An ab initio study of the tautomeric and coding properties of 8-oxo-guanine

Self-consistent field (SCF) and density function theory (DFT) ab initio calculations of 8-oxo-guanine, 8-oxo 2'-deoxyguanosine and their pairing properties with canonical nucleic acid bases have been performed. The 6,8-diketo-form of 8-oxo-G was predicted to be the most stable tautomer among all possible H-9 potential structures. The relative stability of the tautomers remains the same after immersion in solvents of different polarity. The tautomeric properties of 8-oxo 2'-deoxyguanosine were the same as those of 8-oxo-G. The syn-conformations of all tautomers of nucleosides were preferred over the anti-ones, both in vacuum and in aqueous solution. The pairing potential of 8-oxo-G was estimated by means of DFT and SCF calculations. This guanine derivative has a high mispairing potential, which was strongly dependent on its tautomeric form. The 6,8-diketo-isomer of 8-oxo-G may form many different pairs but those with cytosine and guanine are more stable than the standard GC pair. The 6-enol-8-keto tautomer may also be involved in a variety of dimers, but pairs with thymine and adenine are more favoured than standard GC ones. Moreover, the less favoured tautomers such as 6-enol-2-imino or 6,8-dienol-2-imino, were also potentially able to pair with cytosine and guanine. Despite the lower stability of the tautomers, the resulting pairs are characterised by higher energy than the standard GC pair. The same conclusions may be drawn after calculations in the presence of an electrostatic held of water. The good pairing with cytosine is not surprising, due to the great geometric and electrostatic similarities between the 6,8-diketo form of 8-oxo-G and standard guanine. However, very stable dimers with guanine and thymine, if they occur in the DNA interior, may be responsible for the GC --> CG transversion and GC --> AT transition. These results are in good agreement with some in vivo and in vitro experimental observations. The source of such mutations may be related not only to the miscoding potential of the dominant tautomer, but also to that of other, less stable, tautomers of 8-oxo-G.