Comparative analysis of the full set of methylated β‐cyclodextrins as chiral selectors in capillary electrophoresis

Abstract

Comparative analysis of the full set of methylated ␤-cyclodextrins as chiral selectors in capillary electrophoresisThe chiral separation ability of the full library of methylated-␤-cyclodextrins towards pharmacologically significant racemic drugs including basic compounds was studied by chiral CE. The syntheses of all the methylated, single isomer ␤-cyclodextrins were revised and optimized and the aqueous solubility of the derivatives was unambiguously established. The three most relevant commercially available methylated isomeric mixtures were also included in the screening, so a total of ten various methylated CDs were investigated. The effects of the selector concentration on the enantiorecognition properties at acidic pH were investigated. Among the dimethylated ␤-cyclodextrins, the heptakis (2,6-di-Omethyl)-␤-cyclodextrin isomer (2,6-DIMEB) resulted to be the most versatile chiral selector. Terbutaline was selected as a model compound for the in-depth investigation of host-guest enantiodiscrimination ability. The association constants between the two terbutaline enantiomers and 2,6-DIMEB were determined in order to support that the enantioseparation is driven by differences is host-guest binding. The migration order of the enantiomers was confirmed by performing spiking experiments with the pure enantiomers. 1D and 2D NMR spectroscopy was applied to the 2,3-, and 2,6-DIMEB/terbutaline systems to rationalize at molecular level the different enantioseparation ability of the dimethylated ␤-cyclodextrin selectors.

Separation of terbutaline enantiomers in capillary electrophoresis with neutral cyclodextrin‐type chiral selectors and investigation of the structure of selector‐selectand complexes using nuclear magnetic resonance spectroscopy

“…Acetylation of CDs represents a very interesting synthetic tool for understanding chiral recognition mechanisms [6, 10]. This is because it has been observed that the chiral recognition ability of acetylated CDs commonly improves if compared to their native precursors.…”

“…The combination of CE and NMR spectroscopy is a well‐established tandem for a better understanding the mechanisms of weak intermolecular interactions [1–13]. In particular, CE is not only a powerful separation technique but due to its high separation efficiency it also allows to detect those fine intermolecular interactions that are commonly invisible with other instrumental (separation or non‐separation) techniques.…”

“…In particular, CE is not only a powerful separation technique but due to its high separation efficiency it also allows to detect those fine intermolecular interactions that are commonly invisible with other instrumental (separation or non‐separation) techniques. At the same time, CE does not provide a direct information regarding the stoichiometry and structure of selector–selectand (ligand–receptor) associates in solution, while this can be achieved with NMR spectroscopy [1–13]. Thus, these two techniques are complementary to each other and, in addition, both of them provide information regarding the binding constants of selector–selectand associates.…”

“…Thus, these two techniques are complementary to each other and, in addition, both of them provide information regarding the binding constants of selector–selectand associates. The abovementioned reasons made simultaneous application of CE and NMR spectroscopy quite popular in past for the understanding of enantiomer recognition mechanisms of many chiral host molecules and, in particular, cyclodextrins (CD) [1–13].…”

Chemiluminescence of coelenterazine catalyzed by cyclodextrins as a luminescence reference standard for luminometers v1

“…The distributions of substitutions in different methylated β-CD derivatives are nicely illustrated in the Figure 1 of the following paper: (Varga et al, 2019). A precise determination of pH and the use of a pH reference standard in essential, because the CTZ chemiluminescence depends on pH.…”