DFT studies on redox properties of copper-chelating cuprizone: Unusually high-valent copper(III) state

We investigated the structures and redox properties of copper-chelating cuprizone using DFT-B3LYP calculations to gain insights into its toxicity causing neurodegeneration similar to lesions in prion diseases. We found that the copper-cuprizone complex has redox potentials of the Cu(III)/Cu(II) couple that range from −0.05 to +0.98 V (vs. normal hydrogen electrode), which are low enough to stabilize tri-valent copper(III) states. The resulting unusually high-valent copper(III) can be involved in cytotoxiciy to disrupt copper metabolism and/or to cause oxidative stress. This study on the redox behavior of copper-chelating cuprizone may provide not only an insight into its copper(III)-mediated toxicity but also a key to understanding for the pathogenesis of prion diseases.