Rapid evolution of antibiotic resistant bacteria requires consistent development of antimicrobial agents for which resistance mechanisms are not known. Polymeric structures decorated with transition metal complexes pose a promising strategy for this purpose by offering unique mechanisms of action and the potential to evade common resistance strategies. A series of structure-activity relationship studies using polyacrylate microgels with embedded copper(II) complexes in broth microdilution assays with Staphylococcus aureus demonstrated that antimicrobial activity of the material is related to modular design in terms of co-monomer polarity, Cu(II) ion binding strength of polymerizable ligands, and counterion coordination to metal complexes during synthesis. A microgel Cu2LP(EG) (L = VBbsdpo) emerged with optimized minimum inhibitory concentration of 0.39 ± 0.03 μg/mL resulting from synthesis using 60 mol% of crosslinking ethyleneglycol dimethacrylate, 40 mol% butyl acrylate, 0.5 mol% VBbsdpo ligand in the presence of 1 mol% Cu(II) ions and 5 mol% ethylene glycol counterions. Insight into antimicrobial properties reveal stable activity for a shelf life of greater than 18 months. Bactericidal activity toward S. aureus was observed at a concentration of 1.5x the MIC in less than 15 minutes. Additionally, 260 nm release assays indicate mechanism of action involves damage to bacterial membrane beyond repair. Despite having potent antimicrobial activity, there was no cytotoxic effect observed from microgels at their minimum inhibitory concentrations toward human dermal fibroblasts for 20 h exposure.

Modularly designed polyacrylate microgels for antibacterial activity against Staphylococcus aureus

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.