Activatable Small-Molecule Hydrogen Sulfide Donors

This is the authors' abstract. We don't add key points for this paper.

Significance: Hydrogen sulfide (H₂S) is an important biological signaling molecule involved in many physiological processes. These diverse roles have led researchers to develop contemporary methods to deliver H₂S under physiologically relevant conditions and in response to various stimuli. Recent Advances: Different small-molecule donors have been developed that release H₂S under various conditions. Key examples include donors activated in response to hydrolysis, to endogenous species, such as thiols, reactive oxygen species, and enzymes, and to external stimuli, such as photoactivation and bio-orthogonal chemistry. In addition, an alternative approach to release H₂S has utilized the catalyzed hydrolysis of carbonyl sulfide (COS) by carbonic anhydrase to generate libraries of activatable COS-based H₂S donors. Critical Issues: Small-molecule H₂S donors provide important research and pharmacological tools to perturb H₂S levels. Key needs, both in the development and in the use of such donors, include access to new donors that respond to specific stimuli as well as donors with well-defined control compounds that allow for clear delineation of the impact of H₂S delivery from other donor byproducts. Future Directions: The abundance of reported small-molecule H₂S donors provides biologists and physiologists with a chemical toolbox to ask key biological questions and to develop H₂S-related therapeutic interventions. Further investigation into different releasing efficiencies in biological contexts and a clear understanding of biological responses to donors that release H₂S gradually (e.g., hours to days) versus donors that generate H₂S quickly (e.g., seconds to minutes) is needed.