Oxygen‐Tolerant Photoredox Catalysis Triggers Nitric Oxide Release for Antibacterial Applications

Photoredox catalysis has emerged as a robust tool for chemical synthesis. However, it remains challenging to implement photoredox catalysis under physiological conditions due to the complex microenvironment and the quenching of photocatalyst by biologically relevant molecules such as oxygen. Here, we report that UV‐absorbing N,N′‐dinitroso‐1,4‐phenylenediamine derivatives can be selectively activated by fac‐Ir(ppy)3 photocatalyst within micellar nanoparticles under visible light irradiation (e.g., 500 nm) through photoredox catalysis in aerated aqueous solutions to form quinonediimine (QDI) residues with concomitant release of NO. Notably, the formation of QDI derivatives can actively scavenge the reactive oxygen species generated by fac‐Ir(ppy)3, thus avoiding oxygen quenching of the photocatalyst. Further, we exemplify that the oxygen‐tolerant photoredox catalysis‐mediated NO release can not only kill planktonic bacteria in vitro but also efficiently treat MRSA infections in vivo. Oxygen‐tolerant photoredox catalysis is used for the controlled release of nitric oxide signaling molecules under physiological conditions. This new NO‐releasing platform shows excellent antimicrobial activity and kills bacteria by hyperpolarizing and permeabilizing bacterial membranes, which can not only eradicate pathogens but also accelerate the healing of MRSA‐infected wounds.