title: Single-isomer carboxymethyl-γ-cyclodextrin as chiral resolving agent for capillary electrophoresis.
abstract: Herein we report on the synthesis, characterization and the novel capillary electrophoretic use of octakis-(2,3-di-O-methyl-6-O-carboxymethyl)-γ-cyclodextrin sodium salt (ODMCM). ODMCM is the first single-isomer carboxymethyl-γ-cyclodextrin that is fully methylated on its secondary side and carries ionizable carboxymethyl functions on its primary side. ODMCM was prepared with high isomeric purity through a four-step synthetic procedure. The purity of each intermediate was characterized by appropriate chromatographic methods, while the isomeric purity of the carboxymethylated product was determined by an HPLC method using a CD-Screen-IEC column and by a capillary electrophoretic method using indirect UV detection, as well. The structural identification of the ODMCM was carried out by 1D, 2D NMR spectroscopy and ESI-MS. The acid-base characterization of the chiral selector was carried out by1H NMR-pH titration. The chiral separation ability of the synthesized selector was studied by chiral capillary electrophoresis. ODMCM was used as a background electrolyte additive to separate enantiomers of representative pharmacologically significant model molecules such as propranolol, citalopram, ketamine, tapentadol and dapoxetine. The effects of the selector concentration and the pH of the background electrolyte on the enantiorecognition properties were investigated.1H NMR spectroscopy was further applied to get deeper insight of the host-guest inclusion complex formation. The pH-dependent enantioselectivity of this new single-isomer chiral selector was demonstrated by chiral capillary electrophoresis and1H NMR spectroscopy.
authors.affiliation: CycloLab, Cyclodextrin R&D Ltd, Budapest, H-1097, Illatos út 7, Hungary; Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 128 43, Prague 2, Czech Republic.
authors.forename: Gábor
authors.initials: G
authors.lastname: Benkovics
authors.affiliation: Department of Pharmacognosy, Semmelweis University, Budapest, H-1085, Üllői út 26, Hungary.
authors.forename: Ida
authors.initials: I
authors.lastname: Fejős
authors.affiliation: Department of Pharmacognosy, Semmelweis University, Budapest, H-1085, Üllői út 26, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Darcsi
authors.affiliation: CycloLab, Cyclodextrin R&D Ltd, Budapest, H-1097, Illatos út 7, Hungary.
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Varga
authors.affiliation: CycloLab, Cyclodextrin R&D Ltd, Budapest, H-1097, Illatos út 7, Hungary.
authors.forename: Milo
authors.initials: M
authors.lastname: Malanga
authors.affiliation: CycloLab, Cyclodextrin R&D Ltd, Budapest, H-1097, Illatos út 7, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Fenyvesi
authors.affiliation: CycloLab, Cyclodextrin R&D Ltd, Budapest, H-1097, Illatos út 7, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Sohajda
authors.affiliation: CycloLab, Cyclodextrin R&D Ltd, Budapest, H-1097, Illatos út 7, Hungary.
authors.forename: Lajos
authors.initials: L
authors.lastname: Szente
authors.affiliation: Department of Pharmacognosy, Semmelweis University, Budapest, H-1085, Üllői út 26, Hungary.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Béni
authors.affiliation: CycloLab, Cyclodextrin R&D Ltd, Budapest, H-1097, Illatos út 7, Hungary. Electronic address: szeman.j@cyclolab.hu.
authors.forename: Julianna
authors.initials: J
authors.lastname: Szemán
mesh_terms: D002851:Chromatography, High Pressure Liquid; D019075:Electrophoresis, Capillary; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D047408:gamma-Cyclodextrins / Q000737:chemistry*
chemical_list: D007202:Indicators and Reagents; C092583:carboxymethyl-gamma-cyclodextrin; D047408:gamma-Cyclodextrins
keywords: (1)H NMR; Chiral capillary electrophoresis; Cyclodextrin synthesis; Enantioseparation; Host-guest interaction; Single-isomer