Effectively enhancing the enantioseparation ability of β-cyclodextrin derivatives by de novo design and molecular modeling

Abstract

Rational engineering of native β-CD as an ideal chiral selector for a definite analyte in capillary electrophoresis represents a challenge in separation science. Herein, a rational and systematic strategy that combines the de novo design and molecular modeling is firstly described to expedite the manipulation and selection of effective selector for enantioseparation in capillary electrophoresis. Using β-adrenoreceptor agonists as model analytes, we demonstrate how this strategy efficiently improves the enantiorecognition in chiral discrimination sites of inclusion complexes. The evolved β-CD derivative could be utilized as a chiral receptor to achieve the effective enantioseparation (R > 1.5) of racemic β-adrenoreceptor agonists. We highlight a novel strategy for efficiently and rapidly manipulating native CD based on the characteristics of analyte so as to gain an excellent chiral selector.

Noncovalent Complexes of Cyclodextrin with Small Organic Molecules: Applications and Insights into Host–Guest Interactions in the Gas Phase and Condensed Phase

“…This model is especially useful for explaining the recognition of guest molecules lacking notable interaction parts in the CD complex system [ 24 ]. Various strategies have been utilized to elucidate the interaction mechanism, namely, nuclear magnetic resonance (NMR) spectroscopic techniques (e.g., nuclear Overhauser effect (NOE) and rotating-frame Overhauser enhancement (ROESY) spectroscopy) and theoretical calculations (e.g., molecular dynamics (MD), semi-empirical, and density functional theory (DFT) methods) [ 33 , 34 , 35 , 36 ].…”

Advances of capillary electrophoresis enantioseparations in pharmaceutical analysis (2017–2020)

“…In several of the examples compiled in Table 1, differences in the structures of the complexes for a given analyte depending on the type of CD were observed. For example, the enantioseparation of terbutaline (TER) by CDs has been studied in combination with NMR spectroscopy with regard to α-CD, β-CD, γ-CD, heptakis (2,3- [78]. In most cases, (R)-TER migrated before (S)-TER in acidic BGEs except for α-CD, HDA-β-CD and HMDS-β-CD where the migration order was S > R and 2,3-DM-β-CD, which did not resolve the enantiomers.…”

Chiral Selectors in Capillary Electrophoresis: Trends during 2017–2018

“…Other commercially-available modified CDs or laboratory-prepared modified CDs with known synthesis were reported. These were hydroxypropyl-α-CD [23], sulphated-α-CD [21], (2-carboxy-ethyl)-β-CD [34], heptakis(2,3-di- O -acetyl)-β-CD [35], heptakis(2,6-di- O -methyl)-β-CD, heptakis-(2,3,6-tri- O -methyl)-β-CD [36,37], heptakis(2- O -methyl-3,6-di- O -sulfo)-β-CD, heptakis(2,3-di- O -methyl-6- O -sulfo)-β-CD, heptakis(2,3-di- O -acetyl-6- O -sulfo)-β-CD [36], heptakis-6-sulfato-β-CD [38], heptakis-(6- O -sulfobutylether)-β-CD sodium salt [39], heptakis (2,6-di- O -[2-hydroxy-3-(sulfo-amino)propoxy])-β-CD [40], 2-hydroxypropyl-β-CD [37] octa(6- O -sulfo)-γ-cyclodextrin [41], lysine-bridged hemispherodextrin [42], methylated β-CD [43], mono-6-deoxy-6-(4-amino-1,2,4-triazolium)-β-CD chloride [44], mono-6-deoxy-6-(3-methylimidazolium)-β-CD tosylate [45], quaternary ammonium β-CD [46], carboxymethyl-β-CD [47,48], hydroxypropyl-γ-CDs [21,34], sulphated-γ-CDs [21] and highly sulphated-γ-CDs [49]. Sulfobutylether-β-CDs are also available commercially as Captisol ® and were applied successfully in the enantiomeric separation of neutral and basic drugs, but not towards negatively charged analytes in EKC [50].…”

“…During this review period, ten studies utilised molecular modelling, with the intention of understanding chiral recognition mechanism and elution migration order [22,32,35,44,60,62,72,73,94,95]. Molecular modelling has also been utilised to design new CSs [40].…”