Does Perthionitrite (SSNO^–) Account for Sustained Bioactivity of NO? A (Bio)chemical Characterization

Abstract

Hydrogen sulfide (H2S) and nitric oxide (NO) are important signaling molecules that regulate several physiological functions. Understanding the chemistry behind their interplay is important for explaining these functions. The reaction of H2S with S-nitrosothiols to form the smallest S-nitrosothiol, thionitrous acid (HSNO), is one example of physiologically relevant cross-talk between H2S and nitrogen species. Perthionitrite (SSNO(-)) has recently been considered as an important biological source of NO that is far more stable and longer living than HSNO. In order to experimentally address this issue here, we prepared SSNO(-) by two different approaches, which lead to two distinct species: SSNO(-) and dithionitric acid [HON(S)S/HSN(O)S]. (H)S2NO species and their reactivity were studied by (15)N NMR, IR, electron paramagnetic resonance and high-resolution electrospray ionization time-of-flight mass spectrometry, as well as by X-ray structure analysis and cyclic voltammetry. The obtained results pointed toward the inherent instability of SSNO(-) in water solutions. SSNO(-) decomposed readily in the presence of light, water, or acid, with concomitant formation of elemental sulfur and HNO. Furthermore, SSNO(-) reacted with H2S to generate HSNO. Computational studies on (H)SSNO provided additional explanations for its instability. Thus, on the basis of our data, it seems to be less probable that SSNO(-) can serve as a signaling molecule and biological source of NO. SSNO(-) salts could, however, be used as fast generators of HNO in water solutions.

Reactions between nitrosopersulfide and heme proteins

“…However, another group has suggested that SSNO − is too unstable to be of any physiological relevance [22]. We find that SSNO − is relatively stable in the absence of heme-proteins.…”

“…Our data suggest that NO is not efficiently formed from SSNO − in the presence of ligated heme, but is formed when there is a vacant heme, indicating a direct reaction between the vacant heme and SSNO − is required to get NO from SSNO − . Furthermore, ferriheme is more efficient at acquiring NO from SSNO − than ferrous heme [22]. We also find that in the presence of heme-containing proteins, SSNO − does not yield HNO.…”

“…It also was shown to decay completely within 10 minutes when exposed to water [22]. However, in our hands, SSNO − is very stable under anaerobic conditions and decays slowly under aerobic conditions (half life of about 40 minutes) in aqueous buffer (Fig.…”

“…In previous work the compound SSNO − was shown to be unstable in the presence of light [22], decaying within a minute of exposure to 55 mW of light at 470 nm. It also was shown to decay completely within 10 minutes when exposed to water [22].…”

“…sGC is a heme containing protein and direct interaction between SSNO − and sGC cannot be ruled out. Although some believe SSNO − is physiologically relevant, still others suggest that SSNO − is too unstable to be physiologically relevant [20, 22]. In this study, we sought to determine the stability and spontaneous reactivity of SSNO − in the presence of heme-containing proteins.…”