The conventional understanding of pi stacking involves quadrupole interactions between delocalized electrons in p-orbitals. In other words, aromaticity should be required for this interaction to occur. However, several groups have provided contrary evidence, calling into question whether pi stacking is a unique phenomenon or whether it extends to other neutral, closed-shell molecules.
In an experiment not dissimilar from others mentioned above, Paliwal and coauthors constructed a molecular torsion balance from an aryl ester with two conformational states. The folded state had a well-defined pi stacking interaction with a T-shaped geometry, whereas the unfolded state had no aryl–aryl interactions. The NMR chemical shifts of the two conformations were distinct and could be used to determine the ratio of the two states, which was interpreted as a measure of intramolecular forces. The authors report that a preference for the folded state is not unique to aryl esters. For example, the cyclohexyl ester favored the folded state more so than the phenyl ester, and the tert-butyl ester favored the folded state by a preference greater than that shown by any aryl ester. This suggests that aromaticity is not a strict requirement for favorable interaction with an aromatic ring.
Other evidence for non-aromatic pi stacking interactions results include critical studies in theoretical chemistry, explaining the underlying mechanisms of empirical observations. Grimme reported that the interaction energies of smaller dimers consisting of one or two rings are very similar for both aromatic and saturated compounds. This finding is of particular relevance to biology, and suggests that the contribution of pi systems to phenomena such as stacked nucleobases may be overestimated. However, it was shown that an increased stabilizing interaction is seen for large aromatic dimers. As previously noted, this interaction energy is highly dependent on geometry. Indeed, large aromatic dimers are only stabilized relative to their saturated counterparts in a sandwich geometry, while their energies are similar in a T-shaped interaction.
A more direct approach to modeling the role of aromaticity was taken by Bloom and Wheeler. The authors compared the interactions between benzene and either 2-methylnaphthalene or its non-aromatic isomer, 2-methylene-2,3-dihydronaphthalene. The latter compound provides a means of conserving the number of p-electrons while, however, removing the effects of delocalization. Surprisingly, the interaction energies with benzene are higher for the non-aromatic compound, suggesting that pi-bond localization is favorable in pi stacking interactions. The authors also considered a homodesmotic dissection of benzene into ethylene and 1,3-butadiene and compared these interactions in a sandwich with benzene. Their calculation indicates that the interaction energy between benzene and homodesmotic benzene is higher than that of a benzene dimer in both sandwich and parallel displaced conformations, again highlighting the favorability of localized pi-bond interactions. These results strongly suggest that aromaticity is not required for pi stacking interactions in this model.
Even in light of this evidence, Grimme concludes that pi stacking does indeed exist. However, he cautions that smaller rings, particularly those in T-shaped conformations, do not behave significantly differently from their saturated counterparts, and that the term should be specified for larger rings in stacked conformations which do seem to exhibit a cooperative pi electron effect.