Ruthenium Coordination Complexes as Tools for Studying Biological Hydrogen Sulfide

With the support of the Chemistry of Life Processes (CLP) Program in the Division of Chemistry, Justin J. Wilson of Cornell University is developing new tools to study the role of the gas hydrogen sulfide in biological settings and human health. Hydrogen sulfide (H2S) is a small gaseous molecule, sometimes referred to as a gasotransmitter, that is biosynthesized and plays an important role in regulating a number of processes associated with normal and healthy cellular function.

Because hydrogen sulfide is a gas, its controlled delivery to biological systems, in vivo, is challenging. Therefore, a deeper understanding of how this gaseous signaling molecule operates in livings systems is of great interest. This project will develop new chemical tools that can deliver small, biologically relevant amounts of hydrogen sulfide to cells upon activation by selective stimulation.

If successful, these tools will enable researchers to probe the biological relevance and importance of H2S in human health. In addition, this project will develop new educational activities for high school STEM (science, technology, engineering and mathematics) teachers. These activities will be designed to highlight how compounds such as hydrogen sulfide, that can be toxic, may be present in “natural” or “organic” foods at sufficiently low concentrations that do not present a health hazard.

Rather, this compound has a critically important role in human biology and these activities will be designed to educate the public about the fascinating roles of gasotransmitters that are so critical to heathly human biology.

The Wilson research group at Cornell University will design new ruthenium-based hydrogen sulfide-releasing molecules as chemical tools to study the biological roles of the gasotransmitter, hydrogen sulfide (H2S). Hydrogen sulfide regulates a wide range of critical biological processes in eukaryotic cells and is known to elicit therapeutic effects for the management of heart disease, stroke, and cancer.

The direct administration of H2S to biological systems, however, is limited by its gaseous nature and toxicity at high concentrations. To overcome these challenges, researchers have developed easily handled compounds that slowly release this gasotransmitter to study its biological function. These efforts have been focused on organic compounds that are designed to release hydrogen sulfide via uncontrolled hydrolysis, blue or ultraviolet light irradiation, oxidation by reactive oxygen species, enzymatic activity, and reactions with thiols.

The objective of this project is to expand the toolkit of hydrogen sulfide-releasing molecules by developing compounds based on the transition metal ruthenium. By using ruthenium coordination complexes, the Wilson team aims to gain access to hydrogen sulfide-releasing agents that are selectively activated by stimuli that are inaccessible with conventional organic compounds.

Through these efforts, the redox chemistry and photochemistry of ruthenium coordination compounds will be leveraged to make hydrogen sulfide donors that are triggered by chemical reduction and light irradiation, respectively. Lastly, the Wilson group will use these new tools to understand the mechanisms by which hydrogen sulfide can protect against ischemia-reperfusion injury in vitro.

Collectively, this research will expand the toolkit of available hydrogen sulfide donors and will demonstrate their value by applying them to identify new roles for this gasotransmitter in healthy human biology.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.