Description:
Hydrogen sulfide (H2S), although generally known for its toxicity and characteristic odor, is now recognized as an important signaling molecule with diverse biological roles. The biological roles of H2S range from roles in angiogenesis to wound healing. In mammals, H2S production is derived primarily from three enzymes: cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopyruvate sulfotransferase (3-MST). The expression of these enzymes in different tissues suggests a broad importance and significance of H2S in the cardiovascular, circulatory, respiratory, urinary, and nervous systems. Abnormal H2S regulation, however, has been associated with hypertension, diabetes, as well as various diseases of mental deficiency including Down's syndrome and Alzheimer's disease. In addition to the pathophysiological conditions associated with H2S misregulation, H2S can also act on specific cellular targets, including heme proteins, cysteine residues on KATP channels, nitric oxide, and other emerging targets.
Complicating investigations into biological H2S, the pKa of H2S (7.0) ensures that both the neutral (H2S) and monoanionic (HS−) forms are present under physiological conditions, leading to significant and unresolved questions on the specific chemistry and recognition events associated with the individual protonation states. Importantly, these recognition events in sulfide transport rely on non-covalent, reversible interactions with HS− rather than metal coordination or interaction with the sulfane-sulfur pool.
Despite the importance of H2S, current methods of detection are plagued by irreversibility, which presents a significant problem in developing chemical tools that provide real-time information on biological processes, suggesting a supramolecular (i.e., reversible) approach to hydrosulfide binding would represent an important contribution.
US Patent # 11,187,690