Hydrogen Sulfide Donors Activated by Reactive Oxygen Species.

Hydrogen sulfide (H2 S) exhibits promising protective effects in many (patho)physiological processes, as evidenced by recent reports using synthetic H2 S donors in different biological models. Herein, we report the design and evaluation of compounds denoted PeroxyTCM, which are the first class of reactive oxygen species (ROS)-triggered H2 S donors. These donors are engineered to release carbonyl sulfide (COS) upon activation, which is quickly hydrolyzed to H2 S by the ubiquitous enzyme carbonic anhydrase (CA). The donors are stable in aqueous solution and do not release H2 S until triggered by ROS, such as hydrogen peroxide (H2 O2 ), superoxide (O2- ), and peroxynitrite (ONOO- ). We demonstrate ROS-triggered H2 S donation in live cells and also demonstrate that PeroxyTCM-1 provides protection against H2 O2 -induced oxidative damage, suggesting potential future applications of PeroxyTCM and similar scaffolds in H2 S-related therapies.