The glycosyl C-1 '-N-9 bond of deoxyadenosine and deoxyguanosine: responseto electrophilic attacks on the purinic nitrogen atoms

Self-consistent-field computations shed light on two relevant conformations of deoxyadenosine (dA) and deoxyguanosine (dG): one with a pseudoequatoria l C1'N9 glycosyl bond and the other, a slightly more stable one, with its C 1'N9 bond in a bisectional orientation. In dA, both the N-3 and N-7 nitroge ns are plausible sites for electrophilic attack, but only N-7 is a plausibl e site in dG. The addition of H+, CH3+, C2H5+ or tert-C4H9+ onto N-7 does n ot provoke notable structural modifications and leaves the base of dA and d G in an antiperiplanar (or nearly antiperiplanar) position with respect to the sugar C1'O4' bond, but N-3 additions cause the base to adopt a synperip lanar or strongly chiral position. This produces strong interactions betwee n the purine and deoxyribose moieties, whose relief could aid the eventual cleavage of the glycosyl bond of dA. addition of a radical cation onto N-7 reduces the dissociation energy of the glycosyl bond by an estimated 8 kcal mol(-1) in dA and 4 kcal mol(-1) in dG - a bond weakening likely to concur to a depurination of DNA induced by radical cations.