Structure and tautomeric properties of thymine derivatives generated by hydroxyl radical in aerobic conditions

The tautomeric properties of five hydroxyl radical-induced thymine derivatives: thymine glycol (1), 5-formyldeoxyuracil (2), 5-hydroxymethyluracil (3), N-tatronyluridine (4) and 5-hydroxymethylhydantoine (5) were characterised by ab initio HF (6-311G**), MP2 (6-311G**) and SCI-PCM (6-311G**) quantum chemistry calculations. Amongst all the tautomers of 1 the I-5eq6ax tautomer (the diketo form with C-5 equatorial and C-6 axial orientations of the hydroxy groups) is the most stable, in both polar and non-polar environments. The most stable tautomer of 2 is the diketo form with the carbonyl group oriented in such a way that the maximum distance between O-4 and O-C'5 oxygen atoms is preserved. By analogy, the preferred tautomeric form of 3 corresponds to the diketo isomer. Among the potential 43 isomers of 4 the most stable is that in the diketo-amino form with anti-conformation of the C-2-N-3-C-4-C-5 torsion angle and equatorial conformation of the C-5 chirality centre. Finally, the most probable structure of 5 is the diketo tautomeric form.