Arene-arene interactions have attracted much attention. Pi-stacking (also called
π–π stacking) refers to the presumptively attractive,
noncovalent pi interactions between the
pi bonds of
aromatic rings, because of
orbital overlap. According to some authors direct stacking of aromatic rings (the "sandwich interaction") is
electrostatically repulsive. More commonly observed are either a
staggered stacking (parallel displaced) or
pi-teeing (perpendicular T-shaped) interaction both of which are electrostatic attractive For example, the most commonly observed interactions between aromatic rings of amino acid residues in proteins is a staggered stacked followed by a perpendicular orientation. Sandwiched orientations are relatively rare. Pi stacking is repulsive as it places carbon atoms with partial negative charges from one ring on top of other partial negatively charged carbon atoms from the second ring and hydrogen atoms with partial positive charges on top of other hydrogen atoms that likewise carry partial positive charges. These staggered stacking and π-teeing interactions between aromatic rings are important in
nucleobase stacking within
DNA and
RNA molecules,
protein folding,
template-directed synthesis,
materials science, and
molecular recognition. Despite the wide use of term pi stacking in the scientific literature, there is no theoretical justification for its use.
Benzene dimer The
benzene dimer is the prototypical system for the study of pi stacking, and is experimentally bound by 8–12 kJ/mol (2–3 kcal/mol) in the gas phase with a separation of 4.96 Å between the centers of mass for the T-shaped dimer.
X-ray crystallography reveals perpendicular and offset parallel configurations for many simple aromatic compounds. Analysis of the aromatic amino acids phenylalanine, tyrosine, histidine, and tryptophan indicates that dimers of these side chains have many stabilizing interactions at distances larger than the average van der Waals radii. The local C–H dipole means that there is positive charge on the atoms in the ring and a correspondingly negative charge representing an electron cloud above and below the ring. The quadrupole moment is reversed for
hexafluorobenzene due to the electronegativity of fluorine. The benzene dimer in the sandwich configuration is stabilized by London dispersion forces but destabilized by repulsive quadrupole/quadrupole interactions. By offsetting one of the benzene rings, the parallel displaced configuration reduces these repulsive interactions and is stabilized. The large polarizability of aromatic rings lead to
dispersive interactions as major contribution to stacking effects. These play a major role for interactions of nucleobases e.g. in
DNA. The T-shaped configuration enjoys favorable quadrupole/quadrupole interactions, as the positive quadrupole of one benzene ring interacts with the negative quadrupole of the other. The benzene rings are furthest apart in this configuration, so the favorable quadrupole/quadrupole interactions evidently compensate for diminished
dispersion forces. According to one model, electron-withdrawing substituents lowers the negative quadrupole of the aromatic ring and thereby favor parallel displaced and sandwich conformations. By contrast, electron donating groups increase the negative quadrupole, which may stabilize a T-shaped configuration with the proper geometry. They used a simple mathematical model based on sigma and pi atomic charges, relative orientations, and van der Waals interactions to qualitatively determine that
electrostatics are dominant in substituent effects. 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. 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. == See also ==