Synthesis, crystal structures, DFT studies, molecular docking and urease inhibition studies of three Ni(II) complexes with a sexidentate N2O4-donor bis-Schiff base ligand

Abstract

Three Ni(II) complexes with a sexidentate N₂O₄-donor bis-Schiff base ligand, namely Ni(C₃₆H₃₄N₂O₈)·2CH₃OH (1), Ni(C₂₈H₃₄N₂O₈S₂)·H₂O (2) and Ni(C₄₀H₃₆N₄O₈)·3CH₃OH (3) (C₃₆H₃₄N₂O₈=1,2-bis(2-methoxy-6-formylphenoxy)ethane-l-phenylalanine; C₂₈H₃₄N₂O₈S₂=1,2-bis(2-methoxy-6-formylphenoxy)ethane-l-methionine; C₄₀H₃₆N₄O₈=1,2-bis(2-methoxy-6-formylphenoxy)ethane-l-tryptophan) were synthesized and structurally characterized. Theoretical studies of the three complexes were carried out by density functional theory (DFT) Becke's three-parameter hybrid (B3LYP) method employing the 6-31G basis set. Moreover, the inhibitory activities were tested in vitro against jack bean urease. At the same time, molecular docking was investigated to determine the probable binding mode by inserting the complexes into the active site of jack bean urease. The experimental values and docking simulation exhibited that complex 3 showed strong inhibitory activity (IC₅₀=11.27±2.08μM) compared with the positive reference acetohydroxamic acid. Their structure-activity relationships were further discussed.

Keywords: DFT studies; Molecular docking; Ni(II) complexes; Urease inhibitors; X-ray structures.