STRUCTURE AND PROPERTIES OF HYDROXYL RADICAL MODIFIED NUCLEIC-ACID COMPONENTS .2. 8-OXO-ADENINE AND 8-OXO-2'-DEOXY-ADENOSINE

The tautomerism of the 8-oxo-adenine (8-oxo-A) and 8-oxo-2'-deoxy-aden osine (8-oxo-dA) was analysed on the basis of semiempirical, SCF ab in itio and DFT density functional quantum chemistry calculations. The re sults of full gradient geometry optimisation of all possible 8-oxo-A a nd 8-oxo-dA structures lead to the conclusion that the most stable for m is 8-keto-6-amino-tautomer. The second stable tautomer corresponds t o 8-hydroxy-isomer. Such an order was unchanged after solvating proces s. 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. Ho wever, the PM3 method predicted reversed order of syn and anti conform ers for 8-oxo-dA tautomer. Both tautomers have miscoding properties re sulting in the formation of stable base pairs with cytosine and guanin e instead of thymine (as it is in the case of canonical adenine). Desp ite less stability of enol tautomer the pair formed with cytosine is a s much stable as pair comprising 8-oxo-tautomer. The most stabile pair s are those, where O-8 oxygen or H-O8 hydrogen atoms are involved in t he hydrogen bond formation. The Watson-Crick like pairs of cytosine an d 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 obs erved AT double right arrow CG transversion or AT double right arrow G C transition. (C) 1997 Elsevier Science B.V.