Self-Immolative Thiocarbamates Provide Access to Triggered H(2)S Donors and Analyte Replacement Fluorescent Probes

[Image: see text] Hydrogen sulfide (H(2)S) is an important biological signaling molecule, and chemical tools for H(2)S delivery and detection have emerged as important investigative methods. Key challenges in these fields include developing donors that are triggered to release H(2)S in response to stimuli and developing probes that do not irreversibly consume H(2)S. Here we report a new strategy for H(2)S donation based on self-immolation of benzyl thiocarbamates to release carbonyl sulfide, which is rapidly converted to H(2)S by carbonic anhydrase. We leverage this chemistry to develop easily modifiable donors that can be triggered to release H(2)S. We also demonstrate that this approach can be coupled with common H(2)S-sensing motifs to generate scaffolds which, upon reaction with H(2)S, generate a fluorescence response and also release caged H(2)S, thus addressing challenges of analyte homeostasis in reaction-based probes.