Electron competition in azobenzene programs infection-adaptive antibacterial therapy

Conventional stimulus-responsive antibacterial systems generally operate through binary trigger-activation mechanisms, making them poorly suited to evolving infection microenvironments and thereby contributing to persistent infection and resistance development. Here, we establish an azobenzene-based kinetic regulatory system in which oxygen gradients commonly present in infected tissues continuously program reaction kinetics through electron competition. Oxygen acts as a competing electron acceptor within the reductive reaction network, partitioning electron transfer between azo reduction and oxygen consumption. Substituent electronic structures further reshape reduction propensity, encoding distinct kinetic behaviors. These electronically programmed kinetics translated into adaptive nanoscale dissociation and drug-release profiles: Electron-rich azobenzenes rapidly disassembled under severe hypoxia, whereas electron-withdrawing structures sustained release under mild hypoxia, generating infection state-adaptive antibacterial outputs. Moreover, the same electronic features governing reduction kinetics also reduced the reactivity and toxicity of reductive metabolites. This work establishes electron competition as a strategy for converting environmental gradients into continuous kinetic outputs for adaptive antibacterial therapy.