Hydrogen activation free-radical mechanism

Inhibition and stimulation of LOX activity occurs as a rule by a free radical mechanism. Riendeau et al. [8] showed that hydroperoxide activation of 5-LOX is product-specific and can be stimulated by 5-HPETE and hydrogen peroxide. NADPH, FAD, Fe2+ ions, and Fe3+(EDTA) complex markedly increased the formation of oxidized products while NADH and 5-HETE were inhibitory. Jones et al. [9] also demonstrated that another hydroperoxide 13(5)-hydroperoxy-9,ll( , Z)-octadecadienoic acid (13-HPOD) (formed by the oxidation of linoleic acid by soybean LOX) activated the inactive ferrous form of the enzyme. These authors suggested that 13-HPOD attached to LOX and affected its activation through the formation of a protein radical. Werz et al. [10] showed that reactive oxygen species produced by xanthine oxidase, granulocytes, or mitochondria activated 5-LOX in the Epstein Barr virus-transformed B-lymphocytes. 

These radical species, along with others produced from their subsequent reactions, can react with biomolecules, such as proteins and DNA. The most damaging such reaction is lipid peroxidation, a process that involves the attack of chemically active species on unsaturated lipid molecules, followed by oxidation of the lipids through a free radical mechanism. It occurs in the liver and is a main mode of action of some hepatotoxicants, which can result in major cellular damage. The mechanism of lipid peroxidation may involve abstraction of the methylene hydrogens attached to doubly bonded carbon atoms in lipid molecules ... 

It was found that the action of OH radicals on nitrobenzene or benzoic acid produced all the three isomeric phenolic compounds. OH radicals produced, for example, by reaction (1) can be used to generate other free radicals or atoms from inorganic or organic compounds. These reactions have been studied more recently by Kolthoff and Medalia (13), Merz and Waters (46), Stein and Weiss (45), and others. Reaction (1) also proved useful in the study of the so-called active oxalic acid (47). The free radical mechanism of hydrogen peroxide has been discussed also in connection with the mechanism of the action of the enzymes catalase and peroxydase, the prosthetic groups of which are iron porphyrin complexes which presumably also undergo oxido-reduction processes in the course of their catalytic activity (48). 

Reduction of [IrCls] by a variety of agents has been cited. The reduction of [IrXs] " (Cl, Br) by 2-thiouracil and 2-thiopyrimidine follows second-order rate laws, first-order with respect to both the concentration of the oxidant and the reductant. A pH-rate profile as well as activation parameters have been presented, and a free radical mechanism proposed." Reduction in aqueous alcoholic solution by aquated electrons, hydrogen and alkyl radicals was investigated by pulse radiolysis, and found to result in the production of [IrClg] " A kinetic examination of reaction (123) in aqueous solution shows that this outer-sphere electron transfer reaction proceeds by parallel paths first and second order in substrate (SCN ). The kinetics of the oxidation of hydrazine by [Ir(Cl)4(H20)2], [Ir(Cl)5(H20)], [IrClef , as well as [IrBrsf , in aqueous acidic perchlorate solution have been investigated." ... 

Preliminary results of the reaction between vanadium(iii)-tetrasulpho-phthalocyanine complex with oxygen have been reported these data were compared with those obtained for the corresponding reaction of the hexa-aquo complex ion. The oxidation of methyl ethyl ketone by oxygen in the presence of Mn"-phenanthroline complexes has been studied Mn " complexes were detected as intermediates in the reaction and the enolic form of the ketone hydroperoxide decomposed in a free-radical mechanism. In the oxidation of 1,3,5-trimethylcyclohexane, transition-metal [Cu", Co", Ni", and Fe"] laurates act as catalysts and whereas in the absence of these complexes there is pronounced hydroperoxide formation, this falls to a low stationary concentration in the presence of these species, the assumption being made that a metal-hydroperoxide complex is the initiator in the radical reaction. In the case of nickel, the presence of such hydroperoxides is considered to stabilise the Ni"02 complex. Ruthenium(i) chloride complexes in dimethylacetamide are active hydrogenation catalysts for olefinic substrates but in the presence of oxygen, the metal ion is oxidised to ruthenium(m), the reaction proceeding stoicheiometrically. Rhodium(i) carbonyl halides have also been shown to catalyse the oxidation of carbon monoxide to carbon dioxide under acidic conditions ... 

Nitric oxide is a low-activity free radical and can be used as a counter of radicals in gas and liquid phases. The reactions of alkyl radicals with NO lead to the formation of nitroso compounds, which are spin traps. Thus, the initiation of free-radical reactions in solid polymers in the presence of nitric oxide provides further information on their mechanism. It is well established that at room temperature NO is not able to remove allylic and tertiary hydrogen atoms and add to isolated double bonds [24-26]. There are discrepant opinions on the capability of NO to react with low molecular weight (low molar mass) dienes and polyenes. Some authors believe that NO is able to add to dienes and polyenes, for example, to substituted o-quinonedimethane, phorone and P-carotene, with the formation of free radicals [27-29]. Another way of looking at these reactions lies in the fact that they can be initiated by NO2 impurities [25, 26]. 

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