Photocatalytic antibacterial mechanism of a highly cationic ruthenium-phenylboronic acid complex for selective recognition of gram-positive bacteria.

Methicillin-resistant Staphylococcus aureus (MRSA) is a prevalent multidrug-resistant pathogen that poses a serious threat to human health. Herein, two phenylboronic acid (PBA)-functionalized ruthenium polypyridyl complexes, Ru2 and Ru3, were rationally developed from the parent complex Ru1. Among them, Ru3, incorporating PBA and quaternary ammonium groups, exhibited potent and selective antibacterial activity against MRSA through enhanced PBA-peptidoglycan recognition and electrostatic interactions. Upon 465 nm irradiation, Ru3 generated 1O2 and O2•- while promoting photocatalytic NADH oxidation, thereby disrupting bacterial redox and energy homeostasis. NADH oxidation occurred prior to ATP depletion and membrane damage, supporting its contribution as an early metabolic event, while ROS-mediated oxidative damage provided a complementary antibacterial mechanism. Furthermore, Ru3 showed favorable biocompatibility and significantly accelerated wound healing in MRSA-infected mice under light irradiation. Overall, this study highlights a rational strategy for developing ruthenium-based antibacterial agents that integrate bacterial recognition with complementary photochemical and metabolic mechanisms.