A thiol-activated near-infrared fluorescent H₂S donor for visualizing H₂S release and its applications

Hydrogen sulfide (H₂S), a critical endogenous signaling molecule, is involved in diverse physiological processes, and H₂S donors have emerged as promising therapeutic agents. While organic donors address the uncontrolled release limitations of inorganic counterparts, most thiol-activated systems depend exclusively on cysteine (Cys), risking cellular thiol imbalance. To overcome this limitation, we developed AD-SH, a novel benzopyran salts-based NIR fluorescent H₂S donor responsive to multiple biothiols. AD-SH exhibits high selectivity and sensitivity toward all intracellular biothiols (e.g., cysteine, glutathione, and homocysteine) without preferentially depleting a single Cys. Importantly, its near-infrared (NIR) fluorescence enables real-time tracking and visualization of H₂S release. With excellent biocompatibility, photostability, and in vivo imaging performance in mice, AD-SH demonstrates its strong potential for live-cell imaging and dynamic H₂S release tracking.