Computational and experimental examinations of new antitumor palladium(II) complex: CT-DNA-/BSA-binding, prediction, DFT perspective, docking, molecular dynamics simulation and ONIOM.

Since the design of metal complexes with better biological activities is important, herein a new palladium(II) complex bearing en and acac (en and acac stand for ethylenediamine and acetylacetonato, respectively) as its ligands, [Pd(en)(acac)]NO complex, was synthesized and fully characterized. Quantum chemical computations of the palladium(II) complex were done DFT/B3LYP method. Cytotoxicity activity of the new compound on leukemia cell line (K562) was assessed MTT method. The findings indicated that the metal complex has remarkable cytotoxic effect than cisplatin. OSIRIS DataWarrior software was employed to calculate physicochemical and toxicity parameters of the synthesized complex which rendered significant results. To comprehend the interaction type of new metal compound with macromolecules, the in depth investigation of interaction of mentioned complex with CT-DNA and BSA was accomplished by fluorescence, UV-Visible absorption spectroscopy, viscosity measurement, gel electrophoresis, FRET analysis and circular dichroism (CD) spectroscopy. On the other hand, computational molecular docking was carried out and the obtained data demonstrated that H-bond and van der Waals forces are the dominant forces for the binding of the compound to the mentioned biomolecules. Molecular dynamics simulation was also done and confirmed the stability of best docked pose of palladium(II) complex inside DNA or BSA over the time and in presence of water solvent. Also, Our own N-layered Integrated molecular Orbital and molecular Mechanics (ONIOM) methodology based on the hybridization of quantum mechanics and molecular mechanics (QM/MM) methodology was accomplished to inquire about binding of Pd(II) complex with DNA or BSA.HIGHLIGHTSNew biologically active Pd(II) complex was synthesized and characterized.The studies of the designed complex and its ligands were accomplished by OSIRIS DataWarrior softwareInteraction with CT-DNA and BSA was assessed by various spectroscopic methods.Molecular docking simulation supported the interaction with both macromolecules.Based on ONIOM analysis, the structures of the complex and biomolecules are altered after binding. Communicated by Ramaswamy H. Sarma.