Atomic Ga Site Enables Photonanozymes with Specific Inhibition Modes for Primary Drug Screening.

Enzyme inhibition plays a crucial role in drug discovery by governing interactions between molecules and distinct enzymatic sites, facilitating the identification of early drug candidates. However, most nanozymes have been limited to single active site inhibition models, leaving gaps in understanding inhibitor interactions and their dynamic modulation by external stimuli. Hence, an in-depth understanding of nanozyme inhibition across different functional domains, particularly under external stimuli like light irradiation, remains challenging. Herein, we report a carbon nitride photonanozyme with atomically dispersed Ga-N3-coupled cyano sites (Ga-CN) for analyzing and screening antithyroid drugs via photoregulated inhibition modes. Ga sites modulate the electronic structure of cyano sites, enhancing photoinduced charge separation and synergistically boosting peroxidase-like activity. Inhibition kinetics reveal that thiol-containing drugs exhibit distinct mixed inhibition modes by targeting different active sites, with inhibition markedly enhanced under light. Leveraging these differential inhibition patterns, we developed a Ga-CN-based sensor array, integrating machine learning for precise antithyroid drug screening, facilitating early drug discovery.