title: Mechanistic considerations of enantiorecognition on novel Cinchona alkaloid-based zwitterionic chiral stationary phases from the aspect of the separation of trans-paroxetine enantiomers as model compounds.
abstract: The enantiomers of trans-paroxetine were separated on four chiral stationary phases (CSPs) based on chiral zwitterionic Cinchona alkaloids fused with (R,R)- or (S,S)-trans-2-aminocyclohexanesulfonic acid. The enantioseparations were carried out in polar-ionic or in hydro-organic mobile phases with MeOH/THF, MeCN/THF, MeCN/THF/H2O and MeOH/MeCN/THF containing organic acid and base additives, in the temperature range 0-50°C. The effects of the mobile phase composition, the natures and concentrations of the additives and temperature on the separations were investigated. Thermodynamic parameters were calculated from plots of ln α vs 1/T. Δ(ΔH°) ranged between -3.0 and +1.5 kJ mol(-1), and Δ(ΔS°) between -8.8 and +5.9 J mol(-1)K(-1). The enantioseparation was generally enthalpically controlled, the retention factor and separation factor decreasing with increasing temperature, but entropically controlled separation was also observed. The elution sequences of the paroxetine enantiomers on the two pairs of pseudo-enantiomeric CSPs were investigated, and an attempt was made to explain the observed anomalies in silico in order to gain an insight into the underlying molecular recognition events between the four chiral selectors and the analyte enantiomers.
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, H-6720 Szeged, Dóm tér 7, Hungary; Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös u. 6, Hungary.
authors.forename: Nóra
authors.initials: N
authors.lastname: Grecsó
authors.affiliation: Department of Organic Chemistry, University of Chemistry and Technology Prague, Technická 5, CZ-16628 Prague, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Kohout
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, Via Fabretti 48, 06123 Perugia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Carotti
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, Via Fabretti 48, 06123 Perugia, Italy.
authors.forename: Roccaldo
authors.initials: R
authors.lastname: Sardella
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, Via Fabretti 48, 06123 Perugia, Italy.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Natalini
authors.affiliation: Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös u. 6, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Fülöp
authors.affiliation: Department of Analytical Chemistry, University of Vienna, Währingerstrasse 38, 1090 Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lindner
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, H-6720 Szeged, Dóm tér 7, Hungary.
authors.forename: Antal
authors.initials: A
authors.lastname: Péter
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, H-6720 Szeged, Dóm tér 7, Hungary. Electronic address: ilisz@chem.u-szeged.hu.
authors.forename: István
authors.initials: I
authors.lastname: Ilisz
mesh_terms: D002930:Cinchona Alkaloids / Q000737:chemistry*; D008956:Models, Chemical; D017374:Paroxetine / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D002930:Cinchona Alkaloids; D017374:Paroxetine
keywords: Enantiomer separation; High-performance liquid chromatography (HPLC); Molecular dynamic simulations; Zwitterionic chiral stationary phases; trans-Paroxetine enantiomers