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S-Nitrosothiol

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Structure of an S–nitrosothiol. R denotes some organic group.

In organic chemistry, S-nitrosothiols, also known as thionitrites, are organic compounds or functional groups containing a nitroso group attached to the sulfur atom of a thiol.[1] S-Nitrosothiols have the general formula R−S−N=O, where R denotes an organic group.

S-Nitrosothiols have received much attention in biochemistry because they serve as donors of both the nitrosonium ion NO and of nitric oxide and thus best rationalize the chemistry of NO-based signaling in living systems, especially related to vasodilation.[2] Red blood cells, for instance, carry an essential reservoir of S-nitrosohemoglobin and release S-nitrosothiols into the bloodstream under low-oxygen conditions, causing the blood vessels to dilate.[3]

In biochemistry

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Originally suggested by Ignarro to serve as intermediates in the action of organic nitrates, endogenous S-nitrosothiols were discovered by Stamler and colleagues (S-nitrosoalbumin in plasma and S-nitrosoglutathione in airway lining fluid) and shown to represent a main source of NO bioactivity in vivo. More recently, S-nitrosothiols have been implicated as primary mediators of protein S-nitrosylation, the oxidative modification of cysteine thiol that provides ubiquitous regulation of protein function.

S-nitrosothiols are composed of small molecules, peptides and proteins. The addition of a nitroso group to a sulfur atom of an amino acid residue of a protein is known as S-nitrosylation or S-nitrosation. This is a reversible process and a major form of posttranslational modification of proteins.[4]

S-Nitrosylated proteins (SNO-proteins) serve to transmit nitric oxide (NO) bioactivity and to regulate protein function through enzymatic mechanisms analogous to phosphorylation and ubiquitinylation: SNO donors target specific amino acids motifs; post-translational modification leads to changes in protein activity, protein interactions, or subcellular location of target proteins; all major classes of proteins can undergo S-nitrosylation, which is mediated by enzymes that add (nitrosylases) and remove (denitrosylases) SNO from proteins, respectively. Accordingly, nitric oxide synthase (NOS) activity does not directly lead to SNO formation, but rather requires an additional class of enzymes (SNO synthases), which catalyze denovo S-nitrosylation. NOSs ultimately target specific Cys residues for S-nitrosylation through conjoint actions of SNO-synthases and transnitrosylases (transnitrosation reactions), which are involved in virtually all forms of cell signaling, ranging from regulation of ion channels and G-protein coupled reactions to receptor stimulation and activation of nuclear regulatory protein.[5][6]

Structure and reactions

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The prefix "S" indicates that the NO group is attached to sulfur. The S-N-O angle is near 114°, reflecting the influence of the lone pair of electrons on nitrogen.[7]

S-Nitrosothiols may arise from condensation from nitrous acid and a thiol:[8]

RSH HONO → RSNO H2O

Other methods for their synthesis. They can be synthesized from N2O3 and tert-butyl nitrite (tBuONO) are commonly used.[9][10][11][12]

Once formed, these deeply colored compounds are often thermally unstable with respect to formation of the disulfide and nitric oxide:[13]

2 RSNO → RSSR 2 NO

That equation reverses under irradiation.[14] Nitrosothiols also nitrosate amines in a similarly radical reaction:[13]

4 RSNO  2R′2NH → 2 R′2NNO  2 (RS)2  N2O  H2O

S-Nitrosothiols release nitrosonium ions (NO ) upon treatment with acids:

RSNO H → RSH NO

and they can transfer nitroso groups to other nucleophiles, including other thiols:

RSNO R'SH → RSH R'SNO

These reactions are, however, generally slow equilibria and require distillatory removal of the product to proceed.[15]

In the Saville reaction, mercury replaces the nitrosonium ion:

2 RSNO Hg → Hg(SR)2 2 NO

Detection

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S-Nitrosothiols can be detected with UV-vis spectroscopy.

Examples

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S-Nitrosoglutathione

References

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  1. ^ "Nitroso" IUPAC nomenclature
  2. ^ Zhang Y.; Hogg, N. (2005). "S-Nitrosothiols: cellular formation and transport". Free Radical Biology and Medicine. 38 (7): 831–838. doi:10.1016/j.freeradbiomed.2004.12.016. PMID 15749378.
  3. ^ Diesen, Diana L.; Douglas T. Hess; Jonathan S. Stamler (2008). "Hypoxic vasodilation by red blood cells: evidence for an S-nitrosothiol-based signal". Circulation Research. 103 (5): 545–53. doi:10.1161/CIRCRESAHA.108.176867. PMC 2763414. PMID 18658051.
  4. ^ Ernst van Faassen; Anatoly Fyodorovich Vanin (7 May 2007). Radicals for life: the various forms of nitric oxide. Elsevier. pp. 204–. ISBN 978-0-444-52236-8. Retrieved 5 September 2011.
  5. ^ Gaston, B.; et al. (2003). "S-Nitrosylation Signaling in Cell Biology". Molecular Interventions. 3 (5): 253–63. doi:10.1124/mi.3.5.253. PMID 14993439.
  6. ^ Gaston, B.; et al. (2006). "S-Nitrosothiol Signaling in Respiratory Biology". American Journal of Respiratory and Critical Care Medicine. 173 (11): 1186–1193. doi:10.1164/rccm.200510-1584PP. PMC 2662966. PMID 16528016.
  7. ^ Arulsamy, N.; Bohle, D. S.; Butt, J. A.; Irvine, G. J.; Jordan, P. A.; Sagan, E. (1999). "Interrelationships between Conformational Dynamics and the Redox Chemistry of S-Nitrosothiols". Journal of the American Chemical Society. 121 (30): 7115–7123. doi:10.1021/ja9901314.
  8. ^ Wang, P. G.; Xian, M.; Tang, X.; Wu, X.; Wen, Z.; Cai, T.; Janczuk, A. J. (2002). "Nitric Oxide Donors: Chemical Activities and Biological Applications". Chemical Reviews. 102 (4): 1091–1134. doi:10.1021/cr000040l. PMID 11942788.
  9. ^ Byler, D. M.; Susi, H (1981). "Vibrational spectra and normal coordinate analysis of methyl thionitrite and isotopic analogs". J. Mol. Struct. 77 (1–2): 25–36. Bibcode:1981JMoSt..77...25B. doi:10.1016/0022-2860(81)85264-7.
  10. ^ Goto, K.; Hino, Y.; Kawashima, T.; Kaminaga, M.; Yano, E.; Yamamoto, G.; Takagi, N.; Nagase, S. (2000). "Synthesis and crystal structure of a stable S-nitrosothiol bearing a novel steric protection group and of the corresponding S-nitrothiol". Tetrahedron Letters. 41 (44): 8479–8483. doi:10.1016/S0040-4039(00)01487-8.
  11. ^ Bartberger, M.D.; Houk, K.N.; Powell, S.C.; Mannion, J.D.; Lo, K.Y.; Stamler, J.S.; Toone, E.J. (2000). "Theory, Spectroscopy, and Crystallographic Analysis ofS-Nitrosothiols: Conformational Distribution Dictates Spectroscopic Behavior". J. Am. Chem. Soc. 122 (24): 5889–5890. doi:10.1021/ja994476y.
  12. ^ Field, L.; Dilts, R.V.; Ravichandran, R.; Lenhert, P.G.; Carnahan, G.E. (1978). "An unusually stable thionitrite from N-acetyl-D,L-penicillamine; X-ray crystal and molecular structure of 2-(acetylamino)-2-carboxy-1,1-dimethylethyl thionitrite". J. Chem. Soc. Chem. Commun. (6): 249–250. doi:10.1039/c39780000249.
  13. ^ a b Williams, D. L. H. (1988). Nitrosation. Cambridge, UK: Cambridge University. pp. 174–175, 180. ISBN 0-521-26796-X.
  14. ^ Williams 1988, p. 182.
  15. ^ Williams 1988, p. 181.
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