Tunable Light‐Activated Platform for Controlled Hydrogen Sulfide Release with Tracking

Hydrogen sulfide (H₂S) is increasingly recognized for its critical role in various physiological and pathological processes. The development of synthetic donors with controllable release profiles is essential for elucidating H₂S's complex involvement in cellular signaling, which remains a challenge. Herein, we report a diverse collection of photocaged N-methylation thiocarbamates and thiocarbonates, designed to explore how electronic properties and the leaving efficiency of payloads affect H₂S release behaviors. These compounds are engineered to release carbonyl sulfide (COS) following the removal of photoprotective group (PPG). The COS could be rapidly converted into H₂S by carbonic anhydrase, and the entire reaction progression was monitored by changes in fluorescence signals. Furthermore, this H₂S-releasing platform is suitable for conjugation with active pharmaceutical ingredients, facilitating the creation of H₂S-releasing hybrid prodrugs. Collectively, this novel class of H₂S donor not only provides valuable tool for H₂S-related research but also holds significant potential as therapeutic agent.