Oxidation radical-mediated

Walkup, L.K. Kogoma, T. (1989). E. coli proteins inducible by oxidative stress mediated by the superoxide radical. J. Bacteriol. 171, 1476-1484. 

Radical-mediated silyldesulfonylation of various vinyl and (a-fluoro)vinyl sulfones 21 with (TMSlsSiH (Reaction 25) provide access to vinyl and (a-fluoro)vinyl silanes 22. These reactions presumably occur via a radical addition of (TMSlsSi radical followed by /)-scission with the ejection of PhS02 radical. Hydrogen abstraction from (TMSlsSiH by PhS02 radical completes the cycle of these chain reactions. Such silyldesulfonylation provides a flexible alternative to the hydrosilylation of alkynes with (TMSlsSiH (see below). On oxidative treatment with hydrogen peroxide in basic aqueous solution, compound 22 undergoes Pd-catalyzed cross-couplings with aryl halides. 

KERRY N and ABBEY M (1998) The isoflavone genistein inhibits copper and peroxyl radical mediated low density lipoprotein oxidation in vitro. Atherosclerosis. 140 (2) 341-7. 

Merry, P., Grootveld, M., Lunec, J. and Blake, D.R (1991). Oxidative damage to lipids within the inflamed human joint provides evidence of radical-mediated hypoxic-reperfusion injury. Am. J. Clin. Nutr. 53, 362S-369S. 

Sato, K., Niki, E. and Shimasaki, H. (1990). Free radical mediated chain oxidation of LDL and its synergistic inhibition by vitamin E and vitamin C. Arch. Biochem. Biophys. 279, 402-405. 

A sustained inhibition of the Na/K pump following a period of oxidant stress would be expected to raise intracellular sodium and favour calcium influx via the Na/Ca exchanger. Ischaemia and reperflision-induced oxidant stress, therefore, may result in a loss of Na/K pump activity, an eflFect that may involve free-radical-mediated changes in cellular thiol status. 

Probucol, another di-r-butyl phenol, is an anti-atherosclerotic agent that can suppress the oxidation of low-density lipoprotein (LDL) in addition to lowering cholesterol levels. The antioxidant activity of probucol was measured, using EPR, with oxidation of methyl linoleate that was encapsulated in liposomal membranes or dissolved in hexane. Probucol suppressed ffee-radical-mediated oxidation. Its antioxidant activity was 17-fold less than that of tocopherol. This difference was less in liposomes than in hexane solution. Probucol suppressed the oxidation of LDL as efficiently as tocopherol. This work implies that physical factors as well as chemical reactivity are important in determining overall lipid peroxidation inhibition activity (Gotoh et al., 1992). 

Radical attack yields nucleobase radical adducts that must undergo either oxidation or rednction to yield a stable final prodnct. The cellular oxidant in these reactions may be molecnlar oxygen or high-valent transition metal ions (e.g., Fe ), while the reduc-tant may be either thiols, snperoxide radical, or low-valent transition metal ions (e.g., Fe ). In many cases, the base remains largely intact and the seqnence of chemical events can be readily inferred. In some other cases, more extensive base decomposition occurs. Here, we will consider a set of representative examples that provide a framework for understanding virtnally all radical-mediated base damage reactions. 

Jahangir T et al (2005) Alleviation of free radical mediated oxidative and genotoxic effects of cadmium by farnesol in Swiss albino mice. Redox Rep 10(6) 303-310... 

Much attention has been paid during the two last decades to the elucidation of oxidation reactions mediated by oxygen ( OH radical, H202, 102, 03,... 

Deoxycytidine (dCyd) (14 in Scheme 2) is also an excellent target for one-electron oxidation reactions mediated by triplet excited menadione. On the basis of extensive identification of dCyd photooxidation products, it was concluded that this nucleoside decomposes by competitive hydration and deprotonation reactions of cytosine radical cations with yields of 52% and 40%, respectively [53]. It was also found, on the basis of 180 labeling experiments, that hydration of cytosine radical cations (15) predominantly occurs... 

Other degradation products of the cytosine moiety were isolated and characterized. These include 5-hydroxy-2 -deoxycytidine (5-OHdCyd) (22) and 5-hydroxy-2 -deoxyuridine (5-OHdUrd) (23) that are produced from dehydration reactions of 5,6-dihydroxy-5,6-dihydro-2 -deoxycytidine (20) and 5,6-dihydroxy-5,6-dihydro-2 -deoxyuridine (21), respectively. MQ-photosen-sitized oxidation of dCyd also results in the formation of six minor nucleoside photoproducts, which include the two trans diastereomers of AT-(2-de-oxy-/j-D-eryf/iro-pentofuranosyl)-l-carbamoyl-4 5-dihydroxy-imidazolidin-2-one, h/1-(2-deoxy-J8-D-crythro-pentofuranosyl)-N4-ureidocarboxylic acid and the a and [5 anomers of N-(2-deoxy-D-eryfhro-pentosyl)-biuret [32, 53]. In contrast, formation of the latter compounds predominates in OH radical-mediated oxidation of the pyrimidine ring of dCyd, which involves preferential addition of OH radicals at C-5 followed by intramolecular cyclization of 6-hydroperoxy-5-hydroxy-5,6-dihydro-2 -deoxycytidine and subsequent generation of the 4,6-endoperoxides [53]. 

Interestingly, the nucleophilic addition of water in the sequence of events giving rise to 41 represents a relevant model system for investigating the mechanism of the generation of DNA-protein cross-links under radical-mediated oxidative conditions [80, 81]. Thus, it was shown that lysine tethered to dGuo via the 5 -hydroxyl group is able to participate in an intramolecular cyclization reaction with the purine base at C-8, subsequent to one electron oxidation [81]. 

One-electron oxidation of the adenine moiety of DNA and 2 -deoxyadenos-ine (dAdo) (45) gives rise to related purine radical cations 46 that may undergo either hydration to generate 8-hydroxy-7,8-dihydroadenyl radicals (47) or deprotonation to give rise to the 6-aminyl radicals 50. The formation of 8-oxo-7,8-dihydro-2 -deoxyadenosine (8-oxodAdo) (48) and 4,6-diamino-5-formamidopyrimidine (FapyAde) (49) is likely explained in terms of oxidation and reduction of 8-hydroxy-7,8-dihydroadenyl precursor radicals 47, respectively [90]. Another modified nucleoside that was found to be generated upon type I mediated one-electron oxidation of 45 by photoexcited riboflavin and menadione is 2 -deoxyinosine (51) [29]. The latter nucleoside is likely to arise from deamination of 6-aminyl radicals (50). Overall, the yield of formation of 8-oxodAdo 48 and FapyAde 49 upon one-electron oxidation of DNA is about 10-fold-lower than that of 8-oxodGuo 44 and FapyGua 43, similar to OH radical mediated reactions [91]. 

Yamauchi, R. and K. Kato (1998). Products formed by peroxyl radical-mediated oxidation of canthaxanthin in benzene and in methyl linoleate. J. Agric. Food Chem. 46(12) 5066-5071. 

Lim, B. P., A. Nagao et al. (1992). Anti-oxidant activity of xanthophylls on peroxyl radical-mediated phospholipid peroxidation. Biochim. Biophys. Acta 1126 178-184. 

Reported redox potentials of laccases are lower than those of non-phenolic compounds, and therefore these enzymes cannot oxidize such substances [7]. However, it has been shown that in the presence of small molecules capable to act as electron transfer mediators, laccases are also able to oxidize non-phenolic structures [68, 69]. As part of their metabolism, WRF can produce several metabolites that play this role of laccase mediators. They include compounds such as /V-hvdi oxvacetan i I ide (NHA), /V-(4-cyanophenyl)acetohydroxamic acid (NCPA), 3-hydroxyanthranilate, syringaldehyde, 2,2 -azino-bis(3-ethylben-zothiazoline-6-sulfonic acid) (ABTS), 2,6-dimethoxyphenol (DMP), violuric acid, 1-hydroxybenzotriazole (HBT), 2,2,6,6-tetramethylpipperidin-iV-oxide radical and acetovanillone, and by expanding the range of compounds that can be oxidized, their presence enhances the degradation of pollutants [3]. 

Peroxyl radicals are the species that propagate autoxidation of the unsaturated fatty acid residues of phospholipids (50). In addition, peroxyl radicals are intermediates in the metabolism of certain drugs such as phenylbutazone (51). Epoxidation of BP-7,8-dihydrodiol has been detected during lipid peroxidation induced in rat liver microsomes by ascorbate or NADPH and during the peroxidatic oxidation of phenylbutazone (52,53). These findings suggest that peroxyl radical-mediated epoxidation of BP-7,8-dihydrodiol is general and may serve as the prototype for similar epoxidations of other olefins in a variety of biochemical systems. In addition, peroxyl radical-dependent epoxidation of BP-7,8-dihydrodiol exhibits the same stereochemistry as the arachidonic acid-stimulated epoxidation by ram seminal vesicle microsomes. This not only provides additional... 

Microsomal Free Radical-Mediated Oxidative Processes... 

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