Block versus Random Amphiphilic Copolymers as Antibacterial Agents

TLDR

Different single‑chain conformations of block versus random amphiphilic copolymers are thought to influence antibacterial action and mechanisms. The study synthesized amphiphilic block and random poly(vinyl ether) copolymers via base‑assisted living cationic polymerization to assess antibacterial and hemolytic activities. Block copolymers show comparable antibacterial potency to random copolymers but are markedly less hemolytic, selectively permeabilize bacterial lipid membranes, and act at sub‑CAC concentrations, indicating that polymer aggregation is not required for antibacterial activity.

Abstract

We examined the antibacterial and hemolytic activities in a series of amphiphilic block and random copolymers of poly(vinyl ether) derivatives prepared by base-assisting living cationic polymerization. Block and random amphiphilic copolymers with similar monomer compositions showed the same level of activity against Escherichia coli. However, the block copolymers are much less hemolytic compared to the highly hemolytic random copolymers. These results indicate that the amphiphilic copolymer structure is a key determinant of activity. Furthermore, the block copolymers induced dye leakage from lipid vesicles consisting of E. coli-type lipids, but not mammalian lipids, while the random copolymers disrupted both types of vesicles. In addition, both copolymers displayed bactericidal and hemolytic activities at concentrations 1 or 2 orders of magnitude lower than their critical (intermolecular) aggregation concentrations (CACs), as determined by light scattering measurements. This suggests that polymer aggregation or macromolecular assembly is not a requisite for the antibacterial activity and selectivity against bacteria over human red blood cells (RBCs). We speculate that different single-chain conformations between the block and random copolymers play an important role in the antibacterial action and underlying antibacterial mechanisms.