Details

Autor(en) / Beteiligte

• Nguyen, Michel
• Vendier, Laure
• Stigliani, Jean‐Luc
• Meunier, Bernard
• Robert, Anne

Titel

Structures of the Copper and Zinc Complexes of PBT2, a Chelating Agent Evaluated as Potential Drug for Neurodegenerative Diseases

Ist Teil von

• European journal of inorganic chemistry, 2017-01, Vol.2017 (3), p.600-608

Ort / Verlag

Weinheim: Wiley Subscription Services, Inc

Erscheinungsjahr

2017

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Clioquinol and PBT2, based on a 8‐hydroxyquinoline scaffold, have been proposed as drugs able to treat the disruption of metal homeostasis in neurodegenerative diseases, especially Alzheimer's disease (AD). They are believed to reduce metal–amyloid (Aβ) interactions and regulate redox homeostasis in AD brains. Therefore, the understanding of the molecular aspects of metal chelation by 8‐hydroxyquinolines is clearly important for the development of future metal chelators as putative drugs. Despite this, literature data on these aspects are rather limited. We report herein the stoichiometries and structures of the copper(II) and zinc(II) complexes of PBT2. The reported data indicate that the coordination chemistry of PBT2 is characterized by high versatility and a lack of metal selectivity. For each metal, several complexes can co‐exist, and the copper complexes differ from their zinc analogues. The structures of the PBT2 complexes are significantly different to those reported for complexes of clioquinol, the prototype of this series. As PBT2 can be a bi‐ or tridentate ligand, different complexes can be formed with copper, including ternary complexes PBT2–Cu–X. The versatile structures of the metal complexes of PBT2 in vivo, especially in the brains of AD patients, should be dependent on competitive ligands, including amyloids. This feature might be a limitation for an efficient extraction of copper from amyloids. The coordination of CuII and ZnII by PBT2, an 8‐hydroxyquinoline derivative proposed to regulate copper homeostasis in Alzheimer's disease, is very versatile. The ability of PBT2 to form 2:1 complexes with CuII may lessen the potential of 8‐hydroxyquinolines as future metal‐chelating drugs. Tetradentate chelating ligands should be preferred.