cation–π interaction

It is easy to imagine a positive charge being attracted to a negative one. Less obvious is that a positive charge is also pulled toward the flat face of an aromatic ring like benzene. The reason is that the ring's cloud of π-electrons sits above and below its plane, giving each face a partial negative character that a cation finds attractive. This is the cation–π interaction.

It can be surprisingly strong — in some cases comparable to or stronger than a salt bridge — and it is highly directional, favoring the cation sitting right over the center of the ring face. Common players are a positively charged group on the ligand (an ammonium, guanidinium or metal-like center) meeting an aromatic side chain such as tryptophan, tyrosine or phenylalanine, or the reverse arrangement.

Cation–π interactions are central to recognition in many biological systems — neurotransmitter receptors that bind acetylcholine, for example, use an aromatic 'box' to cradle its positive trimethylammonium head. In drug design they offer a route to potency and selectivity that exploits charge without forming a full ionic contact, though, like other charged interactions, their strength is reduced by competing solvation in water.