Issue 43, 2015

Cation–π interactions: computational analyses of the aromatic box motif and the fluorination strategy for experimental evaluation

Abstract

Cation–π interactions are common in biological systems, and many structural studies have revealed the aromatic box as a common motif. With the aim of understanding the nature of the aromatic box, several computational methods were evaluated for their ability to reproduce experimental cation–π binding energies. We find the DFT method M06 with the 6-31G(d,p) basis set performs best of several methods tested. The binding of benzene to a number of different cations (sodium, potassium, ammonium, tetramethylammonium, and guanidinium) was studied. In addition, the binding of the organic cations NH4+ and NMe4+ to ab initio generated aromatic boxes as well as examples of aromatic boxes from protein crystal structures were investigated. These data, along with a study of the distance dependence of the cation–π interaction, indicate that multiple aromatic residues can meaningfully contribute to cation binding, even with displacements of more than an angstrom from the optimal cation–π interaction. Progressive fluorination of benzene and indole was studied as well, and binding energies obtained were used to reaffirm the validity of the “fluorination strategy” to study cation–π interactions in vivo.

Graphical abstract: Cation–π interactions: computational analyses of the aromatic box motif and the fluorination strategy for experimental evaluation

Supplementary files

Article information

Article type
Paper
Submitted
06 Aug 2015
Accepted
08 Oct 2015
First published
08 Oct 2015
This article is Open Access
Creative Commons BY-NC license

Phys. Chem. Chem. Phys., 2015,17, 29262-29270

Author version available

Cation–π interactions: computational analyses of the aromatic box motif and the fluorination strategy for experimental evaluation

M. R. Davis and D. A. Dougherty, Phys. Chem. Chem. Phys., 2015, 17, 29262 DOI: 10.1039/C5CP04668H

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, 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 commercial 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