New Features of the NO/H2S Cross Talk: A Chemical Basis

Abstract

The analysis of the NO + H2S reaction revealed the formation of nitroxyl (HNO), a crucial intermediate with specific signaling abilities as compared to NO. A comparison of the H2S reactivity with other biologically relevant reductants such as ascorbate, hydroquinone, phenols, and thiolates assists the mechanistic study. We also discuss the specificity of the reversible transnitrosation reactions using HS- instead of thiolates RSH, highlighting the role of thionitrous acid HSNO, disulfide HS2-, polysulfides HSx-, and nitrosodisulfide SSNO- anions in putative protein modifications. Controversial characterization and reactivity issues associated with the latter species, either as free or eventually as bound ligands at ironbinding sites, are presented and discussed. The nitroprusside ion and the dinitrosyl iron complexes (DNIC) have been chosen as examples of rich nonheme reactivity for HS-, and diverse heme models and selected enzymes allowed discussing the new possibilities for the NO/H2S cross talk emerging upon coordination. A specific focus has been directed to how HS- might react with NO2-, related to the nonenzymatic production of NO in the vasculature under anoxia and high concentrations of HS-, as well as other metabolic routes of NO2- promoted by iron-heme binding. An insight into the reactivity of HS- toward peroxynitrite also connects with the chemistry of other systems associated with the production of sulfenic species as intermediates. Overall, the chapter highlights the role of sulfur-based S center dot-, S2(center dot-), and hybrid N-S radicals for adequately disclosing the mechanistic issues, both in anaerobic and aerobic conditions, and also provides a discussion on accessible associative routes for HS- and NO/NOx reactants in order to surmount the high activation barriers predicted by unfavorable redox potentials.