Chemical probes for molecular imaging and detection of hydrogen sulfide and reactive sulfur species in biological systems

Abstract

Hydrogen sulfide (H2S), a gaseous species produced by both bacteria and higher eukaryotic organisms, including mammalian vertebrates, has attracted attention in recent years for its contributions to human health and disease. H2S has been proposed as a cytoprotectant and gasotransmitter in many tissue types, including mediating vascular tone in blood vessels as well as neuromodulation in the brain. The molecular mechanisms dictating how H2S affects cellular signaling and other physiological events remain insufficiently understood. Furthermore, the involvement of H2S in metal-binding interactions and formation of related RSS such as sulfane sulfur may contribute to other distinct signaling pathways. Owing to its widespread biological roles and unique chemical properties, H2S is an appealing target for chemical biology approaches to elucidate its production, trafficking, and downstream function. In this context, reaction-based fluorescent probes offer a versatile set of screening tools to visualize H2S pools in living systems. Three main strategies used in molecular probe development for H2S detection include azide and nitro group reduction, nucleophilic attack, and CuS precipitation. Each of these approaches exploit the strong nucleophilicity and reducing potency of H2S to achieve selectivity over other biothiols. In addition, a variety of methods have been developed for the detection of other reactive sulfur species (RSS), including sulfite and bisulfite, as well as sulfane sulfur species and related modifications such as S-nitrosothiols. Access to this growing chemical toolbox of new molecular probes for H2S and related RSS sets the stage for applying these developing technologies to probe reactive sulfur biology in living systems.

Near-Infrared Fluorescence Probe for in Situ Detection of Superoxide Anion and Hydrogen Polysulfides in Mitochondrial Oxidative Stress

“…Accumulated evidences suggest that hydrogen sulfide (H 2 S, a member of RSS) plays essential roles in regulating the intracellular redox status and fundamental signaling processes. 4,5 However, recently interests are focused on physiological functions of another member of RSS: hydrogen polysulfides (H 2 S n , n > 1).…”

In situ quantification and evaluation of ClO−/H2S homeostasis in inflammatory gastric tissue by applying a rationally designed dual-response fluorescence probe featuring a novel H+-activated mechanism

“…Meanwhile, many elaborate probes have also been designed for the quantification of RSS in blood, tissues, cells, and organelles [19][20][21][22][23][24][25][26] Thus a phenyl-C=N-N-R group was designed as the fast reporter for ClO -. On the other hand, in situ determination of endogenous H 2 S in tissue is still a challenge, because it requires the rapid and sensitive response.…”

H2S Donors in creation of innovative drugs

“…Показана можливість взаємодії H 2 S з окисне-ними тіолами, генеруючи реактивні персульфіди, а також з іонами металів, що входять до складу багатьох ензимів [46]. Дослідження останніх років показали, що H 2 S бере участь у регуляції вісцеральної ноцицепції і соматичній гіпералгезії у мишей.…”