title: Combinatorial effects of the configuration of the cationic and the anionic chiral subunits of four zwitterionic chiral stationary phases leading to reversal of elution order of cyclic β3-amino acid enantiomers as ampholytic model compounds.
abstract: In a systematic way enantioseparations of non-methylated and the corresponding N-monomethylated ampholytic cyclic ß3-amino acids were carried out on four zwitterionic chiral stationary phases (CSPs; ZWIX(+)™, ZWIX(-)™, ZWIX(+A), ZWIX(-A)). CSPs were based on the combinations of quinine and quinidine as the cationic and of (R,R)- and (S,S)-aminocyclohexane sulfonic acid as the anionic sites. In polar-ionic mobile phase systems, the effects of the composition of the bulk solvents, the additives, the concentration of the co- and counter-ions, the temperature, and the structures of the ampholytic analytes were investigated. The changes in standard enthalpy, Δ(ΔH°), entropy, Δ(ΔS°), and free energy, Δ(ΔG°), were calculated from the linear van't Hoff plots derived from the ln α vs 1/T curves in the studied temperature range (5-40°C). Unusual temperature behavior was observed on the ZWIX(-)™ column: decreased retention times were accompanied by increased separation factors with increasing temperature, and separation was entropically-driven. For the other three CSPs, enthalpically-driven enantioseparations were observed. Via the consequent determination of the elution order of the resolved enantiomers, the effects of the absolute configuration of the chiral anionic and cationic subunits of the zwitterionic CSPs could be elucidated. N-methylation of the amino acids led unexpectedly to a reversal of the elution sequence, which can be interpreted by a subtle shift of the hierarchical order of the sterically most important driving interaction sites from the cationic to the anionic units, and vice versa.
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: Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös u. 6, Hungary.
authors.forename: Enikő
authors.initials: E
authors.lastname: Forró
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 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
authors.affiliation: Department of Analytical Chemistry, University of Vienna, Währingerstrasse 38, 1090 Vienna, Austria. Electronic address: wolfgang.lindner@univie.ac.at.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lindner
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000838:Anions / Q000737:chemistry; D002412:Cations / Q000737:chemistry; D002623:Chemistry Techniques, Analytical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D011803:Quinine / Q000737:chemistry*; D013237:Stereoisomerism; D013451:Sulfonic Acids / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D000838:Anions; D002412:Cations; D013451:Sulfonic Acids; D011803:Quinine
keywords: Enantiomer separation; N(α)-methyl-protected cyclic β(3)-amino acids; Temperature effect; Zwitterionic chiral stationary phases