DFT-Molecular Modeling Analysis of C-H…N and C-H…S Hydrogen Bond Type Interactions in Selected Platinum-Purine/Pyrimidine Complexes

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(NH3)2(G-H1)]⋯C} have H2NH⋯O(G-H1) (2.595 Å) and (G-H1)C8⋯Cl (3.213 Å) intramolecular H-bonds, and (C)N4⋯O(G-H1) (2.875 Å) and (C)C5⋯N1(G-H1) (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-H1), and (G-H1)C8-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)N4⋯O(G-H1) and (C)C5⋯N1(G-H1) contact distances are 2.929 and 3.718 Å, respectively. This shows a light overestimation of the strength of pairing between platinum-N7-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(NH3)2(N7,S-TP-H1)]+⋯TP} that is stabilized by (TP)(N1)H⋯N1[Pt(NH3)2(N7,S-TP-H1)] and (TP)S⋯H2[Pt(NH3)2(N7,S-TP-H1)] hydrogen bonds. The (TP)N1⋯N1(TP-H1) and (TP)S⋯H2(TP-H1) 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-C2 function of chelating thiopurinato. This piece of work suggests that the cis-Pt(NH3)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