An ab initio SCF study on the tautomerisation of the 8-oxo-guanine and xanthine

All possible Hg-tautomers of 8-oxo-guanine and xanthine were studied by means of PM3 semiempirical and DFT (density functional theory) quantum chemistry methods. Additionally, the five most stable tautomers of both guanine derivatives were estimated on 3-21G, 6-31G, 6-31G** and MP2 (6-31G**) ab initio levels. The impact of the environment polarity on the tautomeric equilibrium was also taken into account. Among the variety of tautomeric isomers most probable are diketo forms of both studied derivatives in non-polar and polar surroundings. The tautomeric equilibrium was unchanged after connection of the sugar backbone. The most preferred diketo forms of 8-oxo-guanosine and xanthidine are in syn conformations both in polar and non-polar environments. The increase of the syn conformations over anti ones may have the source in the formation of the internal hydrogen bonds between H'5 and N-3 atoms. The calculated values of the pseudorotation phase angle were between 144 and 180 degrees in all cases. This corresponds to C'2-endo conformations of all optimised structures. The N-glycosidic bond stability of most stable tautomers was compared to standard guanosine. Most tautomers of 8-oxo-guanosine and xanthidine are characterised by more stable C-1'-N-9 bond. This indicates that both these derivatives are hardly susceptible to spontaneous depurination and its removal from the DNA will depend mostly on the activity of DNA repair enzymes. (C) 1998 Elsevier Science B.V.