Effect of Chain Lengths on the Antibiofilm and Hemolytic Activities of Main-Chain Alternating Polysulfoniums

Unlike antibiotics with accurate chemical structures, polydisperse chain lengths of synthetic polycations usually result in undesirable variations of antibacterial performance, which obstructs their wide applications in many areas. Herein, we propose that main-chain sulfonium-based polymers with alternating sequences may be used as a potential solution to tackle this issue. Through the thiol–epoxy "click" step-growth polymerization and methylation, alternating polysulfoniums can be facilely prepared with polydispersity around 1.5 and a molecular weight ranging from 6000 to 50 000 g/mol. Within this tested range, constant minimum bactericidal concentration (MBC) values against a broad spectrum of clinically relevant bacteria and stable hemocompatibility are observed for polysulfoniums with different chemical compositions. Moreover, the representative polysulfonium can steadily inhibit the biofilm formation (∼75–90%) at 1.25–5 μg/mL and achieve 97–99.9% reduction of bacteria at 10–40 μg/mL in the 3 day mature biofilms. We hypothesize that the amphiphilicity of main-chain polysulfoniums displays less susceptibility to the dispersed polymer chains, probably because of their accurate alternating sequence and the location of all functional groups in the polymer main chain. The unique structural nature of the main-chain sulfonium-based alternating polymers can make them serve as a reliable platform for antibacterial applications in the field of synthetic polycations.