Tunable Light-Activated Platform for Controlled Hydrogen Sulfide Release with Tracking.

Hydrogen sulfide (HS) 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 HS'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 HS 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 HS by carbonic anhydrase, and the entire reaction progression was monitored by changes in fluorescence signals. Furthermore, this HS-releasing platform is suitable for conjugation with active pharmaceutical ingredients, facilitating the creation of HS-releasing hybrid prodrugs. Collectively, this novel class of HS donor not only provides valuable tool for HS-related research but also holds significant potential as therapeutic agent.