Bioinorganic Chemistry of Hydrogen Sulfide: Detection, Delivery, and Interactions with Metalloproteins

Abstract

Hydrogen sulfide (H 2 S) has received significant attention in the past two decades for its role in biological processes. Despite numerous studies on the biological activity of this gas, the specific nature of the interaction between H 2 S and metalloproteins and biologically relevant metal ions remains largely unknown. The current understanding of the chemical biology of H 2 S with metalloproteins and enzymes is discussed herein. The utility of inorganic complexes as tools for the detection and delivery of H 2 S under biologically relevant conditions is also discussed.

Interactions of reactive sulfur species with metalloproteins

“…At high levels, sulfide irreversibly inhibits the activity of CcO and blocks cellular respiration. At low concentrations, sulfide can donate an electron to CcO and support mitochondrial energy production [ 40 ]. Thirdly, in penta-coordinated heme proteins, the type of protein chain residues surrounding the active site nearby the distal binding position has a pivotal role.…”

“…The third important area where sulfide exhibits its biological effects is via extensive interactions with metalloproteins [ 27 , 39 , 40 ]. Metalloproteins require one or more metal ions for the development of their proper structure and functionality, and they account for 30–40% of the human proteome [ 41 , 42 ].…”

“…Transition metal centers of borderline acid character according to the hard and soft acids and bases principle (Fe(II), Cu(II), Zn(II)) constitute the primary sites of sulfide-metal biochemistry via complex formation and/or electron transfer reactions [ 39 , 40 , 55 ]. It is noteworthy that due to the ease of sulfur – metal reactions, reactive sulfur species alleviate heavy metal toxicity, as reported for methylmercury or cadmium, among others [ 56 , 57 ].…”

Metal Coordination Complexes as Therapeutic Agents for Ischemia-Reperfusion Injury

“…Most commonly known as a toxic gas with a rotten egg smell, H 2 S has recently emerged as the third gasotransmitter, joining NO and CO in this important biological regulatory role . Over the past two decades, endogenous H 2 S and related polysulfides (H 2 S n ), produced via different enzymatic processes, have been implicated in a wide variety of biological processes, including cancer progression, cellular metabolism, neurological regulation, , cell death pathways, and the regulation of cardiovascular function . Three H 2 S-generating enzymes, cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST), are the primary producers of endogenous H 2 S and play a vital role in the aforementioned processes .…”

“…Most commonly known as a toxic gas with a rotten egg smell, H 2 S has recently emerged as the third gasotransmitter, joining NO and CO in this important biological regulatory role. 84 Over the past two decades, endogenous H 2 S and related polysulfides (H 2 S n ), produced via different enzymatic processes, 85 have been implicated in a wide variety of biological processes, 86 including cancer progression, 87 cellular metabolism, 88 neurological regulation, 89,90 cell death pathways, 91 and the regulation of…”