Nitrosation nitric oxide

Nitrosation. Nitric oxide (NO) reacts very slowly with primary or secondary amines unless oxygen is present to convert NO into N2O3 and N2O4. These two oxides of nitrogen convert primary and secondary amines into N-nitrosamines rapidly in either neutral or alkaline aqueous solutions. This reaction is insensitive to the basicity of the amine. Nitrogen oxides are common pollutants and some N-nitrosamines e.g., N-nitrosodimethylamine) are known to be carcinogens."... 

Nonaqueous Systems In nonaqueous (nonpolar) solvent systems, nitrosatlon also proceeds. In these solvents, alpha-tocopherol acts as a lipid soluble blocking agent in much the same fashion as ascorbic acid functions in the aqueous phase. Alpha-tocopherol reacts with a nitrosating agent and reduces it to nitric oxide. At the same time, alpha-tocopherol is oxidized to tocoquinone, which is the first oxidation product of vitamin E and also a normal metabolite in vivo. 

Indeed, given an improperly designed or understood system, a blocking agent, like ascorbic acid, could be catalytic toward nitrosamine formation. For example, if the source of nitrosatlng agent is nitrite ion and the susceptible amine is in the lipid phase, conceivably ascorbic acid could cause the rapid reduction of nitrite ion to nitric oxide which could migrate to the lipid phase. Subsequent oxidation of NO to NO in the lipid phase could cause nitrosation. 

D. L. H. Williams Nitrosation Reactions and the Chemistry of Nitric Oxide , Elsevier, Amsterdam, 2004. 

Nitric oxide is a physiological substrate for mammalian peroxidases [myeloperoxide (MPO), eosinophil peroxide, and lactoperoxide), which catalytically consume NO in the presence of hydrogen peroxide [60], On the other hand, NO does not affect the activity of xanthine oxidase while peroxynitrite inhibits it [61]. Nitric oxide suppresses the inactivation of CuZnSOD and NO synthase supposedly via the reaction with hydroxyl radicals [62,63]. On the other hand, SOD is able to modulate the nitrosation reactions of nitric oxide [64]. 

Reactions of the bioregulatory agent nitric oxide in oxygenated aqueous media determination of the kinetics for oxidation and nitrosation by intermediates generated in the NO/02 reaction, Chem. Res. Toxicol. 6 (1993), p. 23-27... 

In these reactions, the nitrosating species is N203, which is formed by oxidation of NO (Eqns. 9.1 and 9.2) and acts as a donor of NO+ (Eqn. 9.3), while also undergoing competitive hydrolysis (Eqn. 9.4). Thus, effective ni-trosation requires sufficiently high concentration of the thiol to compete efficiently with hydrolysis of N203. Note that nitric oxide can also be oxidized by other oxidants (e.g., ferric hemoproteins, see below) to form the nitroso-nium ion (NO+), which then reacts rapidly with thiolates (Eqns. 9.5 and 9.6) ... 

Nitrous acid catalysis also takes place in the nitration of such compounds (naphthalene) that are unable to undergo nitrosation on the given conditions or whose nitrosation proceeds slower than nitration. As accepted, the nitrosonium ion is formed from HNOj in acid media. The nitrosonium ion oxidizes an aromatic substrate into a cation-radical and transforms into nitric oxide. The latter reduces nitronium cation to nitrogen dioxide that gives a a-complex with the aromatic cation-radical ... 

Nitrogen oxides. Nitric oxide (NO) itself, has been shown to be a poor nitrosating agent (28), probably because it is unable to abstract an amino-H atom to generate the dialkyl-amino radical, which might then combine with further NO. However, the presence of even a small amount of air results in complete conversion, presumably via oxidation of NO to NO2. Nitrosation by NO is catalyzed by metal salts, such as Znl2, CuCl, and CUSO4. The metal catalyzed reaction is inhibited in acid or aqueous media (29). 

Nitric oxide rapidly reacts with transition metals, which have stable oxidation states differing by one electron (see Chapters 2 and 3). Nitric oxide is unusual in that it reacts with both the ferric (Fe " ) and ferrous forms (Fe " ) of iron. TTie unpaired electron of nitric oxide is partially transferred to the metal forming a principally ionic bond. Complexes of ferric iron with nitric oxide are called nitrosyl compounds and will nitrosate (add an NO group) many compounds, while reducing the iron to the ferrous state (Wade and Castro, 1990). 

Although much of the biological literature focuses on nitrosating reactions of nitric oxide, chemically nitric oxide is a moderate one-electron oxidant, making formation of nitroxyl anion feasible under physiological conditions. The reduction potential to reduce nitric oxide to nitroxyl anion is +0.39 V, whereas it requires +1.2 V to oxidize nitric oxide to nitrosonium ion. Nitrosating reactions of nitric oxide are often mediated by conversion of nitric oxide to another nitrogen oxide species or by direct reaction with transition metals (Wade and Castro, 1990). 

Because of the high 1.2 V potential for oxidation, nitric oxide cannot directly nitrosate organic molecules without a cofactor to accept the unpaired electron. Clearly, the following reaction to form a nitrosothiol from nitric oxide is unbalanced unless there is a strong electron acceptor. 

The nitrosation of phenol and cresols in buffer solutions involves a diffusion-controlled C-nitrosation followed by rate-limiting proton loss. /r-Crcsol is much less reactive than the other substrates.79 Nitrosation in trifluoroacetic acid or in acetic-sulfuric acid mixtures is regioselective (e.g. 4-nitroso-m-xylene is fonned from m-xylene) and possible non-selective nitrous acid-catalysed nitration can be eliminated by purging reaction solutions with nitric oxide.80... 

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