Cation- interaction is a noncovalent molecular interaction between the face of an electron-rich system (e.g. benzene, ethylene) with an adjacent cation (e.g. Li+, Na+). This unusual interaction is an example of noncovalent bonding between a monopole (cation) and a quadrupole ( system). Cation- interaction energies are of the same order of magnitude as hydrogen bonds or salt bridges and play an important role in molecular recognition.
Origin of the Effect
, the model
system has no permanent dipole moment
, as the contributions of the weakly polar carbon-hydrogen bonds cancel due to molecular symmetry
. However, the electron-rich
system above and below the benzene ring hosts a partial negative charge. In order to counterbalance this sandwiching negative charge, a positive charge is associated within the plane in which all benzene atoms lie. An (electric) quadrupole
(a pair of dipoles, which do not cancel each other) results. The negatively charged
system can then interact favorably with positively charged ions.
Influences on the Strength of the Cation- Interaction
interaction is comparable in strength to hydrogen bonding and can in some cases be a decisive intermolecular force
. Several criteria influence the strength of the bonding: the nature of the cation, the subsitutents
system, as well as the solvent.
Nature of the Cation
), smaller and more positively charged cations lead to larger electrostatic attraction. The following table shows a series of Gibbs free energy
changes for the interaction of benzene with several alkaline metals
in the gas phase. The influence of the ionic radius
, is evident.
|| Rb+ |
| -G [kcal/mol]
|| 16 |
|| 152 |
Substituents on system
The electronic properties of the substituents
system also have an influence on the strength of the attraction. Electron withdrawing groups
(e. g. Cyano
-CN) decrease the amount of negative charge in the
system and thus weaken the interaction. On the contrary, electron donating substituents
(e.g. amino –NH2
) increase the charge separation of the quadrupole and strengthen the cation-
binding. This relationship is illustrated quantitatively in the margin for several substituents.
Influence of the solvent
Additionally, the nature of the solvent also determines the relative strength of the bonding. Most data on cation-
interaction is acquired in the gas phase, as the attraction is most pronounced in that case. Any intermediating solvent molecule will attenuate the effect, which is why it becomes less pronounced with increasing solvent polarity
Cation- Interaction in Nature
Nature’s building blocks consist of aromatic moieties, too. Amino acid
side chains of tryptophane
or the DNA bases
are capable of binding to cationic species (not only metal ions, but also charged amino acid side chains, ...). Therefore, cation-
interactions can play an important role in stabilizing the three dimensional structure of a protein
. A very impressive example is given by the nicotinamide acetylcholine receptor
whose molecular recognition mechanism of its substrate acetylcholine
(a positively charged molecule) nearly entirely bases on cation-
In many respects, anion
interaction is opposite to cation-
interaction, although the underlying principles are identical. Significantly less examples are known to date. In order to attract a negative charge, the charge distribution of the
system has to be reversed. This is achieved by placing several strong electron withdrawing substituents
system (e. g.
hexafluorobenzene). The anion-
effect is advantageously exploited in chemical sensors for specific anions.
- J. C. Ma, and D. A. Dougherty (1997). "The Cation-π Interaction". Chem. Rev. 97 (5): 1303. .