H₂S donors with optical responses

Reactive sulfur species, including hydrogen sulfide (H₂S), are important biological mediators and play key roles in different pathophysiological conditions. Small molecules that release H₂S on demand, often referred to as "H₂S donors," constitute a key investigative tool for H₂S-related research. A significant challenge, however, is correlating the rate of H₂S release from such donors in complex systems with biological outcomes, because release rates are commonly perturbed by different biological environments. In this chapter, we outline an approach to use H₂S donors that provide a fluorescent response upon H₂S release to address this problem. These compounds leverage the intermediate release of carbonyl sulfide (COS), which is quickly converted to H₂S by the endogenous enzyme carbonic anhydrase (CA), to provide activatable donors with an optical response. The described donors are activated by biological thiols and provide a fluorescence response that correlates directly with H₂S delivery, which allows for delivered H₂S levels to be measured in real time by fluorescence techniques.