Interaction of a novel inorganic nickel complex with tyrosinase as potential inhibitor: Synthesis, spectroscopic, DFT, NBO, docking and ADMET properties

Abstract

The obtained Ni(II) complex has been synthesized and characterized by elemental analysis (EA), spectroscopic studies such as FT-IR, UV-Vis. and MS. Also, thermal analysis (TG and DTG) analysis, X-ray powder diffractometry (PXRD) and morphological (SEM/EDXS) measurements were as well performed. By using cyclic voltammetry (CV), the redox properties of NiII(L)2 complex was found to be a quasi-reversible Ni(II)/Ni(I) redox system. The structure of NiII(L)2 complex was investigated by utilizing density functional theory (DFT) calculations with the Becke 3-Lee-Yang-Parr (B3LYP) method employing the LANL2DZ basis set. Frontier molecular orbitals (FMOs), important parameters of reactivity, Mulliken charge and Natural bond orbitals (NBOs) computational studies on NiII(L)2 complex were carried out in the ground state using DFT theory at B3LYP/ LANL2DZ level. This complex was found to exhibit, in vitro, a strong tyrosinase inhibitory activity with an IC50 value of 5.7 μM approximately 6.5-fold better than kojic acid as positive control IC50 = 37.86 µM). The binding energy of the best pose, in silico, is – 8.7 kcal/mol. Thus, these results showed a good agreement with the experimental data obtained from the enzyme-inhibiting assay.