Site of OH Radical Attack on Dihydrouracil and Some of Its Methyl Derivatives

Summary

The site of attack of OH radicals on dihydrouracil and five of its methylated derivatives was determined by pulse radiolysis using NNN′N′-tetramethylphenylenediamine (TMPD) to detect oxidizing radicals and tetranitromethane (TNM) as well as K₃Fe(CN)₆ to detect reducing radicals. In the case of dihydrouracil OH radicals abstract preferentially an H atom at C(6) to give the 6-yl radical (≥ 90 per cent) which at pH ∼6·5 reduces TNM and K₃Fe(CN)₆ at almost diffusion-controlled rates. Only a small fraction of OH radicals abstract the H atom at C(5) (≤ 10 per cent). The resulting 5–yl radical oxidizes TMPD to TMPD⁺ at pH 7–8. With the methylated derivatives of dihydrouracil, OH radicals react less selectively, especially in the case of N(1)-methyl derivatives. This methyl group is activated to a similar degree as the methylene group at C(6). In 1-Medihydrouracil the yield of N(1)-CH·₂ radicals is about 29 per cent, which has been deduced from the yield of formaldehyde formed after oxidation of this radical by TNM at pH ∼6·5 and the subsequent hydrolysis. Radicals at the other methyl substituents are generated to a lesser extent (≤ 10 per cent) and are relatively unreactive towards oxidizing agents such as TNM and K₃Fe(CN)₆ as well as towards the reducing agent TMPD. Although methyl substitution opens new routes for OH attack the prefered site of H abstraction remains C(6) (> 60 per cent).

• pulse radiolysis
• dihydrouracil
• OH radicals