Synthesis, characterization and cell selectivity of poly(quaternary ammonium chlorides): effect of the degree of quaternization and copolymer composition

Abstract

Antimicrobial resistance is a global problem due to widespread evolution of resistant pathogens in both health care and community. Polymeric quaternary ammonium and imidazolium chlorides are well known for their antibacterial activity and have the potential to address this problem. In spite of the widespread reports on quaternary ammonium polymers, there is no facile, common synthetic route available for the preparation of these cationic polymers by which the cationic species can be varied in a facile manner. Particularly, such a common synthetic route should enable changing the cationic source conveniently, altering the charge density of the polymer, and tuning the structure of the cationic polymer to influence various characteristics like the hydrophilic–hydrophobic balance, H-bonding, π–π interactions and donor–acceptor interactions. Importantly, the influence of systematically changing the charge density of the cationic polymer on antibacterial activity as well as its effect on toxicity is not well studied. Moreover, since the properties of polymers can be enhanced through copolymerization, the roles of the other constituents of the cationic polymer introduced through copolymerization on the aforementioned characteristics of the cationic polymer are worth investigating. In this work, we report the synthesis of a series of homo- and copolymers containing various quaternary ammonium groups. We also investigated their selectivity in discriminating microbial and mammalian cells. Combining the antimicrobial and hemolytic activities of the polymers allowed us to obtain structure–activity relationships and identify polymers with good selectivity for further refinement.