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 systematically π-extended benzohydrazide aggregation-induced emission luminogens (AIEgens) that act as efficient metal-free photo-responsive antimicrobial catalysts. 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 absorption into the visible region and enhancing ROS 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 enzymes such as laccase. Critically, G0Ant demonstrated potent light-activated antibacterial efficacy against both Gram-positive antibiotic resistant Staphylococcus aureus (MRSA) and Gram-negative (E. coli) strains, causing severe membrane disruption while showing minimal dark toxicity and good biocompatibility toward mammalian cells. These findings establish π-extension of benzohydrazide-based AIEgens as a rational design principle to engineer visible-light responsive suprazymes for safe, sustainable, and effective antimicrobial therapy.