P50 Small molecule probes for detection and quantification of hydrogen sulfide

Abstract

Background Hydrogen sulfide (H 2 S), although historically known for its toxicity and rotten egg smell, is now accepted as one of three biosynthetic gaseous transmitters along with nitric oxide (NO) and carbon monoxide (CO). In addition to its proposed role in numerous signaling pathways in the cardiovascular and nervous system, biological hydrogen sulfide levels correlate highly with different disease states including Down syndrome, Alzheimer’s disease, and diabetes. Despite the emerging importance of H 2 S, few biologically-compatible methods are available for its detection or quantification. Based on these needs, our research group is focused on the development and application of new methods for biological H 2 S detection and quantification. Methods Hydrogen sulfide is both a strong reductant and a potent nucleophile. Based on these two chemical properties, we have developed fluorescent probes based on H 2 S-mediated reduction of nitro (RNO 2 ) and azido (RN 3 ) functional groups and colorimetric probes based on the nucleophilic attack of H 2 S on activated electrophiles. Results The developed fluorescent probes based on H 2 S-mediated reduction of nitro or azido groups are selective for H 2 S over other reactive sulfur, oxygen, nitrogen, species (RSONs) including cysteine, glutathione, α-lipoic acid, nitric oxide, hydrogen peroxide, sulfite, and thiosulfate. Furthermore, the developed probes can detect H 2 S in the presence of physiological (10 mM) concentrations of glutathione, thus highlighting the selectivity of these probes. As a proof of concept, the developed probes were demonstrated to detect exogenous H 2 S in live cells. Similarly, the developed colorimetric probes for H 2 S are selective for H 2 S over other reactive species and amino acids. Based on the unique off–on-off colorimetric detection by these probes, estimation of H 2 S levels in aqueous samples is possible. Summary Our group has developed highly-selective fluorescent probes for H2S that are selective for H 2 S over other reactive sulfur, oxygen, and nitrogen species. Similarly, we have developed colorimetric methods for H 2 S detection and quantification.