Chelating Properties of N₆O-Donors Toward Cu(II) Ions: Speciation in Aqueous Environments and Catalytic Activity of the Dinuclear Complexes

Abstract

This study focuses on the use of three isostructural N6O donor ligands, specifically known to form complexes with copper ions, to chelate Cu(II) from aqueous solutions. The corresponding Cu(II) complexes feature a dinuclear copper core mimicking the active site of natural superoxide dismutase (SOD) enzymes while also creating a coordination environment favorable for catalase (CAT) activity, being thus appealing as catalytic antioxidant systems. Given the critical role of copper dysregulation in the pathophysiology of Alzheimer’s disease (AD), these complexes may help mitigate the harmful effects of free Cu(II) ions: the goal is to transform copper’s reactive oxygen species (ROS)-generating properties into beneficial ROS-scavenging action. This study investigates the speciation, chelating efficiency, and metal selectivity of these ligands, as well as the antioxidant activity of the resulting complexes under aqueous and physiologically relevant conditions. Additionally, the ligands, equipped with functional groups for attaching targeting moieties, are conjugated with a small peptide that may act as an anti-aggregating agent of β-amyloid peptides, aiming to develop a multifunctional therapeutic strategy against Alzheimer’s disease.

Keywords

• copper
• SOD activity
• catalase activity
• peroxidase activity
• ligands
• chelators