Synthesis, Crystal Structures, Molecular Docking, and Urease Inhibitory Activities of Transition‐Metal Complexes with a 1,2,4‐Triazolecarboxylic Acid Derived Ligand

Four novel complexes, [Cu( L ) 2 (NH 3 ) 2 (H 2 O) 2 ] ( 1 ), {[Cu( L ) 2 (H 2 O) 2 ] · 2H 2 O} n ( 2 ), {[Zn( L ) 2 (H 2 O) 2 ] · 2H 2 O} n ( 3 ), and {[Fe( L ) 2 (H 2 O) 2 ] · 2H 2 O} n ( 4 ) (H L = 2‐{[4‐amino‐3‐(pyridin‐4‐yl)‐4,5‐dihydro‐1 H ‐1,2,4‐triazol‐5‐yl]thio}acetic acid) were synthesized and characterized by single‐crystal X‐ray diffraction analysis. Complex 1 exhibited a mononuclear structure. Complexes 2 , 3 , and 4 featured 2D networks. The crystal structures were stabilized by intermolecular hydrogen bonds to generate 3D supramolecular frameworks. The inhibitory activity was tested in vitro against jack bean urease. Among the four complexes, the two Cu II complexes 1 and 2 exhibited better inhibitory activity than the positive reference acetohydroxamic acid, with IC 50 values of 4.052 and 6.868 μ M , respectively, whereas the Zn II and Fe II complexes showed no activity. To explore the mechanism of inhibition of the enzyme, kinetics studies were carried out; the results indicated that both the activated complexes 1 and 2 operated through a mixed‐competitive inhibitory mechanism. Molecular docking was used to insert the most active complex 1 into the crystal structure of jack bean urease at the active site to determine the probable mode of binding.