Structure and properties of hydroxyl radical modified nucleic acid components II. 8-Oxo-adenine and 8-oxo-2′-deoxy-adenosine

Abstract

The tautomerism of the 8-oxo-adenine (8-oxo-A) and 8-oxo-2′-deoxy-adenosine (8-oxo-dA) was analysed on the basis of semiempirical, SCF ab initio and DFT density functional quantum chemistry calculations. The results of full gradient geometry optimisation of all possible 8-oxo-A and 8-oxo-dA structures lead to the conclusion that the most stable form is 8-keto-6-amino-tautomer. The second stable tautomer corresponds to 8-hydroxy-isomer. Such an order was unchanged after solvating process. In all studied solvents: water, methanol, acetone, cyclohexane the keto-tautomer proceeds the enol one. The preferred N-glycoside torsion angle corresponds to syn rotamer of 8-oxo-dA in all studied cases. However, the PM3 method predicted reversed order of syn and anti conformers for 8-oxo-dA tautomer. Both tautomers have miscoding properties resulting in the formation of stable base pairs with cytosine and guanine instead of thymine (as it is in the case of canonical adenine). Despite less stability of enol tautomer the pair formed with cytosine is as much stable as pair comprising 8-oxo-tautomer. The most stabile pairs are those, where O 8 oxygen or H o8 hydrogen atoms are involved in the hydrogen bond formation. The Watson-Crick like pairs of cytosine and guanine with one of two most stable 8-oxo-A tautomer are more stable than standard A-T pairs. This may be the reason of experimentally observed AT ⇒ CG transversion or AT ⇒ GC transition.