Self-Immolative Thiocarbamates Provide Access to Triggered H₂S Donors and Analyte Replacement Fluorescent Probes

Hydrogen sulfide (H₂S) is an important biological signaling molecule, and chemical tools for H₂S delivery and detection have emerged as important investigative methods. Key challenges in these fields include developing donors that are triggered to release H₂S in response to stimuli and developing probes that do not irreversibly consume H₂S. Here we report a new strategy for H₂S donation based on self-immolation of benzyl thiocarbamates to release carbonyl sulfide, which is rapidly converted to H₂S by carbonic anhydrase. We leverage this chemistry to develop easily modifiable donors that can be triggered to release H₂S. We also demonstrate that this approach can be coupled with common H₂S-sensing motifs to generate scaffolds which, upon reaction with H₂S, generate a fluorescence response and also release caged H₂S, thus addressing challenges of analyte homeostasis in reaction-based probes