Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide.

Peroxynitrite [oxoperoxonitrate(1-), ONOO-] may be formed in vivo from superoxide and nitric oxide. The anion is stable, but the acid (pKa = 6.8) decays to nitrate with a rate of 1.3 s-1 at 25 degrees C. The experimental activation parameters of this process are delta H++ = +18 +/- 1 kcal/mol, delta S++ = +3 +/- 2 cal/(mol.K), and delta G++ = +17 +/- 1 kcal/mol. Peroxynitrite (or its protonated form) oxidizes some compounds such as thiols and thioethers in a biomolecular reaction. The reactions with glutathione and cysteine have activation enthalpies of 10.9 and 9.7 kcal/mol, respectively, which are lower than that of the isomerization reaction. Peroxynitrite reacts with other compounds such as dimethyl sulfoxide and deoxyribose in a unimolecular reaction for which the activation of peroxynitrite is rate-limiting. In theory, activation could involve (1) heterolysis to OH- and NO2+ (delta rxn Gzero' = 13 kcal/mol at pH 7) or (2) homolysis to .OH and .NO2 (delta rxn Gzero = 21 kcal/mol), and these processes also could be involved in the isomerization to nitrate. However, thermodynamic and kinetic considerations indicate that neither process is feasible, although binding to metal ions may reduce the large activation energy associated with heterolysis. An intermediate closely related to the transition state for isomerization of ONOOH to HONO2 may be the strongly oxidizing intermediate responsible for hydroxyl radical-like oxidations mediated by ONOOH. Thus, peroxynitrite reacts with different compounds by at least two distinct mechanisms, and the hydroxyl radical is not involved in either.

[1]  J S Beckman,et al.  Kinetics of superoxide dismutase- and iron-catalyzed nitration of phenolics by peroxynitrite. , 1992, Archives of biochemistry and biophysics.

[2]  J S Beckman,et al.  Peroxynitrite formation from macrophage-derived nitric oxide. , 1992, Archives of biochemistry and biophysics.

[3]  L. Zhu,et al.  Bactericidal activity of peroxynitrite. , 1992, Archives of biochemistry and biophysics.

[4]  J S Beckman,et al.  Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. , 1992, Archives of biochemistry and biophysics.

[5]  V. Anderson,et al.  A stable solid that generates hydroxyl radical upon dissolution in aqueous solutions: reaction with proteins and nucleic acid , 1992 .

[6]  W. Pryor,et al.  Inactivation of alpha 1-proteinase inhibitor by peroxynitrite. , 1992, Chemical research in toxicology.

[7]  W. Pryor,et al.  How far does ozone penetrate into the pulmonary air/tissue boundary before it reacts? , 1992, Free radical biology & medicine.

[8]  D. Blake,et al.  Free radical yields from the homolysis of peroxynitrous acid. , 1992, Free radical biology & medicine.

[9]  H. Sies,et al.  Reversible conversion of nitroxyl anion to nitric oxide by superoxide dismutase. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[10]  F. Murad,et al.  Isoforms of nitric oxide synthase. Characterization and purification from different cell types. , 1991, Biochemical pharmacology.

[11]  M. Salter,et al.  Widespread tissue distribution, species distribution and changes in activity of Ca2+‐dependent and Ca2+‐independent nitric oxide synthases , 1991, FEBS letters.

[12]  C. Nathan,et al.  Purification and characterization of the cytokine-induced macrophage nitric oxide synthase: an FAD- and FMN-containing flavoprotein. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[13]  B. Freeman,et al.  Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. , 1991, Archives of biochemistry and biophysics.

[14]  H. Eizawa,et al.  Purification of nitric oxide synthase from rat macrophages. , 1991, The Journal of biological chemistry.

[15]  S. Snyder,et al.  Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase , 1991, Nature.

[16]  P. Vallance,et al.  Physiological importance of nitric oxide. , 1991, BMJ.

[17]  I. Fidler,et al.  Role of nitric oxide in lysis of tumor cells by cytokine-activated endothelial cells. , 1991, Cancer research.

[18]  C. Nathan,et al.  N omega-hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine. , 1991, The Journal of biological chemistry.

[19]  B. Cheng,et al.  Photolysis of nitric acid in solid argon: the infrared absorption of peroxynitrous acid (HOONO) , 1991 .

[20]  J. Ritter,et al.  Human vascular smooth muscle cells inhibit platelet aggregation when incubated with glyceryl trinitrate: evidence for generation of nitric oxide , 1991, British journal of pharmacology.

[21]  L. Ignarro.  Signal transduction mechanisms involving nitric oxide. , 1991, Biochemical pharmacology.

[22]  J. Garthwaite.  Glutamate, nitric oxide and cell-cell signalling in the nervous system , 1991, Trends in Neurosciences.

[23]  M. Bucher.  EXTRAPOLATION OF THE BORN MODEL TO SOLVATED POINT CHARGES IN AMMONIA AND WATER , 1991 .

[24]  W. Koppenol.  Thermodynamic considerations on the generation of hydroxyl radicals from nitrous oxide--no laughing matter. , 1991, Free radical biology & medicine.

[25]  W. Koppenol.  Oxyradical reactions: from bond‐dissociation energies to reduction potentials , 1990, FEBS letters.

[26]  J. Beckman.  Ischaemic injury mediator , 1990, Nature.

[27]  B. Freeman,et al.  Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[28]  W. Bors,et al.  Reaction of NO with O2-. implications for the action of endothelium-derived relaxing factor (EDRF). , 1990, Free radical research communications.

[29]  D. Stanbury.  Reduction potentials involving inorganic free radicals in aqueous solution , 1990 .

[30]  S Moncada,et al.  Biosynthesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. , 1989, Biochemical pharmacology.

[31]  M. Marletta,et al.  Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. , 1988, Biochemistry.

[32]  F. Rowland,et al.  Isomers of nitric acid and chlorine nitrate , 1988 .

[33]  G. Buxton,et al.  Critical Review of rate constants for reactions of hydrated electrons, hydrogen atoms and hydroxyl radicals (⋅OH/⋅O− in Aqueous Solution , 1988 .

[34]  Koppenol Wh.  The paradox of oxygen: thermodynamics versus toxicity. , 1988 .

[35]  P. Hammer,et al.  Product Analysis of the OH + NO2 + M Reaction , 1987 .

[36]  S. Moncada,et al.  Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor , 1987, Nature.

[37]  M. N. Hughes,et al.  Photolysis of the nitrogen-nitrogen double bond in trioxodinitrate: reaction between triplet oxonitrate(1-) and molecular oxygen to form peroxonitrite , 1986 .

[38]  H. Forman,et al.  Oxidant production and bactericidal activity of phagocytes. , 1986, Annual review of physiology.

[39]  N. Blough,et al.  Reaction of superoxide with nitric oxide to form peroxonitrite in alkaline aqueous solution , 1985 .

[40]  H. Schwarz,et al.  Equilibrium between hydroxyl radicals and thallium(II) and the oxidation potential of hydroxyl(aq) , 1984 .

[41]  W. Pryor,et al.  Reaction of cumene with ozone to form cumyl hydrotrioxide and the kinetics of decomposition of cumyl hydrotrioxide , 1983 .

[42]  W. Pryor,et al.  Oxidation of thiols by nitric oxide and nitrogen dioxide: synthetic utility and toxicological implications , 1982 .

[43]  R. Morse,et al.  Electron paramagnetic resonance studies of nitrosyl ferrous heme complexes. Determination of an equilibrium between two conformations. , 1980, The Journal of biological chemistry.

[44]  S. Benson,et al.  Thermochemistry and kinetics of ozonation reactions , 1980 .

[45]  W. L. Jolly,et al.  Chemical syntheses with a quenched flow reactor. Hydroxytrihydroborate and peroxynitrite , 1974 .

[46]  W. Pryor,et al.  Reactions of radicals. XXVI. On the use of activation parameters as a test for concerted decomposition of initiators , 1971 .

[47]  L. Mahoney.  Evidence for the formation of hydroxyl radicals in the isomerization of pernitrous acid to nitric acid in aqueous solution , 1970 .

[48]  P. Moore,et al.  Kinetics and mechanism of the formation and decay of peroxynitrous acid in perchloric acid solutions , 1970 .

[49]  R. Powell,et al.  Kinetics of decomposition of peroxynitrous acid , 1969 .

[50]  M. N. Hughes,et al.  The chemistry of pernitrites. Part I. Kinetics of decomposition of pernitrous acid , 1968 .

[51]  D. R. Rosseinsky,et al.  Electrode Potentials and Hydration Energies. Theories and Correlations , 1965 .

[52]  G. Petriconi,et al.  Formation and Decomposition of Alkaline ‘Pernitrite’ , 1964, Nature.

[53]  W. A. Guillory,et al.  Infrared Absorption by Peroxy-Nitrogen Trioxide Free Radical in the Gas Phase , 1963 .

[54]  J. D. Ray.  Heat of isomerization of peroxynitrite to nitrate and kinetics of isomerization of peroxynitrous acid to nitric acid , 1962 .

[55]  E. Halfpenny,et al.  169. The nitration and hydroxylation of aromatic compounds by pernitrous acid , 1952 .

[56]  E. Halfpenny,et al.  168. Pernitrous acid. The reaction between hydrogen peroxide and nitrous acid, and the properties of an intermediate product , 1952 .

[57]  J. Kirkwood,et al.  Theory of Solutions of Molecules Containing Widely Separated Charges with Special Application to Zwitterions , 1934 .

[58]  K. Gleu,et al.  Die Einwirkung von Ozon auf Alkaliazid. Persalpetrige Säure I , 1929 .

[59]  I. Trifonow.  Anwendung der Persalpetersäure für analytische Zwecke , 1922 .