Radical mechanisms thiols, oxidation

Gilbert and coworkers18 were able to detect ESR spectra of sulfinyl radicals together with other sulfur-centered radicals during the oxidation of disulfides and thiols with a titanium(III)-peroxide couple reaction mechanisms involving sulfenic acids as intermediates have been discussed. 

Organic peroxides such as cumene hydroperoxide and t-butyl hydroperoxide have extensively been used as experimental agents. They provoke lipid peroxidation in hepatocytes, probably by the generation of alkoxyl and peroxyl radical intermediates after reaction with cytochrome P450. Other cytotoxic mechanisms are probably involved including protein thiol and non-protein thiol oxidation and deranged calcium homeostasis (Jewell et al., 1986). In fact, the addition of cumene hydroperoxide to isolated bUe duct cells, devoid of cytochrome P450 activity, still results in cell death but lipid peroxidation is not detectable (Parola et al., 1990). 

Phenol-induced oxidative stress mediated by thiol oxidation, antioxidant depletion, and enhanced free radical production plays a key role in the deleterious activities of certain phenols. In this mode of DNA damage, the phenol does not interact with DNA directly and the observed genotoxicity is caused by an indirect mechanism of action induced by ROS. A direct mode of phenol-induced genotoxicity involves covalent DNA adduction derived from electrophilic species of phenols produced by metabolic activation. Oxidative metabolism of phenols can generate quinone intermediates that react covalently with N-1,N of dG to form benzetheno-type adducts. Our laboratory has also recently shown that phenoxyl radicals can participate in direct radical addition reactions with C-8 of dG to form oxygen (O)-adducts. Because the metabolism of phenols can also generate C-adducts at C-8 of dG, a case can be made that phenoxyl radicals display ambident (O vs. C) electrophilicity in DNA adduction. 

Peroxides generated on peptides using l02 can also inactivate enzymes by a non-radical mechanism, possibly involving the oxidation of cysteinyl thiol resi-... 

Meanwhile, there are many substrates of FMO already known, including tertiary and secondary amines, hydroxyamines, thiols, sulfides, thiocar-bamides, and thioamides (for a review, see Ziegler, 1991). Compounds accepted by this mono-oxygenase have one chemical properly in common All are soft nucleophiles readily oxidized by per-adds. Apparently, the nudeophilic centers are oxidized by an ionic r er than a radical mechanism in an active site requiring more than one point of contact (Ziegler, 1991). 

The oxidation of thiols follows a completely different course as compared with the oxidation of alcohols, because the capacity of the sulfur atom to form hypervalent compounds allows it to become the site of oxidation. Thiols are readily oxidised to disulfides by mild oxidants such as atmospheric oxygen, halogens or iron(III) salts (Scheme 6). This type of reaction is unique to thiols and is not undergone by alcohols, it is a consequence of the lower bond strength of the S-H as compared with the O-H bond, so that thiols are oxidised at the weaker S-H bonds, whereas alcohols are preferentially oxidised at the weaker C-H bonds (Scheme 7). The mechanism of oxidation of thiols may be either radical or polar or both (Scheme 6). The polar mechanism probably involves transient sulfenic acid intermediates like (7) and (8). In contrast, thiols react with more powerful oxidants, like potassium permanganate, concentrated nitric acid or hydrogen peroxide, to yield the corresponding sulfonic acids (10). This oxidation probably proceeds via the relatively unstable sulfenic (7) and sulfinic acids (9), which are too susceptible to further oxidation to be isolated (Scheme 8). 

The biochemical mechanism of pulmonary injury is due to the formation of reactive free-radical intermediates from oxidization of thiol-containing compounds and unsaturated fatty acids. The primary site of injury is the lung, and the injury is characterized by pulmonary congestion, edema, and hemorrhage. 

Jourd heuil D., Jourd heuil F. L., Feelisch M., Oxidation and nitrosation of thiols at low micromolar exposure to nitric oxide. Evidence for a free radical mechanism, J. Biol. Chem., 2003, 278,15720-15726. 

Product stability and performance can be affected by exposure to several oxidative sources, including oxygen, free radicals, UV radiation, oxidative enzymes, catabolic oxidation, and chemical oxidation. Many antioxidants are also good UV absorbers due to their conjugated chemical structure. Typical antioxidants found in cosmetic products are flavonoids, polyphenols, carotenoids, thiols, tocopherol (vitamin E) and ascorbic acid (vitamin C) [71,72], According to Black [73], a combination of antioxidants from different classes is more effective than a single antioxidant due to an antioxidant cascade mechanism. 

Previous study [18] on oxidation of thiols by transition metal oxide(s) in the presence of olefins resulted in the formation of corresponding sulphides indicating a free radical addition reaction in which metal oxide acts as an initiator for the production of thiyl radicals(RS-). The disulphide is formed by the dimerization of thiyl radieals (RS )- Based on this, a mechanism for thiol oxidation by manganese nodule (Only oxides of Mn, Fe, Co and Cu in manganese nodule are responsible for oxidation of thiols) is delineated as follows ... 

The mechanism of oxidative ring closure of compounds of the 1,3-butadiene-1-thiol type with halogens to give thiophen derivatives has been studied by Chapman.A polar mechanism has been assumed, although a free radical mechanism is not completely ruled out and, indeed, is proposed for the cycliza-tion under other conditions. Thus, photolysis of the disulfide 124 in boiling xylene gives the thiophen 125 in 40% yield the proposed mechanism is depicted in Scheme 59. Such a mechanism involves efficient cyclization toward the (Cy5) compound in a Cy5/Cy4 case and the conversion of the (Cy 5) radical into a thiophene. 

The reactive species that iaitiate free-radical oxidatioa are preseat ia trace amouats. Exteasive studies (11) of the autoxidatioa mechanism have clearly estabUshed that the most reactive materials are thiols and disulfides, heterocycHc nitrogen compounds, diolefins, furans, and certain aromatic-olefin compounds. Because free-radical formation is accelerated by metal ions of copper, cobalt, and even iron (12), the presence of metals further compHcates the control of oxidation. It is difficult to avoid some metals, particularly iron, ia fuel systems. 

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