stronger trend to alternating polymerization than the FRP process. The polydispersity index of the RAFT copolymers is around 1.2–1.8, compared to 2.8–2.9 for the corresponding FRP copolymers. After removal of the tert-butoxycarbonyl protective groups, antimicrobially active synthetic mimics of antimicrobial peptides are obtained. The thus activated poly(PrIA-co-DMAA) copolymers (repeat unit ratio 1:1) have an increasing activity against Escherichia coli and Staphylococcus aureus with increasing molar mass. The RAFT copolymers are slightly more active and less toxic than comparable FRP polymers, leading to a higher selectivity for bacteria over mammalian cells. Higher molar fractions of PrIA in poly(PrIA-co-DMAA) copolymers (up to 80 mol%) do not increase their antimicrobial activity; reduction of the BuIA content in poly(BuIA-DMAA) (down to 10 mol%) leads to a loss of activity against both E. coli and S. aureus.