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 spectrophotometry. 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 ligands and their 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.