The effects of substituents on the geometry of π-π interactions

We have designed and utilized a simple molecular recognition system to study the substituent effects in aromatic interactions. Recently, we showed that 3- and 3,5-disubstituted benzoyl leucine diethyl amides with aromatic rings of varying electronic character organized into homochiral dimers in the solid state through a parallel displaced π-π interaction and two hydrogen bonds, but no such homochiral dimerization was observed for the unsubstituted case. This phenomenon supports the hypothesis that substituents stabilize π-π interactions regardless of their electronic character. To further investigate the origin of substituent effects for π-π interactions, we synthesized and crystallized a series of 4-substituted benzoyl leucine diethyl amides. Surprisingly, only two of the 4-substituted compounds formed homochiral dimers. A comparison among the 4-substituted compounds that crystallized as homochiral dimers and their 3-substituted counterparts revealed that there are differences in regard to the geometry of the aromatic rings with respect to each other, which depend on the electronic nature and location of the substituent. The crystal structures of the homochiral dimers that showed evidence of direct, local interactions between the substituents on the aromatic rings also displayed nonequivalent dihedral angles in the individual monomers. The crystallographic data suggests that such "flexing" may be the result of the individual molecules orienting themselves to maximize the local dipole interactions on the respective aromatic rings. The results presented here can potentially have broad applicability towards the development of molecular recognition systems that involve aromatic interactions.