Hydrolysis-Based Small-Molecule Hydrogen Selenide (H2Se) Donors for Intracellular H2Se Delivery

• DOI: 10.1021/jacs.1c09525
• Publication Date: 2021-11-10T00:22:11Z
• Authors: Turner D. Newton; Sarah G. Bolton; Arman C. Garcia; Julie E. Chouinard; Stephen L. Golledge; Lev N. Zakharov; Michael D. Pluth
• Keywords: Selenide; Bioinorganic chemistry

Hydrogen selenide (H2Se) is a central metabolite in the biological processing of selenium for incorporation into selenoproteins, which play crucial antioxidant roles systems. Despite being integral to proper physiological function, this reactive species (RSeS) has received limited attention. We recently reported an early example H2Se donor (TDN1042) that exhibited slow, sustained release through hydrolysis. Here we expand technology based on P═Se motif develop cyclic-PSe compounds with increased rates hydrolysis and function well-defined mechanisms as monitored by 31P 77Se NMR spectroscopy. In addition, report colorimetric method reaction NBD-Cl generate NBD-SeH (λmax = 551 nm), can be used detect free H2Se. Furthermore, use TOF-SIMS (time flight secondary ion mass spectroscopy) demonstrate these donors are cell permeable technique spatial mapping intracellular Se content after delivery. Moreover, reduce endogenous oxygen (ROS) levels. Taken together, work expands toolbox sets stage future focused activity beneficial applications related bioinorganic RSeS.