Kinetic Insights into Hydrogen Sulfide (H2S) Delivery from Caged-Carbonyl Sulfide (COS) Isomeric Donor Platforms

摘要

Hydrogen sulfide (H2S) 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 H2S in biology, researchers often use H2S donors to mimic enzymatic H2S synthesis or to provide increased H2S levels under specific circumstances. Aligned with the need for new broad and easily-modifiable platforms for H2S donation, we report here the preparation and H2S 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 H2S by the ubiquitous enzyme carbonic anhydrase. Each donor is designed to release COS/H2S after the activation of a trigger by activation by hydrogen peroxide (H2O2). In addition to providing a broad palette of new, H2O2-responsive donor motifs, we also demonstrate the H2O2 dose-dependent COS/H2S release from each donor core, establish that release profiles can be modified by structural modifications, and compare COS/H₂S release rates and efficiencies from isomeric core structures. Supporting our experimental investigations, we also provide computational insights into the potential energy surfaces for COS/H₂S release from each platform. In addition, we also report initial investigations into dithiocarbamate cores, which release H₂S directly upon H₂O₂-mediated activation. As a whole, the insights on COS/H₂S release gained from these investigations provide a foundation for the expansion of the emerging area of responsive COS/H₂S donors systems.