Copper(I) Chelators for Alzheimer's Disease

A component of the neurotoxicity of the beta amyloid peptide (Aβ) of Alzheimer's disease is its ability to generate superoxide, hydrogen peroxide, and hydroxyl radicals by reaction of its reduced copper complex Aβ/Cu⁺ with molecular oxygen. The objective of the present work was to devise compounds, L, that could remove Cu⁺ from Aβ/Cu⁺, with the property that L/Cu⁺ itself would not be capable of reducing O₂ or hydrogen peroxide. We show by density functional calculations that several pincer-type compounds with two imidazole rings and a sulfur or nitrogen have the desired combination of Cu⁺ binding affinity and Cu²⁺ reduction potential.