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.