title: Combination of capillary electrophoresis, molecular modeling and NMR to study the enantioselective complexation of sulpiride with double cyclodextrin systems.
abstract: The enantioselective complexation of sulpiride by a number of cyclodextrins (CDs) was deeply investigated by different techniques with the aim of evaluating the role of the used chiral selectors involved in the enantioseparation of the eutomer levosulpiride (S-SUL) and its dextro-isomer by capillary electrophoresis (CE). A CE method was previously developed with the aim of determining the optical purity of S-SUL and was based on the use of a dual cyclodextrin system, made by sulfated-β-cyclodextrin (SβCD) and methyl-β-cyclodextrin (MβCD). In this paper, a molecular modeling study made it possible to explain the different affinity of sulpiride enantiomers for several CDs, which had been tested during the early phase of CE method development. The potential and the gain energy of the inclusion complexes between the enantiomers and neutral and charged CDs were calculated on the minimized conformations. The calculated docking energies indicated that the most stable complexes were effectively obtained with SβCD and MβCD. A correlation between CE migration time of the last migrating enantiomer S-SUL and the stability of analyte-neutral CDs complexes was postulated. Furthermore, two-dimensional rotating-frame Overhauser effect spectroscopy NMR (2-D ROESY) experiments were carried out, which clearly indicated the formation of complexes and suggested the inclusion of the benzene sulfonamide moiety of S-SUL inside the hydrophobic cavity of the CDs.
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Via U. Schiff 6, 50019, Sesto Fiorentino, Florence, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Melani
authors.affiliation: Department of Chemistry "U. Schiff", University of Florence, Via U. Schiff 6, 50019, Sesto Fiorentino, Florence, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Pasquini
authors.affiliation: Department of Chemistry "U. Schiff", University of Florence, Via U. Schiff 6, 50019, Sesto Fiorentino, Florence, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Caprini
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gotti
authors.affiliation: Department of Chemistry "U. Schiff", University of Florence, Via U. Schiff 6, 50019, Sesto Fiorentino, Florence, Italy. Electronic address: serena.orlandini@unifi.it.
authors.forename: Serena
authors.initials: S
authors.lastname: Orlandini
authors.affiliation: Department of Chemistry "U. Schiff", University of Florence, Via U. Schiff 6, 50019, Sesto Fiorentino, Florence, Italy. Electronic address: sandra.furlanetto@unifi.it.
authors.forename: Sandra
authors.initials: S
authors.lastname: Furlanetto
mesh_terms: D002021:Buffers; D003505:Cyclodextrins / Q000032:analysis*; D019075:Electrophoresis, Capillary / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D012984:Software; D013237:Stereoisomerism; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry
chemical_list: D002021:Buffers; D003505:Cyclodextrins; D013469:Sulpiride; C078143:levosulpiride
keywords: Capillary electrophoresis; Dual cyclodextrin systems; Inclusion complex; Levosulpiride; Molecular modeling; NMR