High-performance liquid chromatographic separation of unusual β3-amino acid enantiomers in different chromatographic modes on Cinchona alkaloid-based zwitterionic chiral stationary phases

Abstract

Polar-ionic and hydro-organic mobile phase mode of high-performance liquid chromatographic separations of 23 sterically constrained primary β(3)-amino acid enantiomers containing, alkyl, aryl or heteroaryl side-chains were carried out by using newly developed Cinchona alkaloid-based zwitterionic chiral selectors and the stationary phases Chiralpak ZWIX(+)™ and ZWIX(-)™. In the polar-ionic mode, the effects of the composition of the bulk solvent and the natures of the co- and counter-ions, while in the hydro-organic mode, the effects of the pH, the counter-ion concentration and the structures of the analytes were investigated. The separations of the enantiomers of these 23 primary β(3)-amino acids, which can be classified as a series of quasi- (pseudo-) homologs, were optimized in both chromatographic modes. The elution sequence was determined in most cases and a reversal of elution order on ZWIX(+)™ and ZWIX(-)™ column was observed. On the basis of this intermolecular recognition model between the selectors and the given enantiomers an indirect assignment of the resolved enantiomer via chromatography is proposed.

Quinine‐Based Zwitterionic Chiral Stationary Phase as a Complementary Tool for Peptide Analysis: Mobile Phase Effects on Enantio‐ and Stereoselectivity of Underivatized Oligopeptides

“…A molar acid‐to‐base ratio of 2:1 has been frequently found to be favorable. In general, however, the type of additives, acid‐to‐base ratio, and concentration of additives are instrumental factors for optimization of the overall chromatographic performance and may depend on amino acid residues in the peptide …”

“…In general, however, the type of additives, acid-to-base ratio, and concentration of additives are instrumental factors for optimization of the overall chromatographic performance and may depend on amino acid residues in the peptide. [25][26][27] Thereby, additives regulate the strength of the ionic interactions between selector and analyte molecules. They influence the solvation extent of both interaction partners (i.e., the formation of an ion-cloud around the charged sites and of a double layer of a particular thickness in dependence on the ionic strength on the charged surface, respectively) and act as displacers, which may result in a profound impact on the retention and the quality of the enantioseparation process 25,[28][29][30][31] .…”

Liquid and subcritical fluid chromatographic enantioseparation of Nα‐Fmoc proteinogenic amino acids on Quinidine‐based zwitterionic and anion‐exchanger type chiral stationary phases. A comparative study

“…The observed slopes around 0.29-0.36 correspond with the values of around 0.19-0.28 and 0.18-0.26 previously found for the ZWIX(+) system for the same SAs under LC 40 and SFC conditions 27 and for ß-amino acids in PIM. 41,42 The slight differences in the slopes obtained on ZWIX(−) for each enantiomer indicate that the enantioselectivity remained almost constant by varying the counterion concentration (data not shown).…”

Enantioseparation of racecadotril using polysaccharide‐type chiral stationary phases in polar organic mode

“…During chiral separations, temperature changes affect both analyte retention and enantioselective interactions . In order to obtain information about the mechanistic aspects of chiral discrimination process, the differences in the change of standard enthalpy Δ(ΔH°) and standard enthropy Δ(ΔS°) for the 2 enantiomers moving from the mobile to the stationary phase were calculated according to the modified van't Hoff equation: where R is the universal gas constant, T is the temperature, expressed in Kelvin, while α is the selectivity factor.…”