Alkylsulfenyl thiocarbonates: precursors to hydropersulfides potently attenuate oxidative stress

Abstract

The recent discovery of the prevalence of hydropersulfides (RSSH) species in biological systems suggests their potential roles in cell regulatory processes. However, the reactive and transient nature of RSSH makes their study difficult, and dependent on the use of donor molecules. Herein, we report alkylsulfenyl thiocarbonates as a new class of RSSH precursors that efficiently release RSSH under physiologically relevant conditions. RSSH release kinetics from these precursors are tunable through electronic modification of the thiocarbonate carbonyl group's electrophilicity. In addition, these precursors also react with thiols to release RSSH with a minor amount of carbonyl sulfide (COS). Importantly, RSSH generation by these precursors protects against oxidative stress in H9c2 cardiac myoblasts. Furthermore, we demonstrate the ability of these precursors to increase intracellular RSSH levels.