Hydroxyl radicals, abstraction reactions

Figure 2-17. Lipid peroxidation. A hydroxyl radical abstracts a hydrogen from a fatty acid or lipid molecule. After rearrangement to a conjugated structure, the radical reacts with oxygen to form a peroxyl radical. The newly formed peroxyl radical can initiate a chain reaction whereby new peroxyl radicals are formed.

Phulkar S, Rao BSM, Schuchmann H-P, von Sonntag C (1990) Radiolysis of tertiary butyl hydroperoxide in agueous solution. Reductive cleavage by the solvated electron, the hydrogen atom, and, in particular, the superoxide radical anion. Z Naturforsch 45b 1425-1432 Pross A, Yamataka H, Nagase S (1991) Reactivity in radical abstraction reactions - application of the curve crossing model. J Phys Org Chem 4 135-140 Rao PS, Flayon E (1975) Reaction of hydroxyl radicals with oligopeptides in aqueous solutions. A pulse radiolysis study. J Phys Chem 79 109-115... 

The attack on the aromatic nucleus by hydroxyl radicals is probably analogous to that by phenyl and methyl radicals, Eq. (34a,b). Evidence that the first step is the addition of hydroxyl radical to benzene, rather than abstraction of a hydrogen atom, has recently been adduced from a study of the radiolysis of water-benzene mixtures. The familiar addition complex may undergo two reactions to form the phenolic and dimeric products respectively, Eq. (34a,b). Alternative mechanisms for the formation of the dimer have been formulated, but in view of the lack of experimental evidence for any of the mechanisms further discussion of this problem is not justified. 

Hydroxy radical and sulfate radical anion, though they may sometimes give rise to similar products, show quite different selectivity in their reactions with unsaturated substrates. In particular, the sulfate radical anion has a somewhat lower propensity for hydrogen abstraction than the hydroxyl radical. For example, the sulfate radical anion shows little tendency to abstract hydrogen from mcthacrylic acid.232... 

NMHC. A large number of hydrocarbons are present in petroleum deposits, and their release during refining or use of fuels and solvents, or during the combustion of fuels, results in the presence of more than a hundred different hydrocarbons in polluted air (43,44). These unnatural hydrocarbons join the natural terpenes such as isoprene and the pinenes in their reactions with tropospheric hydroxyl radical. In saturated hydrocarbons (containing all single carbon-carbon bonds) abstraction of a hydrogen (e,g, R4) is the sole tropospheric reaction, but in unsaturated hydrocarbons HO-addition to a carbon-carbon double bond is usually the dominant reaction pathway. 

The stability of perchlorofluoroalkanes is due to the absence of hydrogen atoms that may be abstracted by reaction with hydroxyl radicals. Attention has therefore been directed to chlorofluo-roalkanes containing at least one hydrogen atom (Hayman and Derwent 1997). Considerable effort has also been directed to the reactions of chloroalkanes and chloroalkenes, and this deserves a rather more detailed examination in the light of interest in the products that are formed. 

Radicals can react with bases via hydrogen atom abstraction or, more commonly, by addition to the pi bonds in the heterocyclic nucleobases (Scheme 8.1). These reactions have been extensively studied in the context of hydroxyl radical (HO ), which is generated by y-radiolysis of water. When DNA is exposed to the hydroxyl radical, approximately 80% of the reactions occur at the bases. Many base damage products arising from the reaction hydroxyl radical with DNA have been characterized (Fig. 8.2). ... 

This conclusion is partly true because superoxide is unable to abstract hydrogen atom even from the most active bisallylic positions of unsaturated compounds, while perhydroxyl radical abstracts H atom from linoleic, linolenic, and arachidonic fatty acids with the rate constants of 1-3 x 1031 mol-1 s-1 [24], However, the superoxide damaging activity does not originate from hydrogen atom abstraction reactions but from one-electron reduction processes, leading to the formation of hydroxyl radicals, peroxynitrite, etc, and in these reactions perhydroxyl cannot compete with superoxide. 

Iron complexes or microsomal nonheme iron are undoubtedly obligatory components in the microsomal oxidation of many organic compounds mediated by hydroxyl radicals. In 1980, Cohen and Cederbaum [27] suggested that rat liver microsomes oxidized ethanol, methional, 2-keto-4-thiomethylbutyric acid, and dimethylsulfoxide via hydrogen atom abstraction by hydroxyl radicals. Then, Ingelman-Sundberg and Ekstrom [28] assumed that the hydroxylation of aniline by reconstituted microsomal cytochrome P-450 system is mediated by hydroxyl radicals formed in the superoxide-driven Fenton reaction. Similar conclusion has been made for the explanation of inhibitory effects of pyrazole and 4-methylpyrazole on the microsomal oxidation of ethanol and DMSO [29],... 

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]. 

Ionizing radiations (a, ft and y) react unselectively with all molecules and hence in the case of solutions they react mainly with the solvent. The changes induced in the solute due to radiolysis are consequences of the reactions of the solute with the intermediates formed by the radiolysis of the solvent. Radiolysis of water leads to formation of stable molecules H2 and H2O2, which mostly do not take part in further reactions, and to very reactive radicals the hydrated electron eaq, hydrogen atom H" and the hydroxyl radical OH" (equation 2). The first two radicals are reductants while the third one is an oxidant. However there are some reactions in which H atom reacts similarly to OH radical rather than to eaq, as e.g. abstraction of an hydrogen atom from alcohols, addition to a benzene ring or to an olefinic double bond, etc. 

The O-dealkylation of ethers, while not as frequently encountered as N-dealkylation in drug metabolism studies, is still a common metabolic pathway. Mechanistically it is less controversial than N-dealkylation in that it is generally believed to proceed by the HAT pathway, i.e., a-hydrogen atom abstraction followed by hydroxyl radical rebound, and not a SET pathway (Fig. 4.58). The product of the reaction is unstable, being a hemiacetal or hemiketal depending on the number of hydrogens on the a-carbon, which dissociates to generate an alcohol and an aldehyde or ketone. 

The hydroxyl radicals formed may abstract hydrogen from the cellulose fiber substrate which gives grafting sites and subsequently grafted polymer with monomer present. The HO- radicals may also initiate homopolymerization. This means that reaction (17) is not specific for initiation of grafting. Another disadvantage is that the Fe + ions formed - if not carefully removed -may cause discoloration of the resulting product. 

It should additionally be noted that a number of the paths of the schemes above have received some confirmation in a number of literature reports dealing with the photolysis and photo-oxidation of other polyesters [32-35], Because these reports investigated poly(butylene terephthalate) (PBT), poly(ethylene naphthalate) and poly(butylene naphthalate), however, they may not have direct application to understanding of the processes involved in PET and PECT and so have not been discussed in this present chapter. All do contain support for the formation of radicals leading to CO and C02 evolution, as well as the hydrogen abstraction at glycolic carbons to form hydroperoxides which then decompose to form alkoxy radicals and the hydroxyl radical. These species then were postulated to undergo further reaction consistent with what we have proposed above. 

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