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

Hydrogen sulfide (H2S) is increasingly recognized for its critical roles 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 originating from the detached PPG moiety. 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 tools for H2S-related research but also holds significant potential as therapeutic agents.