DFT-molecular modeling analysis of C–H⋯N and C–H⋯S hydrogen bond type interactions in selected platinum–purine/pyrimidine complexes

Abstract

A molecular modeling analysis has been performed via density functional theory (DFT) on selected Pt(II) complexes of guanine ( G), cytosine ( C), 6-thiopurine ( TP) both as isolate molecules and aggregates of two molecules with the aim to investigate specific not-Watson–Crick pairing between nucleobases involved in the coordination to the metal, primarily from a structural point of view. The optimized structure models for the single molecules and the aggregates are in acceptable agreement with the structures found at the solid state via X-ray diffraction and reported previously in several papers. Computation performed at B3LYP/(Lanl2DZ, Pt; 6-31G, CHNO; 6-31G**, Cl) level on { cis-[PtCl(NH 3) 2( G–H 1)]⋯ C} have H 2NH⋯O( G–H 1) (2.595 Å) and ( G–H 1)C 8⋯Cl (3.213 Å) intramolecular H-bonds, and ( C)N 4⋯O( G–H 1) (2.875 Å) and (C)C 5⋯N 1( G–H 1) (3.597 Å) intermolecular H-bonds, these latter forming the base pair. The computed formation energy is ca. −13.7 kcal. On releasing the intramolecular H-bonds between the ammino ligand and O( G–H 1), and ( G–H 1)C 8–H and chloride ligand, the aggregate formation energy changes to ca. −16.9 kcal. In the case the pairing is computed by using the 6-311G** basis set for all atoms (excluding Pt) the ( C)N 4⋯O( G–H 1) and ( C)C5⋯N 1( G–H 1) contact distances are 2.929 and 3.718 Å, respectively. This shows a light overestimation of the strength of pairing between platinum–N 7-coordinated guaninato and cytosine in the case the simpler basis set (6-31G) is used. The same computational method at 6-311G** level for all C,H,N, and S atoms involved in pairing was used to predict the structures of the adduct { cis-[Pt(NH 3) 2( N 7, S– TP–H 1)] +⋯ TP} that is stabilized by ( TP)(N 1)H⋯N 1[Pt(NH 3) 2( N 7, S– TP–H 1)] and ( TP)S⋯H 2[Pt(NH 3) 2( N 7, S– TP–H 1)] hydrogen bonds. The ( TP)N 1⋯N 1( TP–H 1) and ( TP)S⋯H 2( TP–H 1) distances in the optimized adduct are 3.083 and 3.646 Å. The sulfur atom of free thiopurine has a significant accepting ability from the H–C 2 function of chelating thiopurinato. This piece of work suggests that the cis-Pt(NH 3) 2 function has significant affinity for DNA marked with TP such as that that forms after treatment of patients with the widely used anti-leukemic drug.