Issue 20, 2015

Coordination properties of a metal chelator clioquinol to Zn2+ studied by static DFT and ab initio molecular dynamics

Abstract

Several lines of evidence supporting the role of metal ions in amyloid aggregation, one of the hallmarks of Alzheimer's disease (AD), have turned metal ion chelation into a promising therapeutic treatment. The design of efficient chelating ligands requires proper knowledge of the electronic and molecular structure of the complexes formed, including their hydration properties. Among various potential chelators, clioquinol (5-chloro-7-iodo-8-hydroxyquinoline, CQH) has been evaluated with relative success in in vitro experiments and even in phase 2 clinical trials. Clioquinol interacts with Zn(II) to lead to a binary metal/ligand 1 : 2 stoichiometric complex in which the phenolic group of CQH is deprotonated, resulting in Zn(CQ)2 neutral complexes, to which additional water molecules may coordinate. In the present work, the coordinative properties of clioquinol in aqueous solution have been analyzed by means of static, minimal cluster based DFT calculations and explicit solvent ab initio molecular dynamics simulations. Results from static calculations accounting for solvent effects by means of polarized continuum models suggest that the preferred metal coordination environment is tetrahedral Zn(CQ)2, whereas ab initio molecular dynamics simulations point to quasi degenerate penta Zn(CQ)2(H2O) and hexa Zn(CQ)2(H2O)2 coordinated complexes. The possible reasons for these discrepant results are discussed.

Graphical abstract: Coordination properties of a metal chelator clioquinol to Zn2+ studied by static DFT and ab initio molecular dynamics

Supplementary files

Article information

Article type
Paper
Submitted
19 Mar 2015
Accepted
23 Apr 2015
First published
23 Apr 2015

Phys. Chem. Chem. Phys., 2015,17, 13582-13589

Author version available

Coordination properties of a metal chelator clioquinol to Zn2+ studied by static DFT and ab initio molecular dynamics

L. Rodríguez-Santiago, J. Alí-Torres, P. Vidossich and M. Sodupe, Phys. Chem. Chem. Phys., 2015, 17, 13582 DOI: 10.1039/C5CP01615K

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements