Supramolecular Chemistry Controlled by Conformational Space during Structure Direction of Nanoporous Materials: Self-Assembly of Ephedrine and Pseudoephedrine

Abstract

In an attempt to produce chiral solids, where chirality arises from an asymmetric ordering of the spatial distribution of dopants, we have studied the supramolecular aggregation of π–π-type interactions between aromatic rings of two closely related diastereoisomers, (1R,2S)-ephedrine and (1S,2S)-pseudoephedrine, during structure direction of the microporous AFI large-pore aluminophosphate framework. Despite their very similar molecular structures, differing only in the stereochemistry of the hydroxyl substituent, fluorescence spectroscopy clearly shows completely different aggregation behaviors of the two isomers, with ephedrine displaying a much stronger aggregation trend than pseudoephedrine in aqueous solution; interestingly, this supramolecular behavior is reproduced when the molecules are occluded within the AFI framework during crystallization. A molecular mechanics study of the conformational behavior of the two chiral flexible molecules, both in a vacuum and in aqueous solution, revealed that the lower trend of pseudoephedrine to form supramolecular aggregates is caused by the occurrence of a particular conformation with a folded molecular structure. This conformation, which is stable for pseudoephedrine but not for ephedrine, provokes steric hindrance that prevents the approaching of a neighboring molecule to form an aggregate, hence providing an explanation for the experimental observations. Our work represents the first example in which the conformational space of a molecule determines its supramolecular aggregation behavior during structure direction and could play a role in molecular-recognition phenomena in host–guest systems.