Urease inhibition studies of two Cu(II) complexes with an ONO tridentate Schiff base and two different secondary ligands: An experimental, DFT, molecular docking and molecular dynamics study

Abstract

Two mononuclear Copper(II) complexes, identified as [Cu(C10H8NO4F)(C6H7N)] (C1) and [Cu(C10H8NO4F)(C12H8N2)]·H2O·CH3OH (C2), incorporating a tridentate Schiff-base ligand with an ONO coordination (C10H8NO4F = 5-fluoro-2-hydroxybenzylidene-L‑serine) and two unique auxiliary ligands (C6H7N = 4-methylpyridine and C12H8N2 = 1,10-phenanthroline) were developed and detailed structurally. Density functional theory (DFT) evaluations of these complexes employed Becke's three-parameter hybrid (B3LYP) approach within the Gaussian 16 computational package. The outcomes from computational analysis corresponded with experimental data. Additionally, the inhibition capabilities of complexes C1 and C2 were evaluated in vitro targeting jack bean urease. Simultaneously, molecular docking was utilized to determine potential binding interactions. Experimental results and docking analyses showed that C1 had considerable inhibitory strength (IC50 = 2.44 ± 0.15 μM) relative to the benchmark control, acetohydroxamic acid (IC50 = 27.73 ± 2.93 μM). Furthermore, a 100-ns molecular dynamics assessment was performed to examine the interaction stability of urease with C1 and C2, using the Desmond 2021 tool from Schrödinger. The correlation between structural configurations and inhibition efficacy was further explored through molecular docking, density functional theory analysis, and molecular dynamics evaluations.