Design and Synthesis of Novel Copper-Based Coordination Polymers with Enhanced Urease Inhibition Activity

Abstract

Urease is a key metalloenzyme involved in biological, agricultural, and environmental processes, and its excessive activity can lead to pathogenic infections, nitrogen loss, and environmental pollution. Developing efficient, stable, and controllable urease inhibitors is therefore of considerable significance. In this study, we report the rational design and theoretical framework for novel two-dimensional copper-based coordination polymers (Cu-CPs) regulated by tridentate auxiliary ligands. The integration of multidentate ligands, optimized copper coordination geometries, and tailored polymer architectures enables spatial and electronic complementarity with urease active sites, enhancing inhibitory efficiency. Computational modeling and crystal structure prediction reveal that multinuclear copper centers and functionalized ligands synergistically improve binding and prolong inhibition. The synthetic strategies, including solution-based synthesis, self-assembly, and stepwise assembly, yield highly crystalline and thermally stable polymers, while adhering to principles of green chemistry. The proposed inhibition mechanisms involve direct coordination with the enzyme, steric hindrance, and multivalent effects. These Cu-CPs demonstrate potential applications in medical treatment of urease-producing pathogens, improved nitrogen fertilizer utilization, and environmental nitrogen management. Future work may explore multifetal synergistic designs, high-throughput computational screening, and biocompatibility optimization to develop efficient, selective, and sustainable urease inhibitors.