Abstract
Reactive sulfur species, including hydrogen sulfide (H(2)S), are important biological mediators and play key roles in different pathophysiological conditions. Small molecules that release H(2)S on demand, often referred to as "H(2)S donors," constitute a key investigative tool for H(2)S-related research. A significant challenge, however, is correlating the rate of H(2)S 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 H(2)S donors that provide a fluorescent response upon H(2)S release to address this problem. These compounds leverage the intermediate release of carbonyl sulfide (COS), which is quickly converted to H(2)S 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 H(2)S delivery, which allows for delivered H(2)S levels to be measured in real time by fluorescence techniques.