Phenoxyl radicals addition reactions

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. 

Simple radical-radical addition reactions would not be expected to show any pH dependence. The pH effects seen here (Figs. 3-6) are likely due to the ratios of ONOO" and ONOOH (pKa, 6.8) and to the greater ease with which phenoxylate anion (pK 10) undergoes one-electron oxidation reactions. Overall, the nitrated and hydroxylated products from ONOO"/ phenol reactions can be explained using Scheme 4, whereby phenol undergoes a one-electron oxidation by either radical end of ONOO" to yield phenoxyl radical, followed by concerted addition of the remaining radical end of ONOO". Increased nitrosation when both ONOO" and nitric oxide are added simultaneously can be explained in terms of one-electron oxidation of nitric oxide by ONOO" to yield NO, which directly attacks phenol. Oxidation of nitric oxide to NO is also consistent with nitric oxide... 

Among the abundance of tested classes of substances, PCA is the only additive reliably protecting PSF from oxidation in concentrations below 0.3 wt.%. As expected, by analogy with polycarbonate and other heterochain polymers processed at temperatures about 300°C, classical primary antioxidants (hindered phenols and aromatic amines) are at most neutral (amines catastrophically color PSF), which proved existence of the effective inhibition temperature limit (120 - 125°C) [11, p. 218]. It is stipulated by activity of phenoxyl radicals in reactions with hydroperoxides. Commonly, all so-called non-chain inhibitors intensify... 

The estimation based on the equations of the parabolic model indicates that a reaction of the type (ArO + H02 —> ArOH + 02) involving phenoxyl radicals also requires no activation energy (in this case, AH> A emin = 57kJ mol-1). However, the addition of the peroxyl radical to the aromatic ring of the phenoxyl radical occurs very rapidly. Hence, the rate constant for this reaction is determined by diffusion processes. The data on the Ee0 values are also consistent with this. For the ArO + HOOR reactions with the O H O reaction center and for Am + HOOR reactions with the N H O reaction center, these values are 45.3 and 39.8 kJ mol-1, respectively [23]. At the same time, the calculation of the preexponential factor in terms of the parabolic model indicates that the rate constant k 7 for the reaction of ROOH with the participation of the aminyl radical is several times higher than that for the reaction involving the phenoxyl radical, where the enthalpies of these reactions... 

Sulfur compounds in combination with peroxyl radical acceptors are often used for the efficient break of hydroperoxide [14]. The mechanism of action of these inhibitory mixtures can, however, be more complex, as demonstrated with reference to a pair of 2,6-diphenylphenol and distearyl dithiopropionate [15]. The combined addition of these compounds with concentrations of 0.05% and 0.3%, respectively, results in an extended inhibitory period during the oxidation of PP (up to 3000 h at 413 K). Sulfide (for instance, (3,(3 -diphenylethyl sulfide) or its products not only break down ROOH, but also reduce the phenoxyl radical. Sulfoxide formed in the reaction of the sulfide with ROOH can react with ArO. Thus, the ability of sulfides and their products to reduce phenoxyl radicals can contribute to their synergistic effect. 

FIGURE 19.2 The correlation of rate constants of various free radical reactions with molecular mobility of nitroxyl radical in the polymer matrix of different polymers with addition of plastificator I in IPP, II in preliminary oxidized IPP, III in PE, and IV in PS. Line 1 for the reaction of 2,6-bis(l,l-dimethy-lethyl)phenoxyl radical with hydroperoxide groups at T — 295 K line 2 for the reaction of 2,2,6, 6-tetramethyl-4-bcnzoyloxypiperidinc-/V-oxyl with 1-naphthol at T = 333 K line 3 for the reaction of 2,2,6,6-tetramethyl-4-benzoyloxypiperidine-iV-oxyl with 2,6-bis(l,l-dimethylethyl)phenol at T = 333 K line 4 for the same reaction at 7 — 303 K line 5 for the same reaction at T = 313 K and line 6 for the same reaction at T — 323 K [18]. 

Reactions described earlier were not limited by rotational diffusion of reactants. It is evident that such bimolecular reactions can occur that are limited not by translational diffusion but by the rate of reactant orientation before forming the TS. We discussed the reactions of sterically hindered phenoxyl recombination in viscous liquids (see Chapter 15). We studied the reaction of the type radical + molecule, which are not limited by translational diffusion in a solution but are limited by the rate of reactant orientation in the polymer matrix [28]. This is the reaction of stable nitroxyl radical addition to the double bond of methylenequinone. 

The oxidation of PIB occurs mainly via intramolecular addition of dioxygen to double bonds of polymer. The reaction of peroxyl radical addition to the phenoxyl radical leads to the formation of quinolide peroxide (see Chapter 15). This peroxide is unstable, and its decomposition provokes the degradation of PIB. Another reaction predominates in case of aromatic diamine. 

The O atom could venture through a displacement and possibly an addition [60] reaction to form a phenoxyl radical and phenol according to the steps... 

Phenoxyl radicals are oxidizing radicals (for a compilation of redox potentials see Wardman 1989). Thus, in their reactions with 02 (E7 = -0.3 V) there is ample driving force for a reduction by ET [cf. reaction (16)], and this has been thought for a long time to be the only (Hunter et al. 1989) or at least a major process, depending on the reduction potential of the (substituted) phenoxyl radical (Jonsson et al. 1993). Yet in the tyrosine system, despite of the high reduction potential of tyrosine phenoxyl radical (E7 = 0.64 V), the by far dominating process is addition, and the intermediate adduct is locked in by a Mannich reaction [reactions (14) and (15) Jin et al. 1993],... 

Tryptophan and its derivatives such as the Hoechst compounds (Adhikary et al. 2000) have reduction potentials below that of G (tryptophan E7 = 1.0 V Jovanovic and Simic 1985) and thus are capable of repairing some of the DNA damage (for a review on indol free-radical chemistry see Candeias 1998 for the thermochemistry of N-centered radicals see Armstrong 1998). In these reactions, radical cations and N-centered radicals are formed. Similar to phenoxyl radicals, these radical react with 02- mainly by addition despite the large difference in the redox potential which would allow an ET as well (Fang et al. 1998). 

Hug GL, Bonifacic M, Asmus K-D, Armstrong DA (2000a) Fast decarboxylation of aliphatic amino adds induced by 4-carboxybenzophenone triplets in aqueous solutions. A nanosecond laser flash photolysis study. J Phys Chem B 104 6674-6682 Hug GL, Carmichael I, Fessenden RW (2000b) Direct EPR observation of the aminomethyl radical during the radiolysis of glycine. J Chem Soc Perkin Trans 2 907-908 Hunter EPL, DesrosiersMF, Simic MG (1989) The effect of oxygen, antioxidants and superoxide radical on tyrosine phenoxyl radical dimerization. Free Rad Biol Med 6 581-585 Ito O (1992) Flash photolysis study for reversible addition reactions of thiyl radicals with olefins and acetylenes. Trends Phys Chem 3 245-266... 

Jin F, Leitich J, von Sonntag C (1993) The superoxide radical reacts with tyrosine-derived phenoxyl radicals by addition rather than by electron transfer. J Chem Soc Perkin Trans 2 1583-1588 Jonsson M, Lind J, Reitberger T, Eriksen TE, Merenyi G (1993) Free radical combination reactions involving phenoxyl radicals. J Phys Chem 97 8229-8233 Jovanovic SV, Simic MG (1985) Repair of tryptophan radicals by antioxidants. J Free Rad Biol Med 1 125-129... 

The ascorbate radical is one of the radicals that do not react readily with 02, but it reacts with 02 ". The product of this reaction is not yet known. There are other radicals that have similar properties such as phenoxyl-type radicals. A prominent member of this group is the vitamin E radical. In the phenoxyl radical series, addition as well as ET have been discussed (Jonsson et al. 1993 d Alessandro et al. 2000). The reaction of the tyrosyl radical with 02 is an example showing that addition is the main route despite of its relatively high redox potential [reactions (97)—(99) only one pathway is shown Jin et al. 1993],... 

Deeble DJ, von Sonntag C (1992) Decarboxylation of 3,4-dihydroxymandelic acid induced by the superoxide radical anion a chain reaction. Int J Radiat Biol 62 105 Deeble DJ, Parsons BJ, Phillips GO (1987) Evidence for the addition of the superoxide anion to the anti- oxidant -propyl gallate in aqueous solution. Free Rad Res Commun 2 351-358 Deeble DJ, Parsons BJ, Phillips GO, Schuchmann H-P, von Sonntag C (1988) Superoxide radical reactions in aqueous solutions of pyrogallol and n-propyl gallate the involvement of phenoxyl radicals. A pulse radiolysis study. Int J Radiat Biol 54 179-193 Denisov ET, Denisova TG (1993) The polar effect in the reaction of alkoxy and peroxy radicals with alcohols. Kinet Catal 34 738-744... 

It is well known that benzophenone generates a biradical through n-ir electronic transition under irradiation ( 340 nm). Irradiation of a mixture of 1,4-benzoquinone (34) and aromatic aldehydes in the presence of benzophenone generates 2-aroyl-l,4-dihydroxybenzene (35) [47-49]. This reaction comprises of the abstraction of a formyl hydrogen atom of an aromatic aldehyde by the oxygen-centered radical of the benzophenone biradical to form an aroyl radical and a 1,1-diphenylhydroxymethyl radical, and addition of the nucleophilic aroyl radical to 1,4-benzoquinone (34) to form a phenoxyl radical derivative, which finally abstracts a hydrogen atom from an aromatic... 

The spectral nature for the transients formed in the OH reaction with -hydroxybenzaldehyde (Fig. 8) was found to be different from those recorded with its ortho- and meta-isomcrs. In addition to a single peak around 370-410 nm observed with the latter, a more intense peak at 325 nm by four folds was seen. Furthermore, this peak decayed faster with a first-order rate constant k = 5.5 x 10 s"h This decay was found to be acid-catalyzed. In the reaction of OH radical with hydroxybenzaldehydes, the time resolved spectral changes are interpreted in terms of the formation of phenoxyl radical via intermediate radical cation in the case of ortho- and /rm-isomers whereas phenoxyl radical formation by dehydration seems to be the predominant reaction pathway for the w/Jt/r-isomer. 

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