pH-Responsive Antibacterial Surfaces Based on Cross-Linked Phosphonium Polymers

With growing concerns regarding biofilms and the development of antibiotic resistance, there is significant interest in antibacterial surfaces. Surfaces that can exhibit antibacterial activity in response to stimuli associated with bacteria and biofilm development are particularly attractive as they can mitigate off-target toxicity and minimize antimicrobial resistance. One such stimulus is a local reduction in pH, which is associated with the production of organic acids by bacteria. We describe here coatings composed of phosphonium monomers and pH-sensitive acetal or ketal-containing cross-linkers that are designed to break down and release active phosphonium species at mildly acidic pH. Four styrenic phosphonium monomers were investigated, and the tributyl(4-vinylbenzyl)phosphonium chloride and triphenyl(4-vinylbenzyl)phosphonium chloride monomers provided coatings with efficient curing, water contact angles of 50–62°, and surface charge densities of >1016 cations cm–2. Coatings prepared from these monomers using the acetal cross-linker were very stable at pH 4.5–7.4 over 3 weeks, whereas those containing the ketal cross-linker exhibited pH-dependent degradation, with complete degradation over 1 week at pH 5. At pH 5, the ketal cross-linker coatings were confirmed to release phosphonium species that effectively killed Escherichia coli and Staphylococcous aureus, whereas the same coatings at pH 7.4 as well as the acetal cross-linker coatings at both pH 5 and 7.4 released minimally active concentrations of species. The effects of the coatings on bacteria seeded directly on the surfaces were also examined, and it was found that while some coatings exhibited modest antibacterial activity at pH 7.4 or with the slowly degrading acetal cross-linker, coatings containing the rapidly degradable ketal cross-linker consistently provided the highest inhibition of bacterial growth at pH 5. These results were confirmed by live/dead staining. Overall, this work indicates the potential of pH-sensitive phosphonium surfaces to provide pH-dependent bacterial killing, which can potentially prevent biofilm development.