A multifaceted study of three Cu(II) Schiff base complexes as urease inhibitors: Derived from experimental and computational approaches

Herein, we explore the development of three copper(II) Schiff base complexes (Cu-SBC, C1 - C3 ) aimed at inhibiting urease (UA), achieved through the thoughtful design of ligands. By integrating a fluorinated Schiff base ligand (SBL) with auxiliary ligands—namely, 2-methylimidazole, 2-ethylimidazole, and 6,6′-dimethyl-2,2′-bipyridine—this research systematically examines the impact of steric factors on the inhibition of the UA enzyme. The synthesized complexes underwent comprehensive characterization, including crystallographic analysis. The three synthesized Cu(II) complexes exhibit two distinct coordination geometries dictated by their auxiliary ligands. C1 and C2 display four-coordinate distorted square planar geometries, while C3 adopts a five-coordinate distorted square pyramidal configuration. The biological evaluation revealed that C1 demonstrated a markedly enhanced UA inhibitory activity compared to the standard reference acetohydroxamic acid (IC 50 : 6.12 ± 0.44 vs. 27.73 ± 2.93 μM). Computational methodologies were employed to complement the experimental investigations, elucidating the molecular underpinnings of the observed activity disparities among the complexes. Consequently, the structure-activity relationship analysis indicates that steric hindrance is crucial in modulating the UA inhibitory activity, providing important perspectives for the development of new UA inhibitors and their potential uses in biomedicine.