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J Inorg Biochem. 2014 Apr;133:50-6. doi: 10.1016/j.jinorgbio.2014.01.003. Epub 2014 Jan 16.

The solution structure of the copper clioquinol complex.

Author information

1
Molecular and Environmental Sciences Research Group, Department of Geological Sciences, University of Saskatchewan, SK S7N 5E2, Canada.
2
Molecular and Environmental Sciences Research Group, Department of Geological Sciences, University of Saskatchewan, SK S7N 5E2, Canada; Department of Chemistry, University of Saskatchewan, SK S7N 5C9, Canada.
3
Molecular and Environmental Sciences Research Group, Department of Geological Sciences, University of Saskatchewan, SK S7N 5E2, Canada; Canadian Light Source Inc., Saskatoon, SK S7N 2V3, Canada.
4
Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
5
Molecular and Environmental Sciences Research Group, Department of Geological Sciences, University of Saskatchewan, SK S7N 5E2, Canada; Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada.
6
Molecular and Environmental Sciences Research Group, Department of Geological Sciences, University of Saskatchewan, SK S7N 5E2, Canada; Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada. Electronic address: g.george@usask.ca.

Abstract

Clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) recently has shown promising results in the treatment of Alzheimer's disease and in cancer therapy, both of which also are thought to be due to clioquinol's ability as a lipophilic copper chelator. Previously, clioquinol was used as an anti-fungal and anti-protozoal drug that was responsible for an epidemic of subacute myelo-optic neuropathy (SMON) in Japan during the 1960s, probably a myeloneuropathy arising from a clioquinol-induced copper deficiency. Previous X-ray absorption spectroscopy of solutions of copper chelates of clioquinol suggested unusual coordination chemistry. Here we use a combination of electron paramagnetic, UV-visible and X-ray absorption spectroscopies to provide clarification of the chelation chemistry between clioquinol and copper. We find that the solution structures for the copper complexes formed with stoichiometric and excess clioquinol are conventional 8-hydroxyquinolate chelates. Thus, the promise of clioquinol in new treatments for Alzheimer's disease and in cancer therapy is not likely to be due to any novel chelation chemistry, but rather due to other factors including the high lipophilicity of the free ligand and chelate complexes.

KEYWORDS:

Clioquinol; Copper chelation; Density functional theory; X-ray absorption spectroscopy

PMID:
24503514
DOI:
10.1016/j.jinorgbio.2014.01.003
[Indexed for MEDLINE]
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