Design, synthesis, characterization, cytotoxicity, molecular docking and analysis of binding interactions of novel acetylacetonatopalladium(ii) alanine and valine complexes with CT-DNA and BSA

Abstract

To enhance the development of potential anti-tumor agents, a pair of new, water-soluble and neutral acetylacetonatopalladium(II) complexes with alanine and valine amino acids have been synthesized. They were characterized by elemental analysis (C, H, N), FT-IR, UV-Vis, resonance signals in the ¹H-NMR, ESI-MS and conductivity measurements. The molecular geometry, the energy level of the frontier orbitals and the NMR chemical shift values of the Pd(II) complexes have been calculated by using B3LYP/LANL2DZ method and 6-311g* basis set. Cytotoxicity effects of the complexes towards cancer cell line of K₅₆₂ were measured using MTT assay. The interactions of these complexes with calf thymus DNA (CT-DNA) and Bovine Serum Albumin (BSA) were investigated under physiological condition in Tris–HCl buffer pH = 7 containing 0.02 M sodium chloride using spectroscopic methods including UV-Vis absorption spectroscopy, ethidium bromide displacement, fluorescence titration spectra and viscosity measurements. The results obtained from these analyses indicated that both complexes effectively interact with CT-DNA and BSA at low concentrations. Fluorescence titration revealed that the complexes strongly quench DNA bound ethidium bromide (EB) as well as the intrinsic fluorescence of BSA through static quenching procedures. Binding constant (K_b), apparent bimolecular quenching constant (K_q) and number of binding sites (n) for CT-DNA and BSA were calculated using Stern–Volmer equation. Also, thermodynamic parameters data suggested that hydrogen binding and van der Waals force play a major role in the association of CT-DNA–Pd(II) and BSA–Pd(II) complex formation and follow the binding affinity order of valine complex > alanine complex. The complexes exhibited groove binding with CT-DNA and interact with main binding pocket of BSA. In both cases the binding forces are spontaneous owing to −ΔG°. Finally, the results of molecular docking calculations of [Pd(acac)(Ala)] and [Pd(acac)(Val)] complexes for CT-DNA and BSA clarify the binding modes and binding sites which are in good accordance with experimental results.