Modularly designed polyacrylate microgels for antibacterial activity against Staphylococcus aureus.

by Clem, Carlie; Sharma, Babloo; Striegler, Susanne

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 Cu2L P (EG) (L = VBbsdpo) emerged with optimized min. inhibitory concn. of 0.39 ± 0.03 µg/mL resulting from synthesis using 60 mol% of crosslinking ethyleneglycol dimethacrylate, 40 mol% Bu 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 mo. Bactericidal activity toward S. aureus was obsd. at a concn. of 1.5x the MIC in less than 15 min. Addnl., 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 obsd. from microgels at their min. inhibitory concns. toward human dermal fibroblasts for 20 h exposure.