Cation–π interaction

Cation–π interaction is a noncovalent molecular interaction between the face of an electron-rich π system (e.g. benzene, ethylene, acetylene) and an adjacent cation (e.g. Li+, Na+). This interaction is an example of noncovalent bonding between a monopole (cation) and a quadrupole (π system). Bonding energies are significant, with solution-phase values falling within the same order of magnitude as hydrogen bonds and salt bridges. Similar to these other non-covalent bonds, cation–π interactions play an important role in nature, particularly in protein structure, molecular recognition and enzyme catalysis. The effect has also been observed and put to use in synthetic systems. Benzene, the model π 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 π system above and below the benzene ring hosts a partial negative charge. A counterbalancing positive charge is associated with the plane of the benzene atoms, resulting in an electric quadrupole (a pair of dipoles, aligned like a parallelogram so there is no net molecular dipole moment). The negatively charged region of the quadrupole can then interact favorably with positively charged species; a particularly strong effect is observed with cations of high charge density. The most studied cation–π interactions involve binding between an aromatic π system and an alkali metal or nitrogenous cation. The optimal interaction geometry places the cation in van der Waals contact with the aromatic ring, centered on top of the π face along the 6-fold axis. Studies have shown that electrostatics dominate interactions in simple systems, and relative binding energies correlate well with electrostatic potential energy. The Electrostatic Model developed by Dougherty and coworkers describes trends in binding energy based on differences in electrostatic attraction.