SO^·−₄-induced Oxidation of 1,3,6-trimethyluracil and 1,3,5-trimethyluracil (1,3-dimethylthymine) by Potassium Peroxodisulphate in Aqueous Solution: An Interesting Contrast

Summary

In order to mimic the direct effect of ionizing radiation on DNA, deoxygenated aqueous solutions of potassium peroxodisulphate, tert-butanol and 1,3,6-trimethyluracil (1,3,6-Me₃U) or 1,3-dimethylthymine (1,3-Me₂T) were irradiated with ⁶⁰Co γ rays; the sulphate radical formed by the reaction of the solvated electron with peroxodisulphate oxidizes these pyrimidines. In the case of 1,3,6-Me₃U, a chain reaction results in the formation of sulphuric acid, the glycols (two thirds) and 1,3,6-trimethylisobarbituric acid (one third). Typically, at 5 × 10⁻⁴ mol dm⁻³ 1,3,6-Me₃U, 4 × 10⁻² mol dm⁻³ S₂O²⁻₈ and 10⁻² mol dm⁻³ tert-BuOH with a dose-rate of 2·2 × 10⁻³ Gys⁻¹, G(H⁺) is 220 × 10⁻⁷ mol J⁻¹. We believe that the sulphate radical adds to the 1,3,6-Me₃U and the adduct rapidly loses the sulphate dianion, giving rise to the 1,3,6-Me₃U radical cation. This reacts with water, yielding a proton and the reducing 1,3,6-Me₃U C(5)-OH,C(6)-yl radical, which reacts with peroxodisulphate and so propagates the chain. In this oxidation process a carbocation is formed which can either react with water yielding the glycols, or deprotonate yielding the 1,3,6-trimethylisobarbituric acid. The 1,3-Me₂T system behaves differently. No chain reaction of any significance is induced. In the presence of oxygen an allyl-type radical can be trapped, as shown by the subsequent formation of 1,3-dimethyl-5-formyluracil (G = 2·1 × 10⁻⁷ mol J⁻¹) and 1,3-dimethyl-5-hydroxymethyluracil (G = 0·2 × 10⁻⁷ mol J⁻¹). As the corresponding products are not observed in the 1,3,6-Me₃U system, it is concluded that in contrast to the 1,3,6-Me₃U radical cation, the 1,3-Me₂T radical cation efficiently deprotonates (at C⁵-methyl), apart from also being able to react with water. In basic solution, OH⁻ adds to the 1,3-Me₂T radical cation, thereby suppressing the formation of the allyl-type radical. Quantum-chemical model calculations on uracil, thymine and 6-methyluracil show why 1,3-Me₂T and 1,3,6-Me₃U should differ in their behaviour. The C(5)-methyl substituted radical cation should differ from the C(6)-methyl substituted cation in the following respects: (1) the tendency to undergo deprotonation should be greater for the methyl group substituted at C(5) than at C(6); (2) the reactivity regarding water addition (to form the OH-adduct radical) should be greater in the case of the C(6)-methyl compound than for the thymine compound; and (3) the selectivity in favour of addition at C(5) versus C(6) should be greater in the case of the C(6)-methyl compound than in the substituted thymine.