An Examination of Chemical Tools for Hydrogen Selenide Donation and Detection

Hydrogen selenide (H₂Se) is an emerging biomolecule of interest with similar properties to that of other gaseous signaling molecules (i.e., gasotransmitters that include nitric oxide, carbon monoxide, and hydrogen sulfide). H₂Se is enzymatically generated in humans where it serves as a key metabolic intermediate in the production of selenoproteins and other selenium-containing biomolecules. However, beyond its participation in biosynthetic pathways, its involvement in cellular signaling or other biological mechanisms remains unclear. To uncover its true biological significance, H₂Se-specific chemical tools capable of functioning under physiological conditions are required but lacking in comparison to those that exist for other gasotransmitters. Recently, researchers have begun to fill this unmet need by developing new H₂Se-releasing compounds, along with pioneering methods for selenide detection and quantification. In combination, the chemical tools highlighted in this review have the potential to spark groundbreaking explorations into the chemical biology of H₂Se, which may lead to its branding as the fourth official gasotransmitter.