Introduction of a Fluorescent Probe to Amyloid‐β to Reveal Kinetic Insights into Its Interactions with Copper(II)

The kinetics of the interactions between amyloid-β (Aβ) and metal ions are crucial to understanding the physiological and pathological roles of Aβ in the normal brain and in Alzheimer's disease. Using the quenching of a fluorescent probe by Cu(2+), the mechanism of Aβ/Cu(2+) interactions in physiologically relevant conditions has been elucidated. Cu(2+) binds to Aβ at a near diffusion-limited rate, initially forming component I. The switching between component I and II occurs on the second timescale, with a significant energy barrier. Component I is much more reactive towards Cu(2+) ligands and likely responsible for initial Aβ dimer formation. Clioquinol (CQ) is shown to sequester Cu(2+) more effectively than other tested ligands. These findings have implications for the potential roles of Aβ in regulating neurotransmission, and for the screening of small molecules targeting Aβ-metal interactions.