Isomerization peroxynitrous acid

It should be noted that Reaction (4) is not a one-stage process.) Both free radical N02 and highly reactive peroxynitrite are the initiators of lipid peroxidation although the elementary stages of initiation by these compounds are not fully understood. (Crow et al. [45] suggested that trans-ONOO is protonated into trans peroxynitrous acid, which is isomerized into the unstable cis form. The latter is easily decomposed to form hydroxyl radical.) Another possible mechanism of prooxidant activity of nitric oxide is the modification of unsaturated fatty acids and lipids through the formation of active nitrated lipid derivatives. 

FIGURE 12. Transition structure for the isomerization of peroxynitrous acid to nitric acid optimized at the B3LYP/6-311- -G(d,p) level of theory. Classical reaction barrier, TS total energy and imaginary frequency (vectors represented by the arrows) are 40.8 kcalmoL (with respect to ds-GS HO—ONO), —280.86143 au and 690i cm, respectively... 

Isomerization of trans-peroxynitrite anion and trans-peroxynitrous acid to nitrate through the putative hydroxyl radical-like intermediates. 

Ray, J. D. (1962). Heat of isomerization of peroxynitrite to nitrate and kinetics of isomerization of peroxynitrous acid to nitric acid. J. Inorg. Nttcleotide Chem. 24, 1159-1162. 

The first-order reaction rate constant for the isomerization of peroxynitrous acid to nitrate is 4.5 s 1 at 37°C therefore, at pH 7.4 and at 37°C the half-life of the peroxynitrite/peroxynitrous acid couple (let both these species be referred to as peroxynitrite for the sake of brevity) is less than 1 s. The reaction mechanism of peroxynitrite decomposition was a subject of controversy. Primarily proposed was that peroxynitrous acid decomposes by homolysis, producing two strong oxidants hydroxyl radical and nitrous dioxide (B15) ... 

Peroxynitrite is converted to its protonated form, peroxynitrous acid (ONOOH) with a pRa of 6.8. This acid form undergoes isomerization to form nitrate anion with a rate constant of 1.3 s [Eq. (12)]. Peroxynitrite is a powerful oxidant and during oxidation reactions with substrates, it undergoes homolysis, generating two powerful oxidants OH and NO2 radicals (-28%) [Eq. (13)], which can mediate oxidation, nitration and nitrosation reactions leading to impaired function of biomolecules. 

One report of the rates of the isomerization of peroxynitrous acid to nitric acid involved interpretation of the results of a calorimetric method of estimation of residual peroxynitrite (from the heat of decomposition). Two other reports are in substantial agreement. From experiments with alkaline solutions, the isomerisation was found to be first order in OONO" and in hydrogen ion. At 25 °C and fi = 0.25, k is 5.7 x 10 l.rnole. sec and the activation energy 12.0 kcal.mole Quite irreproducible behaviour was found with solutions more alkaline than pH 9. There may well be difficulty with buffers and also with contaminants as yet undisclosed. 

Oxidations by peroxynitrite can take place either directly by ground-state peroxynitrous acid, ONOOH, or indirectly by ONOOH where ONOOH is an activated form of peroxynitrous acid (Goldstein et al. 1996). In the direct oxidation pathway the reaction is first order in peroxynitrite and first order in substrate, and the oxidation yield approaches 100%. In the indirect oxidation pathway the reaction is first order in peroxynitrite and zero order in substrate. In the presence of sufficient concentrations of a substrate that reacts by the indirect oxidation pathway, about 50-60% of the ONOOH directly isomerize to nitric acid, and about 40-50% of the ONOOH is converted to ONOOH. The involvement of hydroxyl radicals in indirect oxidations by peroxynitrite is ruled out on the basis of kinetics and oxidation yields. 

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