Phenolic antioxidants adducts

Ab initio molecular mechanics calculations have been used to examine the electronic states of selenoxanthene 9 and selenoxanthone 10. These results were used to explain differences in the formation of bromine adducts of these compounds (see Section 7.11.6.1.2) <1998JOC8373>. Bond dissociation enthalpies and adiabatic ionization potentials of phenolic antioxidants containing selenium and tellurium have been carried out using DFT models in an attempt to design novel vitamin E analogues such as 11 <20060BC846>. 

Phenols are important antioxidants, with vitamin E being the most important endogenous phenolic membrane-bound antioxidant. Membrane levels of vitamin E are maintained through recycling of the vitamin E radical with ascorbate and thiol reductants. Vitamin E is a mixture of four lipid-soluble tocopherols, a-tocopherol being the most efiective radical quencher. The reaction of a-tocopherol with alkyl and alkylperoxyl radicals of methyl linoleate was recently reported. These are facile reactions that result in mixed dimer adducts (Yamauchi etal., 1993). 

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. 

There is a growing interest in naturally occurring phenolic compounds that display biological antioxidant properties such as -hydroxycinnamic acid, ferulic zcid, caffeic acid/ and curcumin which are ubiquitous in plant food. It has been demonstrated that the interaction of the oxidizing OH adduct of DNA, poly-A and poly-G with hydrox-ycinnamic acid derivatives proceed via electron transfer. Cinnamic acid derivatives have been shown to be able to scavenge superoxide, peroxyl, and hydroxyl radicals. 

The formation of heterocychc amines of the IQ type is effectively inhibited by antioxidants. The presence of phenohc compounds such as flavanones and flavan-3-ols significantly inhibits their formation. The mechanism of the inhibitory effect is partly based on the ehmination of Strecker aldehydes, precursors of IQ mutagens, by condensation with phenols. For example, phenylacetaldehyde, a decarboxylation product of phenylalanine and a precursor of PhIP, produces two adducts, ( )-8-(phenylethenyl)naringenin and ( )-6-(phenylethenyl)naringenin withnaringenin (Figure 12.2). 

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