The influence of square planar platinum complexes on DNA base pairing.: An ab initio DFT study

The energetics and structures of guaninecytosine (GC) and adeninethymine (AT) Watson-Crick base pairs metalated by the square planar platinum adducts and at trans-PtCl2(NH3), trans-PtCl(NH3)(2)(+) and Pt(NH3)(3)(2+) the N-7 purine position have been investigated using advanced quantum chemical methods. The molecular complexes were optimized using Becke3LYP density functional theory (DFT) approach. For each base pair we evaluated two structures, one of them with and the other without the formation of intrasystem H bonds between the ligands attached to the metal and the exocyclic 6 position of the purine nucleobase. Interaction energies were evaluated and decomposed into individual pairwise and many-body terms. For some systems, the Becke3LYP approach provided biased interaction energy decomposition when including the correction for the basis set superposition error. Thus, these systems were re-evaluated with a second-order Moller-Plesset (MP2) perturbation approach resulting in correct decomposition. The calculations show, among other results, that the GC base pair is significantly strengthened by polarization effects when Pt(NH3)(3)(2+) is bound to its N-7 position. This observation is in agreement with recent solution experiments on platinated base pairs. The calculations suggest that the effect exerted by Pt(NH3)(3)(2+)on the base pair stability is larger compared with the effect exerted by inner-shell binding of hydrated divalent cations of zinc and magnesium groups.