Protein interactions and drug displacement studies of novel copper(II) and zinc(II) complexes of a dipyrazinylpyridine ligand

The binding of HSA with two new Cu(II) and Zn(II) complexes of a dipyrazinyl pyridine ligand has been studied, and their drug displacement activity has been investigated. [Display omitted] •Syntheses of novel copper and zinc complexes of a dipyrazinyl pyridine ligand and their characterization by 1H NMR, ESR, and HRMS.•The interaction of HSA with metal complexes has been studied.•A drug displacement study has been done using ibuprofen, warfarin, and bilirubin.•A theoretical analysis by DFT and molecular docking has been done. A one-pot method was employed for the preparation of zinc and copper complexes of 4-methoxyphenyl-2,6-di(pyrazine-2-yl)pyridine ligand (L). The complexes were designed to acknowledge their potential as selective binders with serum albumins. The reaction of the metal chlorides with an excess of ligand L yielded mononuclear [CuL2]Cl2 (1) and [ZnL2]Cl2 (2) complexes. 1H NMR, UV–Vis spectroscopy, ESR, HRMS, XRD, and elemental analysis were carried out to characterize the complexes. The interactions of the synthesized complexes with Human Serum Albumin (HSA) and their drug displacement properties using ibuprofen and warfarin were investigated with the help of spectroscopic as well as molecular modeling techniques. Complex 1 exhibited better binding capability, indicated by its binding constant value (31.2 × 104 M−1) towards HSA, than complex 2 (5.6 × 104 M−1), as depicted from UV–Visible and fluorescence spectroscopic studies. Moreover, the complexes showed better binding affinity towards HSA than the corresponding free ligand (0.2 × 104 M−1). The mechanism through which fluorescence quenching of HSA takes place (when metal complexes 1–2 were added to it) is static in nature. The Stern-Volmer (SV) equation was utilized to deduce the binding constants (Kb) through a fluorescence titration method. Moreover, structure optimization of the synthesized complexes and theoretical studies using density functional theory (DFT) has been carried out to determine the nature of the interaction of the complexes with the biomolecules.