Peroxynitrite decomposition

It has been suggested that there are three major pathways for peroxynitrite to react with various substrates. With a pK value for peroxynitrite equal to 6.8 [103], peroxynitrite exists in the ionized or nonionized form depending on pH. Furthermore, the reactivity of peroxynitrite depends on its cis- and trans-conformations. Correspondingly, the following mechanisms for peroxynitrite decomposition have been proposed ... 

The effect of buffer anions on peroxynitrite decomposition. As the concentration of formate is increased, the rate of peroxynitrite decomposition increases but reaches a plateau at high concentrations. The maximum rate depends on the pH. 

Apparent first-order rate constants for peroxynitrite decomposition in various buffers versus pH. When peroxynitrite is fully protonated at acidic pH, the decomposition rate is constant. The breakpoint in the curve identifies the pK, of peroxynitrite since a larger fraction present as an anion slows the rate of decomposition. In 50 mM potassium phosphate, the apparent pK, is at 6.8 and is not affected by temperatute (Koppenol, 1993). The rate of decomposition is not affected hy DMSO, mannitol, or ethanol. As shown in Fig. 28, many buffers can slightly accelerate the decomposition of peroxynitrite and the rate of decomposition reaches a maximum at high buffer concentrations. When these maximal rates are plotted as a function of pH, peroxynitrite exhibits a second pK, of approximately 8.0. 

Augusto, O., Gatti, R. M., and Radi, R. (1994). Spin-trapping studies of peroxynitrite decomposition and of 3-morpholinosydnonimine N-ethylcarbamide autooxidation. Arch. Biochem. Biophys. 310, 118-125. 

Merenyi G, Lind J, Goldstein S, Czapski G (1999) Mechanism and thermochemistry of peroxynitrite decomposition in water. J Phys Chem A 103 5685-5691 Merenyi G, Lind J, Goldstein S (2002a) Thermochemical properties of a-hydroxy-alkoxyl radicals in aqueous solution. J Phys Chem A 106 11127-11129 Merenyi G, Lind J, Goldstein S (2002b) The rate of homolysis of adducts of peroxynitrite to the C=0 double bond. J Am Chem Soc 124 40-48... 

Richeson CE, Mulder P, Bowry VW, Ingold KU (1998) The complex chemistry of peroxynitrite decomposition new insights. J Am Chem Soc 120 7211-7219 Rodrigues GS, MadkourSA, Weinstein LH (1996) Genotoxic activity of ozone in tradescantia. Environ Exp Bot 36 45-50... 

The cadmium(II) complex corresponding to 9 (M = Cd n = 2) was the first texaphyrin made [6], This aromatic expanded porphyrin was found to differ substantially from various porphyrin complexes and it was noted that its spectral and photophysical properties were such that it might prove useful as a PDT agent. However, it was also appreciated that the poor aqueous solubility and inherent toxicity of this particular metal complex would likely preclude its use in vivo [29-31], Nonetheless, the coordination chemistry of texaphyrins such as 9 was soon generalized to allow for the coordination of late first row transition metal (Mn(II), Co(II), Ni(II), Zn (II), Fe(III)) and trivalent lanthanide cations [26], This, in turn, opened up several possibilities for rational drag development. For instance, the Mn(II) texaphyrin complex was found to act as a peroxynitrite decomposition catalyst [32] and is being studied currently for possible use in treating amyotrophic lateral sclerosis. This work, which is outside the scope of this review, has recently been summarized by Crow [33],... 

Another "OH generating reaction is peroxynitrite decomposition to hydroxyl radical and nitrogen dioxide (see sect. 1.12). Also, actions of ionizing radiation and ultrasounds yielding water molecule decomposition are additional sources of "OH. The hydroxyl radical is probably the main reactive species in the so-called metal-catalyzed oxidation systems (or mixed-function oxidation systems) used in experiments where ascorbate and metal ions are employed (though formation of other products such as high-valency iron species ferryl Fe+4 or perferryl Fe+5 forms cannot be excluded) (N2, S50). 

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) ... 

Metalloporphyrins, characterized by a redox-active transitional metal coordinated to a cyclic porphyrin core ligand, mitigate oxidative/nitrosative stress in biological systems. Side-chain substitutions tune redox properties of metalloporphyrins to act as potent superoxide dismutase mimetics, peroxynitrite decomposition catalysts, and redox regulators of transcription factor function. Metalloporphyrins are efficacious in AD models [538],... 

Pacher P, Liaudet L, Bai P, Mabley JG, Kaminski PM, Virdg L, Deb A, Szabo E, Ungvdri Z, Wolin MS, Groves JT, Szabo C (2003) Potent metalloporphyrin peroxynitrite decomposition catalyst protects against the development of doxorubicin-induced cardiac dysfunction. Circulation 107 896-904... 

Hunt, J.A., J. Lee, and J.T. Groves (1997). Amphiphilic peroxynitrite decomposition catalysts in liposomal assemblies. Chem. Biol. 4, 845-858. 

Shimanovich, R. and J.T. Groves (2001). Mechanisms of peroxynitrite decomposition catalyzed by fetmps, a bioactive sulfonated iron porphyrin. Arch. Biochem. Biophys. 387, 307-317. 

Szabo, C., J.G. Mabley, S.M. Moeller, R. Shimanovich, P. Pacher, L. Viiag et al. (2002). Pathogenic role of peroxynitrite in the development of diabetes and diabetic vascular complications Studies with FP15, a novel, potent peroxynitrite decomposition catalyst. Mol Med. 8, 571-580. 

Peroxynitrite is a highly reactive oxidant produced by the combination of NO and O2 -. There are indications that it may contribute to cell death and tissue injury in a number of human diseases, including arthritis (Kaur and Halliwell 1994), sepsis (SzABO et al. 1995), inflammatory bowel disease (Rachmilewitz et al. 1993) and stroke (Oury et al. 1993). Peroxynitrite decomposition catalysts (Salvemini et al. 1998) may represent a unique class of antiinflammatory agents. 

Mn(III)TMPyP is a manganese porphyrin that acts as a superoxide dismutase (SOD) mimetic and peroxynitrite decomposition catalyst (Han et al., 2001). SOD mimetics described to date are unstable and are capable of catalyzing undesired side reactions in addition to the dismutation of the superoxide radical. Mn(III)TMPyP is an SOD mimetic with increased stability to pH and hydrogen peroxide. The rate constants for superoxide dismutation and peroxynitrite decomposition are 3.9 X 10 M s and... 

Cuzzocrea, S., Misko, T.P., Costantino, G., Mazzon, E., Micali, A., Caputi, A.P., Macarthur, H., and Salvemini, D. (2000). Beneficial effects of peroxynitrite decomposition catalyst in a rat model of splanchnic artery occlusion and reperfusion. FASEB J. 14, 1061-1072. 

J. P. Crow. Manganese and iron porphyrins catalyze peroxynitrite decomposition and simultaneously increase nitration and oxidant yield inplications for their use as peroxynitrite scavengers in vivo. Arch.Biochem.Biophys. 371 (l) 41-52,1999. 

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