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

Abstract

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 Staphylococcus aureus (MRSA) and Gram-negative (Escherichia coli) 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.