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Superoxide Reduction by Cu‐Amyloid Beta Peptide Complexes: A Density Functional Theory Study
Author(s) -
Arrigoni Federica,
Di Carlo Chiara,
Rovetta Alberto,
De Gioia Luca,
Zampella Giuseppe,
Bertini Luca
Publication year - 2022
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.202200245
Subject(s) - chemistry , superoxide , radical , reactive oxygen species , oxidative stress , density functional theory , peroxide , peptide , amyloid beta , copper , oxygen , computational chemistry , biochemistry , organic chemistry , enzyme
Oxidative stress and copper dyshomeostasis are well established factors in the course of Alzheimer's disease (AD). Indeed, the pathological interaction of copper with the amyloid peptide is able to induce reactive oxygen species (ROS) production through a three‐step cycle in which O 2 is gradually reduced to superoxide, oxygen peroxide and finally to highly neurotoxic OH⋅ radicals. The purpose of this study has been to investigate at a computational level, by Density Functional Theory (DFT) and molecular mechanics techniques, the final two steps of O 2 reduction to OH − +OH radical i.e the superoxide and hydroperoxide reduction by ascorbate, on different Cu(II) ⋅ Aβ coordination models. At variance with the first step of O 2 reduction to O 2 .− characterized by high energy barrier, the successive O 2 .− and O 2 H − reductions are low energy barriers processes and that the OH⋅ radical formation is further favored by the possibility of Cu(II) ⋅ Aβ to form the Asp1 amino terminal radical. We discuss the results obtained from the perspective of the recent findings in the Aβ redox chemistry in AD pathology.