Reactions with Peroxyl Radicals

In fact, 5-hydroxymethyluracil is a major oxidative DNA lesion, and is excreted into the urine in rather large amounts (Bianchini et al. 1996). 

The same reaction has been carried out with dGuo in the context of a study of mutagenic effects of peroxyl radicals on DNA (Valentine et al. 1998). Some products have been recognized by HPLC but were not identified. Gua is not released, and there was no evidence that 8-oxo-G is among the products. 

The thermolysis of dioxetanes in the presence of 02 also yields peroxyl radicals (alkylperoxyl and acetylperoxyl), and these generate upon their reaction with dGuo mainly Z and 4-HO-8-oxo-G with only small amounts of 8-oxo-G 

Mechanistically, it is difficult to see how some of these products that are well-known from OH-induced reaction maybe formed upon peroxyl-radical attack, for example, the glycols, and the question must be raised, whether these may arise from the thermal decomposition of hydroperoxides formed in preceding reactions such as reaction (223). 

This type of damage amplification reaction is also observed in polynucleotides and in DNA (Chaps 11.2 and 12.5). 

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The sulfenic acids have been found to be extremely active radical scavengers showing rate constants of at least 107 m"1 s 1 for the reactions with peroxyl radicals at 333 K17. It has also been suggested that the main inhibiting action of dialkyl sulfoxides or related compounds in the autoxidation of hydrocarbon derives from their ability to form the transient sulfenic acids on thermal decomposition, i.e.17... 

Reactivity of Alcohols in Reaction with Peroxyl Radicals... 

Reactivity of Ethers in Reactions with Peroxyl Radicals References... 

Secondary hydroperoxides are decomposed in oxidizing hydrocarbons in the chain reaction with peroxyl radicals [138]. 

We observe the sufficiently higher activity of H02VH0R02 radicals in their reactions with alcohols than that of R OO. The next section will be devoted to detailed analysis of alcohol reactivity in reactions with peroxyl radicals. 

Along with tertiary hydroperoxide of ether, the BDE of the O—H bonds of alkoxy hydroperoxides are higher than that of similar hydrocarbons. Very valuable data were obtained in experiments on ether oxidation (RiH) in the presence of hydroperoxide (RiOOH). Peroxyl radicals of oxidized ether exchange very rapidly to peroxyl radicals of added hydroperoxide ROOH and only R02 reacts with ether (see Chapter 5). The rate constants of alkylperoxyl radicals with several ethers are presented in Table 7.18. The reactivity of ethers in reactions with peroxyl radicals will be analyzed in next section. 

Like for aldehydes, two factors are important for the reactivity of ketones in reactions with peroxyl radicals reaction enthalpy and polar interaction. The enthalpy of the reaction of the peroxyl radical with ketone is AH = DC—a A> H- The BDE of the a-C—H bonds of ketones are lower than those of the C—H bonds of the hydrocarbons (see Table 8.11) and the BDEs of the O—H bonds in a-ketohydroperoxides are marginally higher than those of alkylhydroperoxides. Therefore, the enthalpies of R02 + RH reactions are lower than those of parent hydrocarbons (Table 8.15). 

Therefore, the polar group influences the reactivity of ester in reactions with peroxyl radicals (see later). Due to the polar groups, the effect of multidipole interaction was observed in reactions of polyesters with R02 , 02, and ROOH (see Section 9.3.4). Ester as a polar media solvates the polar TS and influences the reactivity of polar reagents. 

Antioxidants that break chains by reactions with peroxyl radicals. These are reductive compounds with relatively weak O—H and N—H bonds (phenols, naphthols, hydro-quinones, aromatic amines, aminophenols, diamines), which readily react with peroxyl radicals forming intermediate radicals of low activity. 

For an antioxidant that breaks chains by the reaction with peroxyl radical according to the reactions ... 

With 2,4,6-trialkylphenols used as inhibitors, the formed phenoxyl radicals produce quinolide peroxides by the reactions with peroxyl radicals. At sufficiently high temperatures, quinolide peroxides decompose giving rise to free radicals [18,31,32,53,54] ... 

This problem was first approached in the work of Denisov [59] dealing with the autoxidation of hydrocarbon in the presence of an inhibitor, which was able to break chains in reactions with peroxyl radicals, while the radicals produced failed to contribute to chain propagation (see Chapter 5). The kinetics of inhibitor consumption and hydroperoxide accumulation were elucidated by a computer-aided numerical solution of a set of differential equations. In full agreement with the experiment, the induction period increased with the efficiency of the inhibitor characterized by the ratio of rate constants [59], An initiated inhibited reaction (vi = vi0 = const.) transforms into the autoinitiated chain reaction (vi = vio + k3[ROOH] > vi0) if the following condition is satisfied. 

Phenols decrease the intensity of CL 7chi in oxidized hydrocarbons as a result of chain termination by the reaction with peroxyl radicals. Since Icu [R02 ]2 (see Chapter 2), the ratio (/0//)12 was found to be proportional to [ArOH] [7]. The kinetic isotope effect (k0K/k0n 1) proves that the peroxyl radical abstracts a hydrogen atom from the O—H bond of phenol [2,8]. 

Polar solvents block the O—H bond of phenols in the reaction with peroxyl radicals due to the formation of hydrogen bond and decrease the activity of phenols as chain terminating agents [1,9,10]. 

We came across the influence of the steric factor earlier when discussing the difference in the reactivities of sterically nonhindered phenols (Ar OH) and sterically hindered phenols (Ar2OH) in their reactions with peroxyl radicals. The same factor, namely, the influence of... 

Nitro compounds, like quinones, terminate chains in oxidizing compounds where hydroperoxyl radicals are formed. This was proved for the oxidation of polyatomic esters [37] and PP [38], Nitrobenzene retards the initiated oxidation of the following esters tetrapropionate of pentaerythritol, propionate of 2,2-dimethylbutanol, and dipropionate of 2,2-dimethylpro-panediol terminating chains by the reaction with peroxyl radicals [37]. The hydroperoxyl radicals were supposed to be formed as a result of the following reactions ... 

Aryl phosphites inhibit the initiated oxidation of hydrocarbons and polymers by breaking chains on the reaction with peroxyl radicals (see Table 17.3). The low values of the inhibition coefficient / for aryl phosphites are explained by their capacity for chain autoxidation [14]. Quantitative investigations of the inhibited oxidation of tetralin and cumene at 338 K showed that with increasing concentration of phosphite /rises tending to 1 [27]. 

The mechanism of inhibitory action of aryl phosphites seems to be relatively complex. Phosphites reduce hydroperoxide and thus decrease chain autoinitiation. The formed peroxyl and alkoxyl radicals react with phosphites to form aroxyl radicals. The latter terminates the chains by reaction with peroxyl radicals. On the other hand, phosphites are hydrolyzed with... 

The effectiveness of complexes metal-acetylacetonate with tris(l,l-dimethylethyl-4-methylphenyl) phosphite in their reaction with peroxyl radicals of styrene and tetralin (323 K) decreases in the row Co2+ > V02+ > Cr3+ > Fe2+ [88]. 

In this reaction, a-tocopherol is regenerated at the expense of the ionoxyl radical. Rapid cross-disproportionation diminishes the total concentration of phenoxyl radicals (thereby preventing their participation in chain propagation) and reduces the reactive phenol (a-tocopherol is more reactive toward ROOH than ionol) into methylenequinone, which terminates the chains in the reaction with peroxyl radicals. 

As mentioned earlier, when NO concentration exceeds that of superoxide, nitric oxide mostly exhibits an inhibitory effect on lipid peroxidation, reacting with lipid peroxyl radicals. These reactions are now well studied [42-44]. The simplest suggestion could be the participation of NO in termination reaction with peroxyl radicals. However, it was found that NO reacts with at least two radicals during inhibition of lipid peroxidation [50]. On these grounds it was proposed that LOONO, a product of the NO recombination with peroxyl radical LOO is rapidly decomposed to LO and N02 and the second NO reacts with LO to form nitroso ester of fatty acid (Reaction (7), Figure 25.1). Alkoxyl radical LO may be transformed into a nitro epoxy compound after rearrangement (Reaction (8)). In addition, LOONO may be hydrolyzed to form fatty acid hydroperoxide (Reaction (6)). Various nitrated lipids can also be formed in the reactions of peroxynitrite and other NO metabolites. 

Antioxidant activity of flavonoids has already been shown about 40 years ago [90,91]. (Early data on antioxidant flavonoid activity are cited in Ref. [92].) Flavonoids are polyphenols, and therefore, their antioxidant activity depends on the reactivity of hydroxyl substituents in hydrogen atom abstraction reactions. As in the case of vitamins E and C, the most studied (and most important) reactions are the reactions with peroxyl radicals [14], hydroxyl radicals [15], and superoxide [16]. 

Enes et al. (2006) recently presented new fulleropyrrolidines bearing one or two 3,5-di-tert-bvAy 1-4-hydroxyphcny 1 units, the EPR studies of which demonstrated that these derivatives are antioxidants. In this case, the presence of the fullerene unit seems to play a marginal role in the reaction with peroxyl radicals, which is governed by the phenol portion. Despite this, the presence of C60 should contribute to scavenge radicals in hypoxic conditions, where alkyl radicals could be the main oxidative products to be removed. 

Antioxidants are compounds that inhibit autoxidation reactions by rapidly reacting with radical intermediates to form less-reactive radicals that are unable to continue the chain reaction. The chain reaction is effectively stopped, since the damaging radical becomes bound to the antioxidant. Thus, vitamin E (a-tocopherol) is used commercially to retard rancidity in fatty materials in food manufacturing. Its antioxidant effect is likely to arise by reaction with peroxyl radicals. These remove a hydrogen atom from the phenol group, generating a resonance-stabilized radical that does not propagate the radical reaction. Instead, it mops up further peroxyl radicals. In due course, the tocopheryl peroxide is hydrolysed to a-tocopherylquinone. 

Valcic, S., Burr, J.A., Liebler, D.C., and Timmermann, B.N., Antioxidant chemistry of green tea catechins. Identification of products of the reaction of (—)-pigallocatechin gallate and (—)-epigallocatechin from their reactions with peroxyl radicals, Chem. Res. Toxicol, 13, 801, 2000. 

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