Direct hydrogen selenide (H(2)Se) release from activatable selenocarbamates

Hydrogen selenide (H(2)Se) is a possible bioregulator, potential gasotransmitter, and important precursor in biological organoselenium compound synthesis. Early tools for H(2)Se research have benefitted from available mechanistic understanding of analogous small molecules developed for detecting or delivering H(2)S. A now common approach for H(2)S delivery is the use of small molecule thiocarbamates that can be engineered to release COS, which is quickly converted to H(2)S by carbonic anhydrase. To expand our understanding of the chemical underpinnings that enable H(2)Se delivery, we investigated whether selenocarbamates undergo similar chemistry to release carbonyl selenide (COSe). Using both light- and hydrolysis-activated systems, we demonstrate that unlike their lighter thiocarbamate congeners, selenocarbamates release H(2)Se directly with concomitant isocyanate formation rather than by the intermediate release of COSe. This reaction mechanism for direct H(2)Se release is further supported by computational investigations that identify a ΔΔG(‡) ∼ 25 kcal mol(−1) between the H(2)Se and COSe release pathways in the absence of protic solvent. This work highlights fundamentally new approaches for H(2)Se release from small molecules and advances the understanding of reactivity differences between reactive sulfur and selenium species.