Antioxidants adducts

Another example where antioxidant performance can be improved dramatically lies in the mechanochemlcally initiated addition of reactive antioxidants on rubbers (5.10) or unsaturated thermoplastics such as ABS (12). For example, using thiol antioxidants 2 and 3 as the reactive antioxidants, Kharasch-type addition of the thiol function to the polymer double bond takes place during melt processing to give bound antioxidant adduct (see Equation 1) the polymer becomes much more substantive under aggressive environments. 

Scheme 4 Antioxidant adduct formation in PVC during processing...

This method is potentially the most versatile, since it can be carried out in a variety of ways and adds relatively little to the cost of the final polymer. The nitroso-ene reaction in natural rubber already referred to is one example of such a modification. However, in order to avoid the necessity to gear the modification process to the vulcanisation reaction, we have concentrated in our own work on antioxidant adduct formation to the rubber double bonds either by vinyl grafting or by the Kharasch thiol addition reaction... 

The free radical addition of thiols to olefins provides TOtentially versatile method for antioxidant adduct formation in rubbers. This is shown for nitrile-butadiene rubber in Scheme 1, but it is applicable in principle to any rubber which has a reactive double bond. Three main methods have been used to carry out the reaction. 

Hydrogen haHde addition to vinyl chloride in general yields the 1,1-adduct (50—52). The reactions of HCl and hydrogen iodide [10034-85-2], HI, with vinyl chloride proceed by an ionic mechanism, while the addition of hydrogen bromide [10035-10-6], HBr, involves a chain reaction in which a bromine atom [10097-32-2] is the chain carrier (52). In the absence of a transition-metal catalyst or antioxidants, HBr forms the 1,2-adduct with vinyl chloride (52). HF reacts with vinyl chloride in the presence of stannic chloride [7646-78-8], SnCl, to form 1,1-difluoroethane [75-37-6] (53). 

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). 

Adducts other than N bases are thiourea,909 phosphine,880 and N,0-donors (hydroxyquinoline derivatives).910 In the last case NiONS2 complexes were formed. Generally, complexes of dithiophosphates are used as antiwear and antioxidant additives. 

Zinc dithiocarbamates have been used for many years as antioxidants/antiabrasives in motor oils and as vulcanization accelerators in rubber. The crystal structure of bis[A, A-di- -propyldithio-carbamato]zinc shows identical coordination of the two zinc atoms by five sulfur donors in a trigonal-bipyramidal environment with a zinc-zinc distance of 3.786 A.5 5 The electrochemistry of a range of dialkylthiocarbamate zinc complexes was studied at platinum and mercury electrodes. An exchange reaction was observed with mercury of the electrode.556 Different structural types have been identified by variation of the nitrogen donor in the pyridine and N,N,N, N -tetra-methylenediamine adducts of bis[7V,7V-di- .vo-propyldithiocarbamato]zinc. The pyridine shows a 1 1 complex and the TMEDA gives an unusual bridging coordination mode.557 The anionic complexes of zinc tris( V, V-dialkyldithiocarbamates) can be synthesized and have been spectroscopically characterized.558... 

The work by Hill et al. also noted differences for ASTA compared with the other carotenoids studied. Its radical cation was not formed initially from CC1302 but was formed solely through the proposed addition radical. Unfortunately, LYC could not be studied due to its insolubility in TX 100 micelles. However, since LYC appears, from its quenching of 02 and its protection against N02 to be the most efficient natural carotenoid antioxidant, we repeated this work using 4% TX 405 TX 100 (4 1) mixed micelles for both 0-CAR and LYC (unpublished) and have observed LYC behaving in a different manner to the other carotenoids as there appears to be no conversion of the adduct to the radical cation. 

In case of scavenging of lipid-derived peroxyl radicals (LOO"), the radical adduct formed [LOO-CaiT is less reactive than the LOO, so carotenoids act as chain-breaking antioxidants in lipid peroxidation (Equation 15.6) ... 

The scavenging ability toward O2 can also be measured by using electron spin resonance (ESR) spectrometry. The 02 anion is trapped with 5,5-dimethyl-1-pyrroline TV-oxidc (DMPO), and the resultant DMPO-OH adduct is detected by ESR using manganese oxide as internal standard. Noda and others (1997) used this technique to evaluate antioxidant activities of pomegranate fruit extract and its anthocyanidins (delphinidin, cyanidin, and pelargonidin). 

At the same time the interaction of superoxide with MPO may affect a total superoxide production by phagocytes. Thus, the superoxide adduct of MPO (Compound III) is probably quantitatively formed in PMA-stimulated human neutrophils [223]. Edwards and Swan [224] proposed that superoxide production regulate the respiratory burst of stimulated human neutrophils. It has also been suggested that the interaction of superoxide with HRP, MPO, and LPO resulted in the formation of Compound III by a two-step reaction [225]. Superoxide is able to react relatively rapidly with peroxidases and their catalytic intermediates. For example, the rate constant for reaction of superoxide with Fe(III)MPO is equal to 1.1-2.1 x 1061 mol 1 s 1 [226], and the rate constants for the reactions of Oi and HOO with HRP Compound I are equal to 1.6 x 106 and 2.2 x 1081 mol-1 s-1, respectively [227]. Thus, peroxidases may change their functions, from acting as prooxidant enzymes and the catalysts of free radical processes, and acquire antioxidant catalase properties as shown for HRP [228] and MPO [229]. In this case catalase activity depends on the two-electron oxidation of hydrogen peroxide by Compound I. 

Witte P, Beuerle F, Hartnagel U, Lebovitz R, Savouchkina A, Sali S, Guldi D, Chionakis N, Hirsch A (2007) Water-solubility, antioxidant activity and cytochrome C binding of four families of exohedral adducts of C60 and C7Q. Org. Biomol. Chem. 5 3599-3613. 

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. 

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