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

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.