The interactions of square platinum(II) complexes with guanine and adenine: A quantum-chemical ab initio study of metalated tautomeric forms

The influence of binding of square planar platinum complexes on tautomeric equilibria of the DNA bases guanine and adenine was investigated using the density functional B3LYP method. Neutral trans-dichloro(amine)-, +1 charged chloro(diamine)-, and +2 charged triamine-platinum(II) species were chosen for coordination to bases. Only the N-7 interaction site of the bases was considered. The calculations demonstrate that the neutral platinum adduct d oes not change the tautomeric equilibria of the bases. Furthermore, NI bind ing of the neutral Pt adduct moderately reduces the probability of protonat ion of the N-1 position of adenine. Larger effects can be observed for +1 a nd mainly +2 adducts, but these can be rationalized by electrostatic effect s. Since the electrostatic effects are expected to be efficiently compensat ed for by a charged backbone of DNA and counterions in a polar solvent, no dramatic increase in mispair formation is predicted for Pt(II) adducts, whi ch is in agreement with experiment. The interaction energies between Pt add ucts and the nucleobases were also evaluated. These interaction energies ra nge from ca. 210 kJ/mol for neutral adducts, interacting with both bases an d their tautomers, up to 500 kJ/mol for the +2 charged adducts, interacting with the keto-guanine tautomer and the anti-imino-adenine tautomer. The su rprisingly large interaction energy for the latter structure is due to the strong H-bond between the NH3 ligand group of the metal adduct and the N-6 nitrogen atom of the base.