Stereochemistry of charged nitrogen-aromatic interactions and its involvement in ligand-receptor binding

Recently, new evidence was found for the involvement of charged nitrogen-aromatic interactions in ligand-receptor binding. In this study we report two favourable orientations of a phenyl ring with respect to a R-N+(CH3)3 group, based on crystal structure statistics from the Cambridge Structural Database. In the first orientation, the phenyl ring is situated in between the substituents at about 4.5 A from the nitrogen atom, and the ring is approximately oriented on the sphere around the nitrogen atom. In the second orientation, the phenyl ring is situated in the same direction as one of the N-C bonds at about 6.0 A from the nitrogen atom, and the ring is tilted with respect to the sphere around the nitrogen atom. The same two orientations were also found in the crystal structures of three ligand-receptor complexes, which implies that these orientations probably play a major role in molecular recognition mechanisms.