Urease inhibition studies of six Ni(II), Co(II) and Cu(II) complexes with two sexidentate N2O4-donor bis-Schiff base ligands: An experimental and DFT computational study.

Six novel complexes, [Ni(C₃₆H₃₄N₂O₁₀)]·2.25CH₃OH·0.5C₄H₁₀O (1), [Co(C₃₆H₃₄N₂O₁₀)] (2), [Cu(C₃₆H₃₄N₂O₁₀)]·2CH₃OH (3), [Ni(C₃₆H₃₂N₂O₈Cl₂)]·2CH₃OH (4), [Co(C₃₆H₃₂N₂O₈Cl₂)]·4CH₃OH (5) and [Cu(C₃₆H₃₂N₂O₈Cl₂)]·2CH₃OH (6) with two sexidentate N₂O₄-donor bis-Schiff base ligands (C₃₆H₃₄N₂O₁₀ = 1,2-bis(2-methoxy-6-formylphenoxy)ethane-l-tyrosine; C₃₆H₃₂N₂O₈Cl₂ = 1,2-bis(2-methoxy-6-formylphenoxy)ethane-l-4-chlorophenylalanine) have been synthesized and structurally characterized. Theoretical calculation of the six complexes was carried out by density functional theory (DFT) Becke's three-parameter hybrid (B3LYP) method employing the 6-3lG basis set, indicating that the calculation results are in accordance with experimental results. Moreover, the inhibitory activities of complexes 1-6 were tested in vitro against jack bean urease. At the same time, molecular docking was investigated to determine the probable binding mode. The experimental values and docking simulation exhibited that complexes 3 and 6 showed strong inhibitory activity (IC₅₀ = 10.36 ± 1.13, 15.63 ± 3.04 μM) compared with the positive reference acetohydroxamic acid (IC₅₀ = 26.99 ± 1.43 μM). Their structure-inhibitory activity relationship was further discussed from the perspective of molecular docking and theoretical calculation.