Cu(I) chelators: Useful tools to reveal and control Cu(I) homeostasis and toxicity

Copper (Cu) is an essential trace element for numerous biological processes, including energy production, aerobic respiration, and antioxidant defense. Despite its importance, disruptions in Cu homeostasis can lead to severe pathological conditions, such as Wilson's disease (WD), Menkes disease (MD), Alzheimer's disease (AD), and cancer. The present review focuses on the role of Cu(I) probes and chelators as molecular tools for understanding and managing copper-related toxicity and misregulation. It provides an overview of Cu(I) coordination chemistry, trafficking pathways, and the dual toxicity mechanisms of Cu (both ROS-dependent and ROS-independent). Key experimental approaches to study Cu(I), including chromophoric and fluorescent probes, are highlighted, with a focus on their design, applications, and limitations. Finally, the therapeutic potential of Cu(I)-targeting ligands is discussed, showcasing their role in fighting oxidative stress and restoring metal homeostasis in diseases. Hence, this review offers a comprehensive perspective on Cu(I) chelation's role in advancing both fundamental understanding and therapeutic strategies against copper-related disorders.