Fabrication of Substituent-Regulated Two-Dimensional Copper-Based Coordination Polymers as Urease Inhibitors

Abstract

This article reports the design and synthesis of two copper-based coordination polymers (Cu-CPs) constructed from mixed ligands containing a bis-pyridine-bis-amide group and trimellitic acid. By using substituent-regulated acids, the simplified two-dimensional (2D) double layers for the Cu-CP-1 and Cu-CP-2 possess different grid windows, which can be served as a kind of urease inhibitors (UIs) and their inhibition mechanisms were explored in details. The results show that both Cu-CPs exhibited good urease inhibitory activity, and the inhibitory activities of all derivatives were higher than that of the standard thio urea, with UI-2 exhibiting better urease inhibitory performance. To better understand the potential mechanism of urease inhibition by these CPs, enzyme kinetics analysis was performed using Lineweaver− Burk (L−B) plots at different inhibitor concentrations, which indicated that UI-1 and UI-2 exhibited noncompetitive inhibitory nature. Additionally, molecular docking confirmed the binding interactions of UI-1 and UI-2 with the active site of urease. The urease inhibition experiments were successfully verified, and the effects of the structures of CPs on urease inhibition were measured through DFT calculations.