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N 4 ‐Tetradentate Chelators Efficiently Regulate Copper Homeostasis and Prevent ROS Production Induced by Copper‐Amyloid‐β 1–16
Author(s) -
Zhang Weixin,
Liu Yan,
Hureau Christelle,
Robert Anne,
Meunier Bernard
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201801387
Subject(s) - copper , oxidative stress , zinc , chemistry , homeostasis , selectivity , chelation , metal , oxidative phosphorylation , in vitro , biophysics , biochemistry , inorganic chemistry , microbiology and biotechnology , biology , organic chemistry , catalysis
The disruption of copper homeostasis and the oxidative stress induced by Cu‐amyloids are crucial features of Alzheimer's disease pathology. The copper specific N 4 ‐tetradendate ligands TDMQ20 and 1 are able to fully inhibit in vitro the aerobic oxidation of ascorbate induced by Cu‐Aβ 1‐16 , even in the presence of 100 molar equivalents of Zn II with respect to Cu II , whereas other ligands with N 2 O 2 or N 3 O 2 coordination spheres failed to do so. This essential result indicates that, in addition to metal selectivity, the coordination sphere of copper chelators should exhibit a N 4 ‐tetradendate motif to be able to reduce an oxidative stress in the zinc‐rich physiological environment of brain. The N 4 ‐scaffolds of these two aminoquinoline‐based ligands, TDMQ20 or 1 , suitable for a square‐planar coordination of copper(II), allowed them to enhance both the selectivity for copper and the ability to reduce the oxidative stress induced by copper‐amyloid in a zinc‐rich environment.