Synthesis, characterization and biological application of four novel metal-Schiff base complexes derived from allylamine and their interactions with human serum albumin: Experimental, molecular docking and ONIOM computational study.

Novel metal-based drug candidate including VOL2, NiL2, CuL2 and PdL2 have been synthesized from 2-hydroxy-1-allyliminomethyl-naphthalen ligand and have been characterized by means of elemental analysis (CHN), FT-IR and UV-vis spectroscopies. In addition, (1)H and (13)C NMR techniques were employed for characterization of the PdL2 complex. Single-crystal X-ray diffraction technique was utilized to characterise the structure of the complexes. The Cu(II), Ni(II) and Pd(II) complexes show a square planar trans-coordination geometry, while in the VOL2, the vanadium center has a distorted tetragonal pyramidal N2O3 coordination sphere. The HSA-binding was also determined, using fluorescence quenching, UV-vis spectroscopy, and circular dichroism (CD) titration method. The obtained results revealed that the HSA affinity for binding the synthesized compounds follows as PdL2>CuL2>VOL2>NiL2, indicating the effect of metal ion on binding constant. The distance between these compounds and HSA was obtained based on the Förster's theory of non-radiative energy transfer. Furthermore, computational methods including molecular docking and our Own N-layered Integrated molecular Orbital and molecular Mechanics (ONIOM) were carried out to investigate the HSA-binding of the compounds. Molecular docking calculation indicated the existence of hydrogen bond between amino acid residues of HSA and all synthesized compounds. The formation of the hydrogen bond in the HSA-compound systems leads to their stabilization. The ONIOM method was utilized in order to investigate HSA binding of compounds more precisely in which molecular mechanics method (UFF) and semi empirical method (PM6) were selected for the low layer and the high layer, respectively. The results show that the structural parameters of the compounds changed along with binding to HSA, indicating the strong interaction between the compounds and HSA. The value of binding constant depends on the extent of the resultant changes. This should be mentioned that both theoretical methods calculated the Kb values in the same sequence and are in a good agreement with the experimental data.