The Impact of London Dispersion Interactions in Solution: Bring [a Molecular] Balance to the [LD] Force!

Abstract

The contribution of London Dispersion (LD) to the intramolecular folding behavior of a cyclooctatetraene (COT)-based molecular balances in a variety of solvents was investigated. As part of this investigation, a well-defined system, represented by a tert-butyl dimer with an intramolecular distance of 2.44 Å was synthesized. The folding behavior of this molecular balance was then investigated in various solvents with increasing solvent polarizability (SP) to examine the contribution of London interactions. We showed that the free enthalpy of the isomerization reaction in each solvent follows approximately the same value. Gibbs free energy can be readily measured by determination of the ratio of 1,4- to 1,6-isomers. It was found that the entropy in each solvent system is responsible for the diminishing effect on ΔG values. The answer to the question of Yang et al. “How much does LD contribute to molecular recognition in solution?” is that “It depends!” The lowest ratio of 1,4- and 1,6-isomers was found in purely aliphatic solvents, this may indicate a compensating effect of dispersion interactions between the solvent and the balance. DMSO and chloroform clearly showed a preference for the 1,6-isomer. However, it became clear through additional energy decomposition analyzes (EDAs) that LD is the predominant force responsible for folding. The extension of the concept was investigated by the synthesis of adamantyl and diamantyl COT derivatives. The molecular balances still have an attractive distance of 2.4 Å for dispersion, but the polarizabilities and the expansion regarding the solvent accessible surface (SAS) of the substituents become significantly larger, which allows more interaction with the surrounding solvent. Longer aliphatic chain hydrocarbons (n-hexane, n-octane and n-dodecane) were therefore chosen as solvents to suit the growth of the derivatives. In collaboration with the Max-Planck Institute for Coal Research, computations at the highest level were carried out using implicit and explicit solvent models to determine the influence of the solvents on the folding behavior. The computational and experimental results lead to the conclusion that an adhesion occurs through the solvent and that the “rigid rotors” of the diamondoid derivatives make an exclusive contribution to the entropy. In every study, the folded derivative is always preferred.