I. V. Tikhonov

The kinetics and mechanism of reactions of aliphatic stable nitroxyl radicals with alkyl and peroxide radicals during styrene oxidation

A kinetic study (EPR, microvolumometry), quantum-chemical analysis (DFT B3LYP/6-31G*), and kinetic simulation of the antioxidant activity of aliphatic stable nitroxyl radicals during styrene oxidation was performed. The key reactions constituting the detailed mechanism of the process were analyzed. It was shown that the inhibiting action of nitroxyl radicals was caused by their reaction not only with alkyl radicals but also with substrate peroxy radicals, which resulted in the regeneration of nitroxyl radicals in chain-termination steps.

Stable nitroxyl radicals and hydroxylamines as inhibitors of methyl linoleate oxidation in micelles

The kinetics of methyl linoleate oxidation in micelles inhibited by nitroxyl radicals and hydroxylamines was studied. The regeneration of nitroxyl radicals in this process was found. The activity of the studied inhibitors increases with increasing their lipophilicity. This effect was explained by increasing the distribution coefficient of the antioxidants in a micelles–water system. The reaction of nitroxyl radicals with the hydroperoxide radical formed upon the oxidation of methyl linoleate in micelles is proposed to be the key reaction in nitroxyl radical regeneration.

Five-membered cyclic nitroxyl radicals as inhibitors of the oxidation of methyl linoleate in micelles

The kinetics of methyl linoleate oxidation in micelles inhibited by five-membered cyclic nitroxyl radicals and the corresponding hydroxylamines was studied. The partial regeneration of nitroxyl radicals in this process was found. The activity of the studied inhibitors increases with an increase in their lipophilicity.

Multiple chain termination by aromatic nitroxides in oxidation of styrene

The antioxidant activity of aromatic nitroxides in the oxidation of styrene was studied using a complex of kinetic methods in combination with quantum chemical calculations and kinetic modeling. During oxidation of styrene and its saturated analog, ethylbenzene, aromatic nitroxides terminate oxidation chains via the reaction with both alkyl and peroxyl radicals. The mechanism of the process was proposed, which explains multiple chain termination by the interaction of peroxyl and nitroxide radicals revealed in the investigation of styrene oxidation.

Quantum-chemical analysis of the disproportionation of nitroxyl and peroxyl radicals in oxidizing organic compounds

The enthalpy change of disproportionation reaction of nitroxyl and peroxyl radicals was calculated by the DFT B3LYP/cc-pVDZ method. The regeneration of the corresponding hydroxylamine during the oxidation of unsaturated compounds inhibited by nitroxyl radicals is shown to be associated with the disproportionation of the nitroxyl and peroxyl radicals.

Kinetics and Mechanism of Reactions of Aliphatic Stable Nitroxide Radicals in Chemical and Biological Chain Processes

© 2012 Pliss et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Kinetics and Mechanism of Reactions of Aliphatic Stable Nitroxide Radicals in Chemical and Biological Chain Processes

Superoxide radicals in the kinetics of nitroxide-inhibited oxidation of methyl linoleate in micelles

The kinetics of the oxidation of methyl linoleate in micelles inhibited by stable nitroxides under the conditions of initiation by superoxide radicals was studied. Multiple breakdown of the oxidation chains was observed in this process. The antioxidant activity of nitroxides increased when the reduction potential of the oxoammonium cation/nitroxide pair decreased and their lipophilicity increased.

Nitroxyl radicals as antioxidants against lipid peroxidation: An in vitro study

α-Methylacyl-CoA racemase (AMACR; P504S) catalyzes a key step in the degradation of branched-chain fatty acids and is important for the pharmacological activation of Ibuprofen and related drugs. Both the concentration and activity of AMACR are increased in prostate and other cancer cells, and the enzyme is a recognized drug target. However, all of the reported inhibitors are acyl-CoA esters (which do not comply with Lipinski guidelines) or non-specific protein modifying agents. Libraries of ~20,000 drug-like compounds were screened using a novel colorimetric assay; Incubation of R,S-2-3-(2,4-dinitrophenoxy)-2-methylpropanoyl-CoA with active AMACR resulted in the elimination of the strongly yellow 2,4-dinitrophenoxide and allows continuous measurement of activity in a microtitre plate format. Inhibitors were identified by a reduction in the rate of reaction in the presence of the library compound vs. the control. A number of novel reversible inhibitors were identified and their potency determined using dose-response curves. The results demonstrate the utility of the assay for the discovery and characterization of AMACR inhibitors as anti-cancer agents. This work was funded by Prostate Cancer UK (PG14-009), a Biochemical Society Summer Vacation Studentship Award, The Nuffield Foundation and MRC technology.

Effect of superoxide dismutase on the oxidation of methyl linoleate in micelles inhibited by nitroxyl radicals

The kinetics of oxidation of methyl linoleate in micelles inhibited by stable nitroxyl radicals in the presence of superoxide dismutase was studied. In the presence of superoxide dismutase, nitroxyl radicals decrease the rate of oxidation to a lower extent and the process is characterized by lower inhibition coefficients. The results obtained demonstrate an important role of hydroperoxide radical in the mechanism of nitroxyl radical regeneration during the oxidation of methyl linoleate in micelles.