Cation–π interactions in ligand recognition and catalysis

The cation–π interaction is a potent, general noncovalent binding force that is observed in a wide range of biological contexts. Here, we present an overview of well documented cases in which a cation–π interaction makes an important contribution to small-molecule recognition at a protein binding site. From these and other studies it is clear that, in addition to the hydrophobic effect, hydrogen bonding and ion pairing, the cation–π interaction must be considered when evaluating drug-receptor interactions.