Phenacylselenoesters allow facile selenium transfer and hydrogen selenide generation

Abstract

Hydrogen selenide (H₂Se) is a precursor to several selenium-containing biomolecules and is emerging as an important redox-active species in biology, with yet to be completely characterized roles. Tools that reliably generate H₂Se are key to achieving a better understanding of selenium biology. Here, we report the design, synthesis and evaluation of phenacylselenoesters as sources of H₂Se. These compounds are prepared in two steps from commercial compounds, some are crystalline solids, and all are stable during storage. In the presence of esterase and a thiol in pH 7.4 buffer, these compounds produce H₂Se, with half-lives of 5–20 min. We developed a colorimetric assay for the detection of gaseous H₂Se by trapping it as zinc selenide (ZnSe), which is then converted to lead selenide (PbSe), which serves as a convenient visual indicator for this gas. The major organic products that are formed in nearly quantitative yields are relatively benign ketones and carboxylic acids. We provide evidence for these donors producing a thioselenide, a key intermediate in biological selenium metabolism. Finally, we compared sulfur and selenium transfer, both critical processes in cells. Phenacylthiol is relatively stable to cleavage by a thiol, and requires a sulfurtransferase enzyme to produce a persulfide and H₂S. By contrast, the selenium analogue reacted with a thiol in the absence of this enzyme to produce H₂Se. This result underscores the greater lability of the C–Se bond as compared with a C–S bond, and may have implications in biological selenium transfer. Together, phenacylselenoesters are easy to prepare, stable and generate H₂Se under mild and biocompatible conditions. We anticipate that these will be valuable additions to the growing selenium redox toolbox.