Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published November 21, 2015 | Published + Supplemental Material + Accepted Version
Journal Article Open

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


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 NH_4+ and NMe_4+ 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.

Additional Information

© 2015 the Owner Societies. Received 6th August 2015; Accepted 8th October 2015; First published online 08 Oct 2015. We thank the NIH (NS 34407) for support of this work.

Attached Files

Published - c5cp04668h.pdf

Accepted Version - nihms731164.pdf

Supplemental Material - c5cp04668h1.pdf


Files (11.8 MB)
Name Size Download all
2.0 MB Preview Download
7.9 MB Preview Download
1.8 MB Preview Download

Additional details

August 20, 2023
October 25, 2023