NO/HS "Crosstalk" Reactions. The Role of Thionitrites (SNO) and Perthionitrites (SSNO).

The redox chemistry of HS with NO and other oxidants containing the NO group is discussed on a mechanistic basis because of the expanding interest in their biological relevance, with an eye open to the chemical differences of HS and thiols RSH. We focus on the properties of two "crosstalk" intermediates, SNO (thionitrite) and SSNO (perthionitrite, nitrosodisulfide) based in the largely controversial status on their identity and chemistry in aqueous/nonaqueous media, en route to the final products NO, NO, NHOH/NH, and S. Thionitrous acid, generated either in the direct reaction of NO + HS or through the transnitrosation of RSNO's (nitrosothiols) with HS at pH 7.4, is best described as a mixture of rapidly interconverting isomers, {(H)SNO}. It is reactive in different competitive modes, with a half-life of a few seconds at pH 7.4 for homolytic cleavage of the N-S bond, and could be deprotonated at pH values of up to ca. 10, giving SNO, a less reactive species than {(H)SNO}. The latter mixture can also react with HS, giving HNO and HS (hydrogen disulfide), a S(sulfane)-transfer reagent toward {(H)SNO}, leading to SSNO, a moderately stable species that slowly decomposes in aqueous sulfide-containing solutions in the minute-hour time scale, depending on [O]. The previous characterization of HSNO/SNO and SSNO is critically discussed based on the available chemical and spectroscopic evidence (mass spectrometry, UV-vis, N NMR, Fourier transform infrared), together with computational studies including quantum mechanics/molecular mechanics molecular dynamics simulations that provide a structural and UV-vis description of the solvatochromic properties of -SSNO acting as an electron donor in water, alcohols, and aprotic acceptor solvents. In this way, SSNO is confirmed as the elusive "yellow intermediate" (I) emerging in the aqueous crosstalk reactions, in contrast with its assignment to polysulfides, HS. The analysis extends to the coordination abilities of {(H)SNO}, SNO, and SSNO into heme and nonheme iron centers, providing a basis for best unraveling their putative specific signaling roles.