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

Nóra Grecsó, Michal Kohout, Andrea Carotti, Roccaldo Sardella, Benedetto Natalini, F. Fülöp, Wolfgang Lindner, A. Péter, I. Ilisz

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)164-173
Number of pages10
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume124
DOIs
Publication statusPublished - May 30 2016

Fingerprint

Cinchona Alkaloids
Paroxetine
Enantiomers
Temperature
Molecular recognition
Organic acids
Thermodynamics
Phase composition
Computer Simulation
Acids

Keywords

  • Enantiomer separation
  • High-performance liquid chromatography (HPLC)
  • Molecular dynamic simulations
  • Trans-Paroxetine enantiomers
  • Zwitterionic chiral stationary phases

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Spectroscopy
  • Clinical Biochemistry

Cite this

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. / Grecsó, Nóra; Kohout, Michal; Carotti, Andrea; Sardella, Roccaldo; Natalini, Benedetto; Fülöp, F.; Lindner, Wolfgang; Péter, A.; Ilisz, I.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 124, 30.05.2016, p. 164-173.

Research output: Contribution to journalArticle

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