Synthesis of amphiphilic cationic polyesters and their antibacterial activity

Abstract

The search for new synthetic cationic biodegradable polymers with activities akin to those of host defense peptides continues to be a significant topic of scientific interest. We report the synthesis of a new class of water-dispersible fluorescent, amphiphilic cationic polyesters with positively charged naphthalene monoimide (NMI) pendants (P1, P2a/P2b, and P5) and assess the role of different structural parameters in dictating their broad-spectrum antibacterial properties against representative Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria. The cationic ammonium head group residing on the pendant NMI dyes allowed the dispersibility of these polyesters in water, while the hydrophobicity imparted by the aromatic dye and its propensity for π–π stacking resulted in the formation of well-defined, green-emitting, spherical nanoparticles with sufficient colloidal stability in water. Systematic structure–property relationship studies reveal that the polyester P2a, having a hydrophobic decyl chain attached to the pendant NMI, exhibits the most pronounced antibacterial activity, with a minimum inhibitory concentration (MIC) of 62.5 μg mL⁻¹ against both E. coli and S. aureus. Control cationic polyesters P1 (having a shorter methyl group in place of a longer decyl side chain), P2b (having a shorter backbone than P2a), P3 (without the pendant NMI dyes), and P5 (having randomly distributed NMI dyes and alkylated ammonium head groups along the polymer chain, unlike in same-centered P2a) exhibit much reduced or negligible biocidal effects, establishing the structural essentiality of the P2a polymer. The intrinsic fluorescent property of P2a enabled the study of its interaction with the bacterial cells and its role in membrane disruption. The enzymatically degradable biocidal polyesters were found to be sufficiently non-toxic to HeLa cells and exhibited no profound hemolytic activity at the obtained MIC values. The promising outcomes of this work and the labile polymer synthesis approach provide future opportunities for additional structural tailoring of polyester backbones to further improve their antibacterial properties.