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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 15N 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. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is produced endogenously in vivo and has multiple effects on signaling pathways and cell function. Mitochondria can be both an H2S source and sink, and many of the biological effects of H2S relate to its interactions with mitochondria. However, the significance of mitochondrial H2S is uncertain, in part due to the difficulty of assessing changes in its concentration in vivo. Although a number of fluorescent H2S probes have been developed these are best suited to cells in culture and cannot be used in vivo. To address this unmet need we have developed a mitochondria-targeted H2S probe, MitoA, which can be used to assess relative changes in mitochondrial H2S levels in vivo. MitoA comprises a lipophilic triphenylphosphonium (TPP) cation coupled to an aryl azide. The TPP cation leads to the accumulation of MitoA inside mitochondria within tissues in vivo. There, the aryl azido group reacts with H2S to form an aryl amine (MitoN). The extent of conversion of MitoA to MitoN thus gives an indication of the levels of mitochondrial H2S in vivo. Both compounds can be detected sensitively by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the tissues, and quantified relative to deuterated internal standards. Here we describe the synthesis and characterization of MitoA and show that it can be used to assess changes in mitochondrial H2S levels in vivo. As a proof of principle we used MitoA to show that H2S levels increase in vivo during myocardial ischemia. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H 2 S) is produced endogenously in vivo and has multiple effects on signaling pathways and cell function. Mitochondria can be both an H 2 S source and sink, and many of the biological effects of H 2 S relate to its interactions with mitochondria. However, the significance of mitochondrial H 2 S is uncertain, in part due to the difficulty of assessing changes in its concentration in vivo Although a number of fluorescent H 2 S probes have been developed these are best suited to cells in culture and cannot be used in vivo To address this unmet need we have developed a mitochondria-targeted H 2 S probe, MitoA, which can be used to assess relative changes in mitochondrial H 2 S levels in vivo MitoA comprises a lipophilic triphenylphosphonium (TPP) cation coupled to an aryl azide. The TPP cation leads to the accumulation of MitoA inside mitochondria within tissues in vivo There, the aryl azido group reacts with H 2 S to form an aryl amine (MitoN). The extent of conversion of MitoA to MitoN thus gives an indication of the levels of mitochondrial H 2 S in vivo Both compounds can be detected sensitively by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the tissues, and quantified relative to deuterated internal standards. Here we describe the synthesis and characterization of MitoA and show that it can be used to assess changes in mitochondrial H 2 S levels in vivo As a proof of principle we used MitoA to show that H 2 S levels increase in vivo during myocardial ischemia., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)