Synthesis, Crystallographic Features, and Urease Inhibition Performance of Aromatic Dicarboxylate Copper-Based Architectures

Abstract

A series of novel aromatic dicarboxylate copper complexes were designed and synthesized via hydrothermal and solvothermal methods, and their structural and biological properties were systematically investigated. Single-crystal X-ray diffraction revealed that the copper centers adopt either distorted octahedral or square planar geometries, with the ligands acting as bridging units to form one-, two-, or three-dimensional frameworks. Intermolecular interactions, including hydrogen bonding, π–π stacking, and van der Waals contacts, contribute to lattice stability and framework rigidity. Comprehensive structure-activity analysis demonstrated that the urease inhibitory performance of these complexes is strongly influenced by the electronic properties of the ligands, the accessibility of the copper centers, and the topology of the metal-organic frameworks. Complexes with electron-withdrawing substituents, partially exposed metal sites, and moderate structural flexibility exhibited the highest inhibitory potency. These findings highlight the importance of fine-tuning both ligand electronics and three-dimensional framework geometry in the rational design of metal-based enzyme inhibitors. This study provides valuable insights into the relationship between crystal structure and biological activity, offering guidance for the development of efficient urease inhibitors and other bioactive metal-organic materials.