title: Comparative evaluation of the chiral recognition potential of single-isomer sulfated beta-cyclodextrin synthesis intermediates in non-aqueous capillary electrophoresis.
abstract: The enantioselectivity of neutral single-isomer synthetic precursors of sulfated-β-cyclodextrins was studied. Four neutral single-isomer cyclodextrins substituted on the secondary side with acetyl and/or methyl functional groups, heptakis(2-O-methyl-3,6-dihydroxy)-β-cyclodextrin (HM-β-CD), heptakis(2,3-di-O-acetyl-6-hydroxy)-β-cyclodextrin (HDA-β-CD), heptakis(2,3-di-O-methyl-6-hydroxy)-β-cyclodextrin (HDM-β-CD), heptakis(2-O-methyl-3-O-acetyl-6-hydroxy)-β-cyclodextrin (HMA-β-CD), and their sulfated analogs the negatively charged heptakis(2,3-di-O-methyl-6-sulfato)-β-cyclodextrin (HDMS-β-CD) and heptakis(2,3-di-O-acetyl-6-sulfato)-β-cyclodextrin (HDAS-β-CD) were investigated by non-aqueous capillary electrophoresis in the view of enantiodiscrimination for various drugs and related pharmaceutical compounds. The focus of the present work was on the chiral selectivity studies of the neutral derivatives, which are the synthesis intermediates of the sulfated products. The chiral recognition experiments proved that among the neutral compounds the HMA-β-CD shows remarkable enantioselectivity towards chiral guests in non-aqueous capillary electrophoresis, while HM-β-CD, HDA-β-CD and HDM-β-CD failed to resolve any of the 25 studied racemates under the applied experimental conditions. In order to get deeper insight into the molecular interactions between the studied single-isomer cyclodextrin and chiral fluoroquinolones (ofloxacin, gatifloxacin and lomefloxacin) and β-blockers (propranolol),1H and ROESY NMR experiments were performed. The 2-O-methylation in combination with the 3-O-acetylation of the host was evidenced to exclusively carry the essential spatial arrangement for chiral recognition.
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: 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; 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: András
authors.initials: A
authors.lastname: Darcsi
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. Electronic address: beni.szabolcs@pharma.semmelweis-univ.hu.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Béni
mesh_terms: D000107:Acetylation; D019075:Electrophoresis, Capillary; D024841:Fluoroquinolones / Q000737:chemistry; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D011433:Propranolol / Q000737:chemistry; D013237:Stereoisomerism; D047392:beta-Cyclodextrins / Q000138:chemical synthesis*
chemical_list: D024841:Fluoroquinolones; D007202:Indicators and Reagents; D047392:beta-Cyclodextrins; C447200:heptakis(2,3-diacetyl-6-sulfo)-cyclodextrin; C400661:heptakis(2,3-dimethyl-6-sulfato)cyclodextrin; D011433:Propranolol; C031215:betadex
keywords: (1)H NMR; Enantioseparation; Host-guest interaction; Non-aqueous chiral capillary electrophoresis; ROESY NMR; Single-isomer cyclodextrin