Direct hydrogen selenide (HSe) release from activatable selenocarbamates.

Hydrogen selenide (HSe) is a possible bioregulator, potential gasotransmitter, and important precursor in biological organoselenium compound synthesis. Early tools for HSe research have benefitted from available mechanistic understanding of analogous small molecules developed for detecting or delivering HS. A now common approach for HS delivery is the use of small molecule thiocarbamates that can be engineered to release COS, which is quickly converted to HS by carbonic anhydrase. To expand our understanding of the chemical underpinnings that enable HSe 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 HSe directly with concomitant isocyanate formation rather than by the intermediate release of COSe. This reaction mechanism for direct HSe release is further supported by computational investigations that identify a ΔΔ ∼ 25 kcal mol between the HSe and COSe release pathways in the absence of protic solvent. This work highlights fundamentally new approaches for HSe release from small molecules and advances the understanding of reactivity differences between reactive sulfur and selenium species.