Synthesis, Characterization, Cytotoxicity and DNA/BSA Interaction of Pd(II) Complexes with Alkyl-Amine and 1,10-Phenanthroline

A novel series of Pd(II) complexes, [Pd(alkyl-amine)₂(phen)](NO₃)₂, I-V, (where alkylamine is ethyl-, propyl-, butyl-, hexyl- and octyl-amine and phen is 1,10-phenanthroline) were synthesized and characterized based on FT-IR, ¹H NMR, COSY-NMR, UV-Vis, molar conductivity, elemental analysis and density functional theory (DFT) approaches. The group, I-V, was screened for their primary in-vitro cytotoxic action against human cancer cell line MOLT-4, showing promising anti-tumor activities. Their interaction activity was tested using various spectroscopic techniques to explain the mode of binding between these compounds with CT-DNA and BSA. Results of UV-Vis studies showed that, at low concentrations, they all interacted effectively with CT-DNA and BSA. Studies of fluorescence emission spectra displayed that the complexes quenched CT-DNA pretreated with methylene blue (MB) and the intrinsic fluorescence of BSA via static quenching. Using thermodynamic parameters (ΔG°, ΔH°, and ΔS°) obtained from fluorescence studies, it was proposed that the hydrogen bonding and van der Waals forces play the main role between metal complexes with CT-DNA and BSA. The binding was spontaneous in all cases due to ΔG° <0. Also, Molecular docking simulation of all five Pd(II) complexes with DNA was performed to determine the compound with the highest binding affinity and investigate its binding mode. Next, molecular docking was utilized for this compound to study its BSA binding mode and affinity. The results obtained from this work may lay the foundation for structural changes exerted on DNA and BSA by Pd(II) antitumor compounds bearing various hydrocarbon chain length as well as structural relationship which are vital for pharmacokinetic and pharmacodynamics.