S-Nitrosothiol

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Structure of an S-nitrosothiol. R denotes some organic group. RSNO.png
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.

Contents

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

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

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

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

Examples

S-Nitrosoglutathione Nitrosoglutathione.svg
S-Nitrosoglutathione

Related Research Articles

In chemistry, a disulfide is a compound containing a R−S−S−R′ functional group or the S2−
2 anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups.

<span class="mw-page-title-main">Thiol</span> Any organic compound having a sulfanyl group (–SH)

In organic chemistry, a thiol, or thiol derivative, is any organosulfur compound of the form R−SH, where R represents an alkyl or other organic substituent. The −SH functional group itself is referred to as either a thiol group or a sulfhydryl group, or a sulfanyl group. Thiols are the sulfur analogue of alcohols, and the word is a blend of "thio-" with "alcohol".

<span class="mw-page-title-main">Xanthine oxidase</span> Class of enzymes

Xanthine oxidase is a form of xanthine oxidoreductase, a type of enzyme that generates reactive oxygen species. These enzymes catalyze the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid. These enzymes play an important role in the catabolism of purines in some species, including humans.

<span class="mw-page-title-main">Nitric oxide synthase</span> Class of enzymes

Nitric oxide synthases (NOSs) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule. It helps modulate vascular tone, insulin secretion, airway tone, and peristalsis, and is involved in angiogenesis and neural development. It may function as a retrograde neurotransmitter. Nitric oxide is mediated in mammals by the calcium-calmodulin controlled isoenzymes eNOS and nNOS. The inducible isoform, iNOS, involved in immune response, binds calmodulin at physiologically relevant concentrations, and produces NO as an immune defense mechanism, as NO is a free radical with an unpaired electron. It is the proximate cause of septic shock and may function in autoimmune disease.

Organosulfur chemistry is the study of the properties and synthesis of organosulfur compounds, which are organic compounds that contain sulfur. They are often associated with foul odors, but many of the sweetest compounds known are organosulfur derivatives, e.g., saccharin. Nature is abound with organosulfur compounds—sulfur is vital for life. Of the 20 common amino acids, two are organosulfur compounds, and the antibiotics penicillin and sulfa drugs both contain sulfur. While sulfur-containing antibiotics save many lives, sulfur mustard is a deadly chemical warfare agent. Fossil fuels, coal, petroleum, and natural gas, which are derived from ancient organisms, necessarily contain organosulfur compounds, the removal of which is a major focus of oil refineries.

<span class="mw-page-title-main">Nitrosation and nitrosylation</span> Process of converting organic compounds into nitroso derivatives

Nitrosation and nitrosylation are two names for the process of converting organic compounds or metal complexes into nitroso derivatives, i.e., compounds containing the R−NO functionality. The synonymy arises because the R-NO functionality can be interpreted two different ways, depending on the physico-chemical environment:

The nitrosonium ion is NO+, in which the nitrogen atom is bonded to an oxygen atom with a bond order of 3, and the overall diatomic species bears a positive charge. It can be viewed as nitric oxide with one electron removed. This ion is usually obtained as the following salts: NOClO4, NOSO4H (nitrosylsulfuric acid, more descriptively written ONSO3OH) and NOBF4. The ClO−4 and BF−4 salts are slightly soluble in acetonitrile CH3CN. NOBF4 can be purified by sublimation at 200–250 °C and 0.01 mmHg (1.3 Pa).

<span class="mw-page-title-main">Nitroso</span> Class of functional groups with a –N=O group attached

In organic chemistry, nitroso refers to a functional group in which the nitric oxide group is attached to an organic moiety. As such, various nitroso groups can be categorized as C-nitroso compounds, S-nitroso compounds, N-nitroso compounds, and O-nitroso compounds.

Gasotransmitters is a class of neurotransmitters. The molecules are distinguished from other bioactive endogenous gaseous signaling molecules based on a need to meet distinct characterization criteria. Currently, only nitric oxide, carbon monoxide, and hydrogen sulfide are accepted as gasotransmitters. According to in vitro models, gasotransmitters, like other gaseous signaling molecules, may bind to gasoreceptors and trigger signaling in the cells.

<span class="mw-page-title-main">Nitroxyl</span> Chemical compound

Nitroxyl or azanone is the chemical compound HNO. It is well known in the gas phase. Nitroxyl can be formed as a short-lived intermediate in the solution phase. The conjugate base, NO−, nitroxide anion, is the reduced form of nitric oxide (NO) and is isoelectronic with dioxygen. The bond dissociation energy of H−NO is 49.5 kcal/mol (207 kJ/mol), which is unusually weak for a bond to the hydrogen atom.

<span class="mw-page-title-main">Nitrosyl chloride</span> Chemical compound

Nitrosyl chloride is the chemical compound with the formula NOCl. It is a yellow gas that is commonly encountered as a component of aqua regia, a mixture of 3 parts concentrated hydrochloric acid and 1 part of concentrated nitric acid. It is a strong electrophile and oxidizing agent. It is sometimes called Tilden's reagent, after William A. Tilden, who was the first to produce it as a pure compound.

<span class="mw-page-title-main">Sulfenic acid</span> Organosulfur compound of the form R–SOH

In chemistry, a sulfenic acid is an organosulfur compound and oxoacid with the general formula R−S−OH. It is the first member of the family of organosulfur oxoacids, which also include sulfinic acids and sulfonic acids, respectively. The base member of the sulfenic acid series with R = H is hydrogen thioperoxide.

<i>S</i>-Nitroso-<i>N</i>-acetylpenicillamine Chemical compound

S-Nitroso-N-acetylpenicillamine (SNAP) is the organosulfur compound with the formula ONSC(CH3)2CH(NHAc)CO2H. It is a green solid.

In organic chemistry, the Baudisch reaction is a process for the synthesis of nitrosophenols using metal ions. Although the products are of limited value, the reaction is of historical interest as an example of metal-promoted functionalization of aromatic substrates.

<span class="mw-page-title-main">Reactive nitrogen species</span>

Reactive nitrogen species (RNS) are a family of antimicrobial molecules derived from nitric oxide (•NO) and superoxide (O2•−) produced via the enzymatic activity of inducible nitric oxide synthase 2 (NOS2) and NADPH oxidase respectively. NOS2 is expressed primarily in macrophages after induction by cytokines and microbial products, notably interferon-gamma (IFN-γ) and lipopolysaccharide (LPS).

<span class="mw-page-title-main">Formaldehyde dehydrogenase</span> Enzyme

In enzymology, a formaldehyde dehydrogenase (EC 1.2.1.46) is an enzyme that catalyzes the chemical reaction

Biological functions of nitric oxide are roles that nitric oxide plays within biology.

In biochemistry, S-nitrosylation is the covalent attachment of a nitric oxide group to a cysteine thiol within a protein to form an S-nitrosothiol (SNO). S-Nitrosylation has diverse regulatory roles in bacteria, yeast and plants and in all mammalian cells. It thus operates as a fundamental mechanism for cellular signaling across phylogeny and accounts for the large part of NO bioactivity.

<i>S</i>-Nitrosoglutathione Chemical compound

S-Nitrosoglutathione (GSNO) is an endogenous S-nitrosothiol (SNO) that plays a critical role in nitric oxide (NO) signaling and is a source of bioavailable NO. NO coexists in cells with SNOs that serve as endogenous NO carriers and donors. SNOs spontaneously release NO at different rates and can be powerful terminators of free radical chain propagation reactions, by reacting directly with ROO• radicals, yielding nitro derivatives as end products. NO is generated intracellularly by the nitric oxide synthase (NOS) family of enzymes: nNOS, eNOS and iNOS while the in vivo source of many of the SNOs is unknown. In oxygenated buffers, however, formation of SNOs is due to oxidation of NO to dinitrogen trioxide (N2O3). Some evidence suggests that both exogenous NO and endogenously derived NO from nitric oxide synthases can react with glutathione to form GSNO.

<span class="mw-page-title-main">Jonathan Stamler</span> English-American physician and biochemist

Jonathan Solomon Stamler is an English-born American physician and scientist. He is known for his discovery of protein S-nitrosylation, the addition of a nitric oxide (NO) group to cysteine residues in proteins, as a ubiquitous cellular signal to regulate enzymatic activity and other key protein functions in bacteria, plants and animals, and particularly in transporting NO on cysteines in hemoglobin as the third gas in the respiratory cycle.

References

  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. 1 2 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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