Handle with care: pi - pi stacking

30 April 2008 - Physical chemistry

pistackingGrimme2008.svg Pi - pi stacking is a popular chemistry concept describing how aromatic molecules are stabilized when oriented face-to-face as in a stack of coins. It explains how certain supramolecular structures are formed and especially in biology it explains the finer points of base pairing in DNA.

The origins of pi stacking are unclear. In a simple bonding model the interaction results from favorable overlap of the aromatic pi-orbitals. But in a recent article (DOI) Stephan Grimme points out this is a widely held misconception. As one of the offenders he cites the November 2007 wikipedia pi stacking article which must be the first time Wikipedia gets a mention in the scientific literature but for the wrong reasons.

In his article Grimme investigates the true origin of pi stacking and questions if it really exists. After all, many intermolecular interactions can equally well be explained with conventional dispersion forces which arise from statistical fluctuations in electron density.

In a series of computations Grimme compares a group of aromatic compounds (benzene, anthracene and the two higher acenes) with their saturated all-trans counterparts (e.q. cyclohexane, decaline etc.) with respect to intermolecular separation and stabilization energy. Sure enough, in the aromatic series this distance decreases as the stabilization energy increases but interestingly for the first two members the stabilization energy is similar be it unsaturated or saturated. So no special pi effect there. On the other hand for the higher members genuine pi stacking is a reality and is dominated by dispersion.

Therefore handle with care, with less than 11 atoms all a molecule experiences are plain old-fashioned van der Waals forces. Biomolecules such as purines still stack but without the pi pi.