Work

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

Year: 2017

Type: article

Abstract: Hydrogen sulfide (H 2 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 H 2 S in biology, researchers often use H 2 S donors to mimic enzymatic H 2 S synthesis or to provide increased H 2 S levels under specific circumstances. Aligned with the need for new broad and easily modifiable platforms for H 2 S donation, we report here the preparation and H 2 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 H 2 S by the ubiquitous enzyme carbonic anhydrase. Each donor is designed to release COS/H 2 S after the activation of a trigger by activation by hydrogen peroxide (H 2 O 2 ). In addition to providing a broad palette of new, H 2 O 2 -responsive donor motifs, we also demonstrate the H 2 O 2 dose-dependent COS/H 2 S release from each donor core, establish that release profiles can be modified by structural modifications, and compare COS/H 2 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/H 2 S release from each platform. In addition, we also report initial investigations into dithiocarbamate cores, which release H 2 S directly upon H 2 O 2 -mediated activation. As a whole, the insights on COS/H 2 S release gained from these investigations provide a foundation for the expansion of the emerging area of responsive COS/H 2 S donor systems.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.7b09527

Authors: Yu Zhao, Hillary A. Henthorn, Michael D. Pluth

Institution: University of Oregon

Language: English

Topic: Sulfur Compounds in Biology

Subfield: Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Science Foundation, Alfred P. Sloan Foundation, Camille and Henry Dreyfus Foundation, National Institute of General Medical Sciences

Awards: Hydrogen Sulfide and Carbonyl Sulfide Delivery for Biological Applications, MRI: Acquisition of High Sensitivity 500 MHz NMR for the University of Oregon CAMCOR NMR Facility, MRI-R2: Acquisition of an Applied Computational Instrument, G938714593