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 (A T) 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 p urine position have been investigated using advanced quantum chemical metho ds. The molecular complexes were optimized using Becke3LYP density function al theory (DFT) approach. For each base pair we evaluated two structures, o ne 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 t he purine nucleobase. Interaction energies were evaluated and decomposed in to individual pairwise and many-body terms. For some systems, the Becke3LYP approach provided biased interaction energy decomposition when including t he correction for the basis set superposition error. Thus, these systems we re re-evaluated with a second-order Moller-Plesset (MP2) perturbation appro ach resulting in correct decomposition. The calculations show, among other results, that the GC base pair is significantly strengthened by polarizatio n effects when Pt(NH3)(3)(2+) is bound to its N-7 position. This observatio n 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-she ll binding of hydrated divalent cations of zinc and magnesium groups.