This review clarifies terms of aromatic interactions and proposes a unified description, indicating potential misunderstandings.
The terms "π-stacking" and "π-π stacking" are widely used to describe attractive interactions between aromatic molecules, yet they are often interpreted as implying a distinct, π-orbital-based attractive force and a preference for a perfectly face-centered stacking geometry. Over the last three decades, structural and theoretical studies have shown that neutral, closed-shell aromatic systems instead favor T-shaped and parallel-displaced geometries and that their interaction energies can be rationalized entirely in terms of the same noncovalent forces that govern molecular interactions in general. In typical ground-state aromatic complexes, there is negligible π-orbital mixing and no demonstrable additional attractive force that is unique to π electrons. Consequently, the mechanistic content of the terms "π-stacking" and "π-π stacking" is, in most cases, ill-defined and potentially misleading when interpreted as describing a special class of interactions. Here, we advocate replacing such usage with a description in terms of Electrostatic, Dispersion, Desolvation, Induction, and Exchange-repulsion contributions (EDDIE). We further discuss those specific situations─such as charge-transfer absorptions, excitonically coupled H- and J-aggregates, and true charge-transfer salts─in which π-orbital mixing is appreciable and terminology invoking "π-stacked" systems remains physically meaningful, though still not required to describe the underlying binding forces.
No takes yet. Share an insight, caveat, or question.
Xiao et al. (2026) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: