Experimental and computational studies on two Cu(Ⅱ) Schiff base complexes: crystal structure, DFT, urease inhibitory activity, molecular docking, molecular dynamics and ADME study

In the present study, two Cu(II) complexes incorporating a Schiff base ligand, termed CuSBCs, were synthesized and subjected to structural characterization. The complexes are denoted as [Cu(C 10 H 8 NO 4 F)(C 10 H 9 N 3 )]·H 2 O ( C1 ) and [Cu(C 10 H 8 NO 4 F)(C 12 H 12 N 2 )]·H 2 O·CH 3 OH ( C2 ), featuring the Schiff base ligand (SBL, C 10 H 8 NO 4 F) and distinct auxiliary ligands, specifically 2,2’-dipyridylamine and 5,5’-dimethyl-2,2’-bipyridine. Within these two complexes, the central Cu(II) ion exhibits pentacoordination, binding to ONO donor sites of the SBL as well as two nitrogen donor atoms provided by the auxiliary ligand, yielding a distorted square pyramidal geometry. Theoretical computations for both complexes were performed using density functional theory (DFT) with the B3LYP functional via the Gaussian 16 program. The computational results are in good agreement with experimental observations. Notably, both complexes exhibited significant inhibitory activity against jack bean urease (UA), with C1 (IC 50 = 4.79 ± 0.77 µM) outperforming C2 (IC 50 = 6.83 ± 1.19 µM) and the reference inhibitor acetohydroxamic acid (AHA). Molecular docking (MOD) and molecular dynamics (MD) simulations reveal that the superior activity of C1 originates from its better steric matching and more stable interactions with the enzyme active site, providing structural evidence for the experimental activity trend. In addition, ADME predictions indicated that both complexes possess favorable drug-like properties and promising bioavailability. These findings highlight the promising therapeutic potential of Cu(Ⅱ) Schiff base complexes as UA inhibitors.