title: Combination of capillary electrophoresis, molecular modelling and nuclear magnetic resonance to study the interaction mechanisms between single-isomer anionic cyclodextrin derivatives and basic drug enantiomers in a methanolic background electrolyte.
abstract: In order to improve our knowledge of the mechanisms of enantiomer recognition pattern in nonaqueous systems, an approach combining nonaqueous CE (NACE), molecular modelling and NMR was undertaken. Bupivacaine and propranolol were selected as model compounds and their interactions with two single-isomer highly charged β-CD derivatives, namely heptakis(2,3-di-O-methyl-6-O-sulfo)-β-CD (HDMS-β-CD) and heptakis(2,3-di-O-acetyl-6-O-sulfo)-β-CD (HDAS-β-CD), were studied. The CD-bupivacaine complexes were evaluated by 2-D Rotating-frame Overhauser Effect SpectroscopY (ROESY) experiments. From these experiments, it can be assumed that inclusion complexes are not formed, whatever the CD derivative used. Molecular modelling was performed at the RHF/MINI-1 or B3LYP/6-31G(d) level. External as well as inclusion type complexes with the alkyl chain of propranolol into both CD cavities were located. Interaction energies calculated for bupivacaine and propranolol correlated with the enantiomer migration order observed in the NACE experiments using both anionic CD derivatives. The interaction of propranolol with HDMS-β-CD or HDAS-β-CD gives rise to a family of external and inclusion complexes in which some are more probably obtained.
authors: Laboratory of Analytical Pharmaceutical Chemistry, Dept. of Pharmaceutical Sciences, CIRM, University of Liège, CHU, B36, B-4000 Liège 1, Belgium. acservais@ulg.ac.be
authors: Anne-Catherine
authors: AC
authors: Servais
authors: Anne
authors: A
authors: Rousseau
authors: Georges
authors: G
authors: Dive
authors: Michel
authors: M
authors: Frederich
authors: Jacques
authors: J
authors: Crommen
authors: Marianne
authors: M
authors: Fillet
mesh_terms: D002045:Bupivacaine / Q000737:chemistry; D019075:Electrophoresis, Capillary / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D000432:Methanol / Q000737:chemistry*; D008958:Models, Molecular; D011433:Propranolol / Q000737:chemistry; D013237:Stereoisomerism; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D047392:beta-Cyclodextrins; C447200:heptakis(2,3-diacetyl-6-sulfo)-cyclodextrin; C400661:heptakis(2,3-dimethyl-6-sulfato)cyclodextrin; D011433:Propranolol; D000432:Methanol; D002045:Bupivacaine