Visible-light-responsive supramolecular enzyme mimics for combating antimicrobial resistance

The global rise of antimicrobial resistance has created an urgent need for alternative strategies that can overcome the limitations of conventional drug-resistance mechanisms. Light-assisted antimicrobial therapy, particularly photodynamic inactivation, offers spatial and temporal control while minimizing the likelihood of resistance. Since biomedical applications demand visible-light-responsive catalysts that enable deeper tissue penetration and minimize photodamage, designing systems that avoid reliance on UV excitation is essential. This work reports a supramolecular oxidase mimic "suprazyme" based on benzohydrazide aggregation-induced emission luminogens (AIEgens) with systematic π-extension that act as efficient metal-free photo-responsive antimicrobial agents. By extending the aromatic core from benzene (G₀Ben) to naphthalene (G₀Nap) and anthracene (G₀Ant), we progressively narrowed the band gap (3.1 eV to 2.0 eV), red-shifting the absorption into the visible region and enhancing the reactive oxygen species generation under white light. Among the series, G₀Ant exhibited the most robust oxidase-like activity, efficiently producing superoxide radicals without requiring exogenous H₂O₂. The assemblies displayed excellent stability against variations in ionic strength, pH, and temperature, outperforming natural oxidase enzymes such as laccase. Critically, G₀Ant demonstrated potent light-activated antibacterial efficacy against both Gram-positive methicillin resistant <i>Staphylococcus aureus</i> (MRSA) and Gram-negative (<i>Escherichia coli</i>) strains, causing severe membrane disruption while showing minimal dark toxicity and good biocompatibility toward mammalian cells. These findings establish the π-extension of benzohydrazide-based AIEgens as a rational design principle to engineer visible-light-responsive suprazymes for safe, sustainable, and effective antimicrobial therapy.