A General Strategy for Triggerable Donors and Analyte-Replacement Fluorescent Probes of Hydrogen Selenide

Hydrogen selenide (H₂Se) is the precursor for biosynthesis of Se-containing biomolecules and a potential nitric oxide (NO)-like gasotransmitter. Chemical tools for H₂Se delivery and detection are crucial for exploring selenium (Se) biology and medicine. Nevertheless, general platforms for triggerable release of H₂Se remain lacking, and H₂Se fluorescent probes that do not irreversibly consume H₂Se have not yet been reported. Herein, we report a general platform of the fast intramolecular arylthiol-activated arylselenoamides (general FITA) for H₂Se donation and detection. We utilized self-immolative processes to controllable deprotection of an arylthiol for the tandem FITA and developed the first examples of nitroreductase-triggered and reactive oxygen species-triggered H₂Se donors. We leveraged the general FITA motif to construct the first H₂Se analyte-replacement probe which, upon reaction with a H₂Se, generates a fluorescence response and releases a H₂Se, thus underscoring the analyte homeostasis during detection of the H₂Se donation. We anticipate that these well-defined chemistries will promote the development of advanced H₂Se tools with therapeutic potential.