A Hybrid Mechanism in Chiral Discrimination Induced by Crystallization of Supramolecular Compounds

Abstract

Host-guest complexes formed in aqueous medium between permethylated β-cyclodextrin (TMβ-CD) and racemic 1-(p-fluorophenyl)ethanol (p-F-PE) are studied. The crystalline complexes are characterized and their crystal structures are determined, revealing two sets of solid phases with specific abilities for chiral discrimination: on the one hand, a stable complete solid solution with two independent complexes per asymmetric unit exhibits a limited chiral recognition, and on the other hand, two metastable partial solid solutions with unusual 1:2 host-guest stoichiometries behave as diastereomeric complexes. The structural features of the 1:2 complexes and their study by means of molecular modeling show that these solid phases, described as cocrystals formed between one host-guest inclusion complex and one non-engulfed p-F-PE molecule, present a significant chiral discrimination occurring both inside the cyclodextrin and outside the macrocycle in a crystal lattice cavity. Therefore, the enantioselectivity observed in this system results from an interplay between molecular inclusion in the cyclodextrin and lattice inclusion. To our knowledge, it is the first report of such a hybrid mechanism. An overview of the crystal structures of the literature containing TMβ-CD is also achieved and allows their classification in four structural groups in relation to their crystal packing features.

Crystallization of molecular systems from solution: phase diagrams, supersaturation and other basic concepts

“…dC/dT o 0 (e.g. in water, [8][9][10] Na 2 SO 4 , Na 2 SeO 4 , Na 2 CO 3 Á1H 2 O, Li 2 SO 4 , permethylated b-cyclodextrin (TRIMEB) and all host-guest complexes characterized so far with this macrocycle, 11 Na in ammonia). The induction of the crystallization is thus performed by elevation of temperature.…”

Racemic drug resolution: a comprehensive guide

“…For instance, cyclodextrin has a different diffraction pattern before and aer complexation. [182][183][184][185] This is due to the crystalline nature of the drug changes aer complexation with cyclodextrin. Aer complexation, the appearance of a few new peaks whereas shiing and sharpening of old peaks can be observed.…”

A single-molecule electrical approach for amino acid detection and chirality recognition

“…However, the time scale of the association and disassociation process is usually at the nanosecond level, which is too transitory to be detected (28). Although most of host-guest recognitions involved complexes formed with the native -CD (29), the absence of intramolecular hydrogen bonds in PM--CDs, which may reduce the speed of molecular recognition, results in a higher flexibility and a more efficient enantio-discrimination (30,31). (ii) In comparison with PM--CDs and PM--CDs, PM--CDs have the more suitable cavity for amino acid detection on the basis of our previous unreported systematic exploration.…”