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

摘要

Hydrogen sulfide (H_2S) 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 H_2S in biology, researchers often use H_2S donors to mimic enzymatic H_2S synthesis or to provide increased H_2S levels under specific circumstances. Aligned with the need for new broad and easily modifiable platforms for H_2S donation, we report here the preparation and H_2S 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 H_2S by the ubiquitous enzyme carbonic anhydrase. Each donor is designed to release COS/H_2S after the activation of a trigger by activation by hydrogen peroxide (H_2O_2). In addition to providing a broad palette of new, H_2O_2-responsive donor motifs, we also demonstrate the H_2O_2 dose-dependent COS/H_2S release from each donor core, establish that release profiles can be modified by structural modifications, and compare COS/H_2S release rates and efficiencies from isomeric core structures. Supporting our experimental investigations, we also provide computational insights into the potential energy surfaces for COS/H_2S release from each platform. In addition, we also report initial investigations into dithiocarbamate cores, which release H_2S directly upon H_2O_2-mediated activation. As a whole, the insights on COS/H_2S release gained from these investigations provide a foundation for the expansion of the emerging area of responsive COS/H_2S donor systems.