Dispersion Interactions in Condensed Phases and inside Molecular Containers

The past decade has seen significant progress in the understanding and appreciation of the importance of London dispersion interactions (LDIs) in supramolecular systems and solutions. The Slater-Kirkwood formula relates LDIs to the molecular polarizabilities of the two interacting molecular species (alpha) and their interaction distance (a dependence of R-6). When advancing arguments related to intermolecular interactions, it is frequently assumed that molecules with larger molecular polarizabilities are more amenable to larger LDIs. However, arguments related to molecular polarizabilities are not always transferable to the condensed phase. In fact, the underlying bulk and molecular polarizabilities of common solvents show opposing trends. The intuitive concept that aromatic molecules are more polarizable than saturated hydrocarbons and that perfluorinated molecules are less polarizable than saturated hydrocarbons applies to the condensed phase only. When treating association phenomena in solution, where LDIs are generally very attenuated, the use of bulk polarizabilities is recommended, which are experimentally accessible through either refractive index measurements or suitable solvatochromic probes. Such probes can also be used to assess polarizabilities inside molecular container compounds, such as cucurbit[n]urils (CBn), cyclodextrins, calixarenes, and hemicarcerands. These macrocyclic cavities can have extreme microenvironments. For example, the inner concave phase of CB7 has been shown to be weakly polarizable, falling in between the gas phase and perfluorohexane; those of beta-cyclodextrin and p-sulfonatocalix[4]arene have been found to be similarly polarizable as water and alkanes, respectively, and the inside of hemicarcerands displays a very large bulk polarizability, exceeding that of diiodomethane. CBn compounds are privileged molecular container compounds, which we exemplify in this Account through case studies. (1) CBn macrocycles are prime water-soluble receptors for hydrocarbons, allowing for the reduction of the binding free energies to two components: the hydrophobic effect and dispersion interactions. To understand hydrocarbon binding, we initiated the HYDROPHOBE challenge, which revealed the shortcomings of both quantum-chemical and molecular dynamics approaches. (2) The smallest CBn receptor, CB5, is uniquely suited to bind the entire noble gas series, where hydrophobic effects and dispersion interactions operate in opposite directions. CB5 was revaled to be a unique synthetic receptor for noble gases, with the dominant driving force being the recovery of the cavitation energies for the hydration of noble gases in aqueous solution. Computational methods that encounter challenges in predicting hydrocarbon affinities and trends for CB6 and CB7 perform well for noble gases binding to CB5. (3) The larger homologue, CB8, allows one to set up intermolecular interaction chambers by the encapsulation of a (first) aromatic guest, thereby tuning LDIs inside the receptor cavity. In this manner, CB8 can be modulated to preferentially bind unsaturated and aromatic rather than saturated hydrocarbons, while the unmodified cavities of the smaller macrocycles CB6 and CB7 show selective binding of saturated hydrocarbons. (4) The (charged) host-guest complexes of CBn hosts are sufficiently stable in the gas phase, allowing for the study of the influence of LDIs on inner-phase chemical reactions. These studies are particularly interesting for the theoretical analysis of isolated host-guest LDIs, as experimental and computational data are directly comparable in the gas phase due to the absence of the solvation effect.