Nitric oxide, reaction mechanisms with electron transfer reactions

This statement does not mean, however, that the mechanism of diazotization was completely elucidated with that breakthrough. More recently it was possible to test the hypothesis that, in the reaction between the nitrosyl ion and an aromatic amine, a radical cation and the nitric oxide radical (NO ) are first formed by a one-electron transfer from the amine to NO+. Stability considerations imply that such a primary step is feasible, because NO is a stable radical and an aromatic amine will form a radical cation relatively easily, especially if electron-donating substituents are present. As discussed briefly in Section 2.6, Morkovnik et al. (1988) found that the radical cations of 4-dimethylamino- and 4-7V-morpholinoaniline form the corresponding diazonium ions with the nitric oxide radical (Scheme 2-39). 

At present, new developments challenge previous ideas concerning the role of nitric oxide in oxidative processes. The capacity of nitric oxide to oxidize substrates by a one-electron transfer mechanism was supported by the suggestion that its reduction potential is positive and relatively high. However, recent determinations based on the combination of quantum mechanical calculations, cyclic voltammetry, and chemical experiments suggest that °(NO/ NO-) = —0.8 0.2 V [56]. This new value of the NO reduction potential apparently denies the possibility for NO to react as a one-electron oxidant with biomolecules. However, it should be noted that such reactions are described in several studies. Thus, Sharpe and Cooper [57] showed that nitric oxide oxidized ferrocytochrome c to ferricytochrome c to form nitroxyl anion. These authors also proposed that the nitroxyl anion formed subsequently reacted with dioxygen, yielding peroxynitrite. If it is true, then Reactions (24) and (25) may represent a new pathway of peroxynitrite formation in mitochondria without the participation of superoxide. 

Peroxyl radicals are not only ones, which are able to react with ubihydroquinones. Poderoso et al. [245] showed that the short-chain ubihydroquinones Q0 and Q2 are oxidized by nitric oxide with the rate constants of 0.49 x 104 and 1.6x 1041 mol-1 s 1, respectively. The reaction apparently proceeded by one-electron transfer mechanism because the formation of intermediate semiquinone radicals has been registered. 

Despite intense study of the chemical reactivity of the inorganic NO donor SNP with a number of electrophiles and nucleophiles (in particular thiols), the mechanism of NO release from this drug also remains incompletely understood. In biological systems, both enzymatic and non-enzymatic pathways appear to be involved [28]. Nitric oxide release is thought to be preceded by a one-electron reduction step followed by release of cyanide, and an inner-sphere charge transfer reaction between the ni-trosonium ion (NO+) and the ferrous iron (Fe2+). Upon addition of SNP to tissues, formation of iron nitrosyl complexes, which are in equilibrium with S-nitrosothiols, has been observed. A membrane-bound enzyme may be involved in the generation of NO from SNP in vascular tissue [35], but the exact nature of this reducing activity is unknown. 

The reaction of phenols with nitrous acid gives the ortho- and para-nitroso products, which are formed through a neutral dienone intermediate, the proton loss from the latter being the rate-limiting step" " . It has been shown that the nitrous acid can act as a catalyst for the formation of the nitro derivatives. Thus the conventional preparation of nitro compounds by the oxidation of nitroso compounds may be replaced by methods using an electron-transfer pathway in certain cases. In the latter method, the phenoxide reacts with nitrosonium ion to give the phenoxy radical and nitric oxide radical. The nitric oxide radical is in equilibrium with the nitronium radical by reaction with nitronium ion. The reaction of the phenoxy radical with the nitroninm radical resnlts in the formation of the ortho- and para-mixo prodncts" . Leis and coworkers carried ont kinetic stndies on the reaction of phenolate ions with alkyl nitrites and fonnd that the initially formed product is the 0-nitrite ester, which evolves by a complex mechanism to give the ortho-and the para-nitro products". ... 

The short life of NO and its low concentration in biological systems make the measurement of this molecule a challenging analytical problem. Among several methods (biochemical assays, UV-Visible spectroscopy, chemiluminescence, EPR) electrochemical methods are considered to be the most suitable for in situ detection of NO in biological milieu. " Generally, the electrochemical oxidation of nitric oxide on solid electrodes proceeds via a two-step (EC mechanism) with an electrochemical reaction as the initial step (heterogenous electron transfer) followed by a chemical reaction. The first electrochemical step is a one-electron transfer from a NO molecule to the electrode residting in the formation of a nitrosonium ion ... 

Although various mechanisms were proposed in order to explain the reactivity behavior of [Ru (NH3)5X] complexes in their reactions with NO, including rate-determining outer-sphere electron-transfer process or rate-determining aquation process, none of them was completely consistent with all kinetic and electrochemical data measured in the study. Therefore, another mechanism was postulated to account for the unusual fast reaction of nitric oxide with a series of investigated Ru(III) ammine complexes (94). It involves a unique combination of associative l%and binding and concerted electron transfer as shown in reaction (7). 

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