Aromatic interactions in solution

Abstract

Non-covalent interactions underpin a vast array of molecular recognition phenomena including drug binding and asymmetric catalysis. Interactions involving aromatic rings are particularly pervasive. Therefore, there is demand for a more thorough understanding of the physicochemical nature of these interactions Chapter 1 begins by reviewing the physicochemical basis of molecular recognition. The utility of molecular balances (and model supramolecular complexes) as platforms to measure and characterise non-covalent interaction is explored using illustrative examples. Chapter 2 introduces a novel class of molecular balances based on a terphenyl motif. These balances are then used to evaluate the nature of polycyclic aromatic stacking interactions. No solvent effect is observed, and the strength of the interaction is found to scale with the change in solvent accessible surface area between the two conformers. Electronic structure calculations and SAPT energy decomposition reveal that van der Waals interactions are the primary driving force for the folding equilibrium. Chapter 3 seeks to evaluate the consistent bias towards the anti-conformer observed in the terphenyl molecular balances. Ab initio calculations suggest that is due, at least in part, to favourable CH⋯π interactions that are formed in the anti-conformer. Balances that vary the nature of the CH⋯π interactions while preserving the stacking interaction are introduced, resulting in a solvent effect. A simple model is used to dissect out the solvent-independent interaction and SAPT energy decomposition is used to evaluate their nature. Chapter 4 investigates the effects of fluorination on both aromatic stacking and CH⋯π interactions. Molecular balances featuring fluorinated aromatic rings and/or methyl groups are compared. Molecular balances featuring tetra- or pentafluorinated rings exhibit a solvent effect that does not appear to be the result of a single dominant factor. Pairwise comparisons of SAPT calculations between analogous compounds are used to evaluate the differences between fluorous and non-fluorous interactions.