Copper(II) and zinc(II) complexes of dimeric 8-hydroxyquinoline ligands: Synthesis, metal speciation, and biological evaluation

Hydroxyquinolines have garnered considerable attention due to their biomedical potential, particularly their ability to coordinate metal ions, which significantly influences their biological activity. In this study, a series of 8-hydroxyquinoline dimeric derivatives was synthesized and compared to their monomeric counterparts. The metal-binding properties of these compounds with zinc(II) and copper(II) ions were investigated using ESI-MS spectrometry and UV–Vis spectroscopy. The results revealed that 8-hydroxyquinoline dimers form highly stable metal complexes. Biological studies have demonstrated that the functionalization of the 8-hydroxyquinoline scaffold modulates its activity: the introduction of amine chains in monomeric systems decreases the antiproliferative effects, both in the ligand and metal complexes. Notably, the dimer derivative linked via diaminoethane exhibited the most potent antiproliferative and antibacterial activities. In contrast, the introduction of a diaminodioxaoctane linker reduced toxicity in bacteria and cancer cells, highlighting its promise as a biologically compatible metal-chelating agent. This study compares the zinc(II) and copper(II) binding properties of 8-hydroxyquinoline dimers and monomers. The formation of stable complexes was confirmed by ESI-MS and UV–Vis spectroscopy. Biological assays revealed that scaffold modifications of 8-hydroxyquinoline influence biological activity. The diaminoethylene-linked dimer exhibited potent antiproliferative and antibacterial effects, whereas the diaminodioxaoctane derivative displayed reduced toxicity and improved biocompatibility. • New dimeric hydroxyquinoline derivatives form highly stable Cu II and Zn II complexes. • The functionalization of 8-hydroxyquinoline can efficiently modulate the toxicity. • Metal complexes of ethylenediamine dimer show the highest cytotoxic activity. • Dioxadiamino linker reduces antiproliferative and antibacterial activities. • Ligands show promise for metal-based therapies and chelation therapy.