Chasing the Elusive “In‐Between” State of the Copper‐Amyloid β Complex by X‐ray Absorption through Partial Thermal Relaxation after Photoreduction

Abstract

The redox activity of Cu ions bound to the amyloid‐β (Aβ) peptide is implicated as a source of oxidative stress in the context of Alzheimer's disease. In order to explain the efficient redox cycling between CuII‐Aβ (distorted square‐pyramidal) and CuI‐Aβ (digonal) resting states, the existence of a low‐populated “in‐between” state, prone to bind Cu in both oxidation states, has been postulated. Here, we exploited the partial X‐ray induced photoreduction at 10 K, followed by a thermal relaxation at 200 K, to trap and characterize by X‐ray Absorption Spectroscopy (XAS) a partially reduced Cu‐Aβ1–16 species different from the resting states. Remarkably, the XAS spectrum is well‐fitted by a previously proposed model of the “in‐between” state, hence providing the first direct spectroscopic characterization of an intermediate state. The present approach could be used to explore and identify the catalytic intermediates of other relevant metal complexes.