ROS-Activated Hydrogen Sulfide (H 2 S) Donors Exhibit Protections in H 2 O 2 -Induced Cellular Oxidative Damage

Hydrogen sulfide (H2S) is a well-known antioxidant and exhibits promising protective effects in a variety of physiological and pathological processes. To investigate the chemistry and biology of H2S, people often use H2S releasing agents (known as H2S donors) to mimic enzymatic H2S synthesis. Herein, we report the design and evaluation of a series of caged-carbonyl sulfide (COS) compounds, which comprise the first class of reactive oxygen species (ROS)-triggered H2S donors. These compounds release COS upon activation, which is quickly converted to H2S by the ubiquitous enzyme carbonic anhydrase (CA). These donors are stable in aqueous solution and do not release H2S spontaneously, but rather release H2S in the presence of ROS, such as hydrogen peroxide (H2O2). We demonstrate that such H2S release can be regulated by donor structure modifications and demonstrate that COS/H2S donation can be triggered in live cells by both exogenous and endogenous ROS. In addition, cellular studies indicate that these donors significantly attenuate H2O2-induced cellular oxidative damage, suggesting potential applications of the caged-COS compounds as prodrugs in H2S-related therapies.