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

Abstract

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.

Imidazolium‐Based Main‐Chain Copolymers With Alternating Sequences for Broad‐Spectrum Bactericidal Activity and Eradication of Bacterial Biofilms

“…It is reported that a molecular weight ranging from 6000 to 50 000 g mol −1 has no obvious trend of antibacterial activity and biocompatibility linked to the changing of polymer chain length. [ 52 ] In this exploration, 15 PIm + s with $$\overline {{M_n}} $$ ranging from 0.6 to 2.1 kDa were prepared. The detailed chemical structure information of them is displayed in Table 1 .…”

Enhanced Synergistic Antibacterial and Antibiofilm Efficacy of Main-Chain Polysulfoniums with Antibiotics by Balancing Charge Density and Amphiphilicity

“…The culture of bacteria strains and the planktonic MIC and MBC assays were carried out according to the procedure described in our previous report. 17 For the antibacterial kinetic study, the suspensions of bacteria (2 × 10 6 CFU/ mL) in TSB were prepared, followed by the addition of the PolyS + polymer (MIC of PolyS + ), Rif (MIC of Rif), and PolyS + /Rif combination (MIC of PolyS + and MIC of Rif) solution. At different incubation times, the mixture was sampled, diluted 100 times, and then transferred onto TSB agar plates and spread evenly.…”

“…However, the majority of work in this area so far is usually based on the alkylation reaction with a complete conversion to maintain the alternating sequence definition from the precursor polymers. 12,17,19 Quantitatively manipulating the alkylation level of main-chain sulfonium-containing polymers as a means to balance the charge density/amphiphilicity and thus regulate their biological activity has not been demonstrated. Due to the unique membrane interruption ability, cationic polymers can be used as not only direct antibacterial agents but also antibiotic adjuvants to increase the potency of antibiotics in treating Gram-negative bacterial infections.…”

“…Hence, the alkylation degree of thioether moieties affects not only the charge density but also the amphiphilicity of the polysulfoniums. However, the majority of work in this area so far is usually based on the alkylation reaction with a complete conversion to maintain the alternating sequence definition from the precursor polymers. ,, Quantitatively manipulating the alkylation level of main-chain sulfonium-containing polymers as a means to balance the charge density/amphiphilicity and thus regulate their biological activity has not been demonstrated.…”

“…16 A frequently used method to prepare main-chain sulfonium-or quaternary ammonium-containing polymers involves two steps. First, an alternating precursor polymer is synthesized by ring-opening polymerization, 16,17 polycondensation, 18 or click chemistry. 12 The sulfur or nitrogen atoms in the polymer backbone are then alkylated to access sulfonium or quaternary ammonium cations.…”