By Superoxide, Peroxy Radicals and Peroxide

A second important point to note is that the reactions that will be subsequently described are not exclusively restricted to DNA bases. Indeed, RNA is also subject to oxidative damage where oxidised bases released into the cytoplasmic pool by repair processes may be subsequently incorporated into nucleic acids during de novo nucleic acid synthesis. 

The methyl group of thymine is susceptible to hydrogen abstraction resulting in a carbon-centred allyl radical. Further oxidation of this radical intermediate can yield thymine-specific products, 5-hydroxymethyluracil and 5-formyluracil. Cytosine adducts also yield unique products under further 

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The reactivity of 02 - with alkyl halides in aprotic solvents occurs via nucleophilic substitution. Kinetic studies confirm that the reaction order is primary > secondary > tertiary and I > Br > Cl > F for alkyl hahdes, and that the attack by 02 - results in inversion of configuration (Sn2). Superoxide ion also reacts with CCI4, Br(CH2)2Br, CeCle, and esters in aprotic media. The reactions are via nucleophilic attack by 02 on carbon, or on chlorine with a concerted reductive displacement of chloride ion or alkoxide ion. As with all oxyanions, water suppresses the nucleophilicity of 02 (hydration energy, lOOkcalmoL ) and promotes its rapid hydrolysis and disproportionation. The reaction pathways for these compounds produce peroxy radical and peroxide ion intermediates (ROO and ROO ). 

The reaction stoichiometries, product profiles, and apparent second-order rate constants for the combination of perfluoroaromatic molecules (and several hydro and dihydro derivatives) with excess superoxide ion in dimethylformamide are summarized in Table 7-1. The primary product from the combination of C6F6 with 2 equivalents of O2-- is CeEgOO on the basis of the F-NMR spectrum of the product solution and the mass spectrum for the major peak from the capillary GC of the product solution.24 Similar analyses of the product solutions for the other fluoro substrates are consistent with a peroxide product from the displacement of a fluoride ion. A reasonable first step for these oxygenations is nucleophilic addition of O2 - to the polyfluoroaromatic. Subsequent loss of fluoride ion will give an aryl peroxy radical, which will be reduced by a second O2-- to the aryl peroxide product. This reaction sequence (with the initial nucleophilic displacement the rate-determining step) is analogous to that observed for chlorohydrocarbons and polychlorobenzenes (Scheme 7-8). However, the peroxo product of the latter systems is an effective nucleophile that attacks a second substrate molecule (or an adjacent aryl chlorine... 

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