The Fundamental Nature of Pi Interactions

Weak interactions, such as the noncovalent interactions governing drug binding and the structures of organic crystals, are very challenging to understand. Experimentally, these interactions are often seen in complex environments, where it can be difficult to pick out only the interaction of interest. Theoretically, they require very accurate quantum-mechanical modeling for reliable results. Definitive theoretical investigations of π-π, alkyl-π, and sulfur-π interactions which elucidate the strength, geometrical preferences, and fundamental nature of these prototype biomolecular interactions will be presented. In particular, it is shown that the current paradigm for understanding π- π interactions, which emphasizes electrostatic interactions, fails qualitatively in light of high-level quantum-mechanical results. Applications to SH/π interactions in proteins and the first ``chemical accuracy'' computation of the lattice energy of an organic crystal (benzene) will be presented. Advances in theoretical methods for non-bonded interactions in larger molecules will also be discussed.