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.