Understanding the mechanisms of enantiomer binding and recognition with cyclodextrins by integrating capillary electrophoresis, nuclear magnetic resonance and quantum mechanics

Multiple factors may impact enantiorecognition ability of CDs, and the validation of computational tools by using suitable experimental data is a critical point. The main advantage of using capillary electrophoresis (CE) for this purpose relies on its higher sensitivity to detect weak noncovalent intermolecular interactions compared to any other technique. In this study, we used CE enantioseparations of tetramisole with β-CD, heptakis(2,3-di-O-methyl)-β-CD, heptakis(2,3-di-O-acetyl)-β-CD and heptakis(2-O-methyl-3-O-acetyl)-β-CD as benchmark separation systems aiming at investigating the molecular bases of these processes by NMR spectroscopy and quantum mechanics (QM) methods. The aim of this study was explaining the subtle differences observed in enantiomer migration order, that means enantiomer affinity pattern of tetramisole toward the used CDs, migration times, and selectivity values. A good correlation between experimental and theoretical data was obtained along with noncovalent interactions patterns fully consistent with the CE outcomes. Significant differences in the enantioselective recognition ability were observed between β-CD and heptakis(2,3-di-O-acetyl)-β-CD in CE, which correlated very well with the recognition model derived from NMR spectroscopy and QM. Importantly, the introduction of dispersion corrections in the used QM model chemistry provided results in better agreement with the experimental observations for the complexes of tetramisole with the acetylated β-CDs.