cis-[Pt(NH3)(2)](2+) coordination to the N7 and O6 sites of a guanine-cytosine pair: disruption of the Watson-Crick H-bonding pattern

The coordination of cis-[Pt(NH3)(2)](2+) to the N7 and O6 sites of guanine of the guanine-cytosine (GC) nucleic base pair is studied at the SCF, DFT a nd MP2 levels of theory, and by an ab initio BSSE-free optimization algorit hm, concerning the possible mechanisms of the antitumor activity of cis-[Pt (NH3)(2)Cl-2]. The calculations show that the cis-[Pt(NH3)(2)](2+) coordina tion results in the breakage of the (cytosine)N4-H-O6(guanine) H-bond and a substantial non-planarity of the GC moiety. From an analysis of the electr ostatic potential at the O6, N1-H and N2-H sites of cis-[Pt(NH3)(2)G](2+) w e can explain the predicted changes in geometry and binding energy of the G C complex. (C) 1999 Elsevier Science B.V. All rights reserved.