The Yield of Hydroxyl Radical from the Decomposition of Peroxynitrous Acid

Nitric oxide and superoxide, which are produced by several cell types, rapidly combine to form peroxynitrite. This reaction can result in nitric oxide scavenging, and thus mitigation of the biological effects of superoxide. Also, superoxide can trap and hence modulate the effects of nitric oxide; superoxide dismutase, by controlling superoxide levels, therefore can influence the reaction pathways open to nitric oxide. The production of peroxynitrite, however, causes its own sequelae of events: Although neither .NO nor superoxide is a strong oxidant, peroxynitrite is a potent and versatile oxidant that can attack a wide range of biological targets. The peroxynitrite anion is relatively stable, but its acid, peroxynitrous acid (HOONO), rearranges to form nitrate with a half-life of approximately 1 s at pH 7, 37 degrees C. HOONO exists as a Boltzmann distribution of rotamers; at 5-37 degrees C HOONO has an apparent acidity constant, pKa,app, of 6.8. Oxidation reactions of HOONO can involve two-electron processes (such as an SN2 displacement) or a one-electron transfer (ET) reaction in which the substrate is oxidized by one electron and peroxynitrite is reduced. These oxidation reactions could involve one of two mechanisms. The first mechanism is homolysis of HOONO to give HO. and .NO2, which initially are held together in a solvent cage. This caged pair of radicals (the "geminate" pair) can either diffuse apart, giving free radicals that can perform oxidations, or react together either to form nitrate or to reform HOONO (a process called cage return). A large amount of cage return can explain the small entropy of activation (Arrhenius A-factor) observed for the decomposition of HOONO. A cage mechanism also can explain the residual yield of nitrate that appears to be formed even in the presence of high concentrations of all of the scavengers studied to date, since scavengers capture only free HO. and .NO2 and not caged radicals. If the cage mechanism is correct, the rate of disappearance of peroxynitrite be slower in solvents of higher viscosity, and we do not find this to be the case. The second mechanism is that an activated isomer of peroxynitrous acid, HOONO*, can be formed in a steady state. The HOONO* mechanism can explain the inability of hydroxyl radical scavengers to completely block either nitrate formation or the oxidation of substrates such as methionine, since HOONO* would be less reactive, and therefore more selective, than the hydroxyl radical itself.(ABSTRACT TRUNCATED AT 400 WORDS)

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Activation of cytochrome c to a peroxidase compound I-type intermediate by H2O2: relevance to redox signalling in apoptosis

Biochemical Society Symposium ◽

10.1042/bss0710097 ◽

2004 ◽

Vol 71 ◽

pp. 97-106 ◽

Cited By ~ 10

Author(s):

Mark Burkitt ◽

Clare Jones ◽

Andrew Lawrence ◽

Peter Wardman

Keyword(s):

Cytochrome C ◽

Hydroxyl Radical ◽

Redox Regulation ◽

Chemotherapeutic Agents ◽

Tyrosyl Radical ◽

Compound I ◽

Definitive Evidence ◽

Enhanced Production ◽

Physico Chemical

The release of cytochrome c from mitochondria during apoptosis results in the enhanced production of superoxide radicals, which are converted to H2O2 by Mn-superoxide dismutase. We have been concerned with the role of cytochrome c/H2O2 in the induction of oxidative stress during apoptosis. Our initial studies showed that cytochrome c is a potent catalyst of 2′,7′-dichlorofluorescin oxidation, thereby explaining the increased rate of production of the fluorophore 2′,7′-dichlorofluorescein in apoptotic cells. Although it has been speculated that the oxidizing species may be a ferryl-haem intermediate, no definitive evidence for the formation of such a species has been reported. Alternatively, it is possible that the hydroxyl radical may be generated, as seen in the reaction of certain iron chelates with H2O2. By examining the effects of radical scavengers on 2′,7′-dichlorofluorescin oxidation by cytochrome c/H2O2, together with complementary EPR studies, we have demonstrated that the hydroxyl radical is not generated. Our findings point, instead, to the formation of a peroxidase compound I species, with one oxidizing equivalent present as an oxo-ferryl haem intermediate and the other as the tyrosyl radical identified by Barr and colleagues [Barr, Gunther, Deterding, Tomer and Mason (1996) J. Biol. Chem. 271, 15498-15503]. Studies with spin traps indicated that the oxo-ferryl haem is the active oxidant. These findings provide a physico-chemical basis for the redox changes that occur during apoptosis. Excessive changes (possibly catalysed by cytochrome c) may have implications for the redox regulation of cell death, including the sensitivity of tumour cells to chemotherapeutic agents.

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Activities of antioxidant enzymes and nitric oxide synthase, hydroxyl radical and zinc contents in gastric mucosa cells during the recovery of stress-induced stomach lesions

Annales UMCS Pharmacia ◽

10.2478/v10080-008-0036-7 ◽

2008 ◽

Vol 21 (1) ◽

pp. 215-217

Author(s):

Olena Bogdanova ◽

Larysa Kot ◽

Dmytro Lukashov ◽

Ludmyla Ostapchenko

Keyword(s):

Nitric Oxide ◽

Antioxidant Enzymes ◽

Nitric Oxide Synthase ◽

Gastric Mucosa ◽

Hydroxyl Radical ◽

Oxide Synthase

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A Systematic DFT Study of Two Elementary Steps Involving Hydrogen Peroxide and the Hydroxyl Radical in the Fenton Reaction

10.26434/chemrxiv.6160142 ◽

2018 ◽

Author(s):

Danilo Carmona ◽

David Contreras ◽

Oscar A. Douglas-Gallardo ◽

Stefan Vogt-Geisse ◽

Pablo Jaque ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Hydroxyl Radical ◽

Ab Initio ◽

Fenton Reaction ◽

Basis Set ◽

Basis Sets ◽

Dft Methods ◽

Elementary Steps ◽

Oxygen Oxygen ◽

Complete Basis Set

The Fenton reaction plays a central role in many chemical and biological processes and has various applications as e.g. water remediation. The reaction consists of the iron-catalyzed homolytic cleavage of the oxygen-oxygen bond in the hydrogen peroxide molecule and the reduction of the hydroxyl radical. Here, we study these two elementary steps with high-level ab-initio calculations at the complete basis set limit and address the performance of different DFT methods following a specific classification based on the Jacob´s ladder in combination with various Pople's basis sets. Ab-initio calculations at the complete basis set limit are in agreement to experimental reference data and identified a significant contribution of the electron correlation energy to the bond dissociation energy (BDE) of the oxygen-oxygen bond in hydrogen peroxide and the electron affinity (EA) of the hydroxyl radical. The studied DFT methods were able to reproduce the ab-initio reference values, although no functional was particularly better for both reactions. The inclusion of HF exchange in the DFT functionals lead in most cases to larger deviations, which might be related to the poor description of the two reactions by the HF method. Considering the computational cost, DFT methods provide better BDE and EA values than HF and post--HF methods with an almost MP2 or CCSD level of accuracy. However, no systematic general prediction of the error based on the employed functional could be established and no systematic improvement with increasing the size in the Pople's basis set was found, although for BDE values certain systematic basis set dependence was observed. Moreover, the quality of the hydrogen peroxide, hydroxyl radical and hydroxyl anion structures obtained from these functionals was compared to experimental reference data. In general, bond lengths were well reproduced and the error in the angles were between one and two degrees with some systematic trend with the basis sets. From our results we conclude that DFT methods present a computationally less expensive alternative to describe the two elementary steps of the Fenton reaction. However, choice of approximated functionals and basis sets must be carefully done and the provided benchmark allows a systematic validation of the electronic structure method to be employed

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