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Preparation and Study of New Poly‐8‐Hydroxyquinoline Chelators for an anti‐Alzheimer Strategy
Author(s) -
Deraeve Céline,
Boldron Christophe,
Maraval Alexandrine,
Mazarguil Honoré,
Gornitzka Heinz,
Vendier Laure,
Pitié Marguerite,
Meunier Bernard
Publication year - 2008
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.200701024
Subject(s) - 8 hydroxyquinoline , chemistry , chelation , ligand (biochemistry) , monomer , metal , linker , copper , quinoline , covalent bond , metal ions in aqueous solution , heteroatom , crystallography , stereochemistry , inorganic chemistry , organic chemistry , receptor , polymer , ring (chemistry) , biochemistry , computer science , operating system
Abstract Fourteen different ligands have been synthesized with two covalently linked 8‐hydroxyquinoline motifs that favor metal complexation. These bis‐chelators include different bridges at the C2 positions and different substituents to modulate their physicochemical properties. They can form metal complexes in a ratio of one ligand per metal ion with Cu II and Zn II , two metal ions involved in the formation of amyloid aggregates of the toxic Aβ‐peptides in the Alzheimer disease. The apparent affinity of all bis‐8‐hydroxyquinoline ligands for Cu II and Zn II are similar with log K Cu II≈16 and log K Zn II≈13 and are 10 000 times more efficient than for the corresponding 8‐hydroxyquinoline monomers. Their strong chelating capacities allow them to inhibit more efficiently than the corresponding monomers the precipitation of Aβ‐peptides induced by Cu II and Zn II and also to inhibit the toxic formation of H 2 O 2 due to copper complexes of Aβ. The best results were obtained with a one‐atom linker between the two quinoline units. X‐ray analyses of single‐crystals of Cu II , Zn II or Ni II complexes of 2,2′‐(2,2‐propanediyl)‐bis(8‐hydroxyquinoline), including a one‐atom linker, showed that all heteroatoms of the bis‐8‐hydroxyquinoline ligand chelate the same metal ion in a distorted square‐planar geometry. The Cu II and Zn II complexes include a fifth axial ligand and are pentacoordinated.