Kinetic Insights into Hydrogen Sulfide Delivery from Caged-Carbonyl Sulfide Isomeric Donor Platforms.

Hydrogen sulfide (H2 S) is a biologically important small gaseous molecule that exhibits promising protective effects against a variety of physiological and pathological processes. To investigate the expanding roles of H2 S in biology, researchers often use H2 S donors to mimic enzymatic H2 S synthesis or to provide increased H2 S levels under specific circumstances. Aligned with the need for new broad and easily modifiable platforms for H2 S donation, we report here the preparation and H2 S release kinetics from a series of isomeric caged-carbonyl sulfide (COS) compounds, including thiocarbamates, thiocarbonates, and dithiocarbonates, all of which release COS that is quickly converted to H2 S by the ubiquitous enzyme carbonic anhydrase. Each donor is designed to release COS/H2 S after the activation of a trigger by activation by hydrogen peroxide (H2 O2 ). In addition to providing a broad palette of new, H2 O2 -responsive donor motifs, we also demonstrate the H2 O2 dose-dependent COS/H2 S release from each donor core, establish that release profiles can be modified by structural modifications, and compare COS/H2 S release rates and efficiencies from isomeric core structures. Supporting our experimental investigations, we also provide computational insights into the potential energy surfaces for COS/H2 S release from each platform. In addition, we also report initial investigations into dithiocarbamate cores, which release H2 S directly upon H2 O2 -mediated activation. As a whole, the insights on COS/H2 S release gained from these investigations provide a foundation for the expansion of the emerging area of responsive COS/H2 S donor systems.