Substituent effects in sandwich configurations of multiply substituted benzene dimers are not solely governed by electrostatic control.

Noncovalent interactions between pi systems are central to understanding protein folding and the stability of DNA. Considerable controversy exists about whether substituent effects in pi-pi interactions can be understood purely on the basis of electrostatic interactions or whether other effects must be included to understand observed trends. In this work, we show that in general, pi-pi interactions are not governed solely by electrostatic control. We do not observe a linear correlation between the relative interaction energies and the sums of Hammett parameters in the case of multiply substituted face-to-face benzene dimers. Instead, differential dispersion effects can be so large that even molecules with wildly different electrostatic potentials can exhibit similar attractions to benzene.