Structural Modulation and Bioactivity Assessment of Mixed-Ligand Copper Complexes Targeting Urease
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Abstract
Mixed-ligand copper complexes have emerged as promising candidates for enzyme inhibition due to their versatile coordination chemistry and tunable biological activity. In this study, a series of mixed-ligand copper complexes were designed and synthesized with structural modifications aimed at enhancing urease inhibitory activity. The complexes were comprehensively characterized using NMR, IR, UV-Vis spectroscopy, mass spectrometry, and X-ray crystallography where feasible, confirming successful coordination and revealing variations in coordination geometry. Urease inhibition assays demonstrated that ligand structure significantly influenced biological activity, with electron-donating and sterically accessible ligands exhibiting higher potency. Kinetic studies indicated competitive or mixed-type inhibition, while molecular docking simulations supported these findings by showing favorable interactions with key residues in the urease active site. Structure-activity relationship analysis highlighted the critical roles of electronic properties, steric effects, and coordination geometry in modulating enzyme inhibition. The results provide valuable insights into rational ligand design for copper-based metalloenzyme inhibitors and establish mixed-ligand copper complexes as potential candidates for therapeutic applications targeting urease-related pathologies.
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