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.

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-Me3 U) or 1,3-dimethylthymine (1,3-Me2 T) were irradiated with 60Co gamma rays; the sulphate radical formed by the reaction of the solvated electron with peroxodisulphate oxidizes these pyrimidines. In the case of 1,3,6-Me3 U, 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 x 10(-4) mol dm-3 1,3,6-Me3 U, 4 x 10(-2) mol dm-3 S2O8(2-) and 10(-2) mol dm-3 tert-BuOH with a dose-rate of 2.2 x 10(-3) Gy s-1, G(H+) is 220 x 10(-7) mol J-1. We believe that the sulphate radical adds to the 1,3,6-Me3 U and the adduct rapidly loses the sulphate dianion, giving rise to the 1,3,6-Me3 U 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-Me2 T 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 x 10(-7) mol J-1) and 1,3-dimethyl-5-hydroxymethyluracil (G = 0.2 x 10(-7) mol J-1). As the corresponding products are not observed in the 1,3,6-Me3 U system, it is concluded that in contrast to the 1,3,6-Me3 U radical cation, the 1,3-Me2 T 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-Me2 T 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-Me2 T and 1,3,6-Me3 U should differ in their behaviour.(ABSTRACT TRUNCATED AT 250 WORDS)