One-step synthesis of an activatable hydrogen selenide donor with fluorescence-monitored release and its application in cells

As an essential element for life, selenium plays an important role in the synthesis of selenium-containing proteins, signal transduction and the maintenance of redox balance. In addition, selenides have received increasing attention for their demonstrated anticancer effects. In the human body, hydrogen selenide (H₂Se) is considered to be a hub for the biotransformation of selenium-containing molecules. Therefore, elucidating the physiological roles of H₂Se also further promotes the biological application of various selenium-containing compounds, all of which are inseparable from the use of H₂Se donors. However, controlled-release H₂Se donors are very limited and suffer from difficulties in monitoring H₂Se release. This has not only been a major hindrance limiting H₂Se research, but also indicates that the preparation of excellent H₂Se donors is challenging. To this end, we have designed and synthesized a one-step synthetic, conditionally activated donor IN-D capable of visualizing H₂Se release via fluorescence enhancement. IN-D was obtained by the reaction of 2-naphthyl isocyanide and selenium powder, which released H₂Se and fluorescence signals upon triggering by cysteine, enabling real-time monitoring of the flux of H₂Se release. To the best of our knowledge, this is the first donor that has successfully enabled direct visualization of H₂Se release fluxes in a biological environment. We believe that the development of IN-D will not only provide a promising tool for biomedical research on H₂Se, but also provide inspiration for the development of fluorescence-generating H₂Se donors.