Coding properties of thymine derivatives generated by hydroxyl radical in aerobic conditions

Abstract

The coding properties of three hydroxyl radical induced thymine derivatives, 5-hydroxymethyluracil, thymine glycol and 5-formyldeoxyuracil were characterised by means of abinitio HF (6-31G), HF(6-31G**/6-31G) and SCI-PCM (6-31G**/6-31G) quantum chemistry calculations. All studied derivatives may have potential miscoding character, which strongly depends on the polarity of the environment. In non-polar conditions the 5-hydroxymethyluracil is able to form pairs with guanine and adenine, thymine glycol pairs with guanine, cytosine and adenine but 5-formyldeoxyuracil is capable of forming dimers with guanine and adenine. Although all these thymine derivatives may form dimers also with other DNA bases these pairs are more stable compared to the Watson–Crick adenine–thymine pair. In polar environment the pairing potential of studied thymine derivatives may change significantly. Usually a reduction in the pairs' relative stability is observed. For all pairs the stabilisation energy becomes less than the corresponding value for the adenine–thymine pair. However the mispairing potential is still significant, especially for 5-hydroxymethyluracil.