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 β-amino acid enantiomers as ampholytic model compounds

Abstract

In a systematic way enantioseparations of non-methylated and the corresponding N-monomethylated ampholytic cyclic ß-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.

Liquid chromatographic enantioseparation of limonene‐based carbocyclic β‐amino acids on zwitterionic Cinchona alkaloid‐based chiral stationary phases

“…The data obtained on ZWIX columns revealed that, in general, an increasing counterion concentration resulted in reduced retention factors, as expected for ion‐exchangers. The slopes of the log k versus log c plots in this study (0.25–0.31) are in accordance with our results obtained on ZWIX phases working in zwitterionic mode . However, ZWIX phases working in a “uni‐ionic” mode as anion‐exchanger or cation‐exchanger exhibited steeper slopes (0.6–1.0).…”

Comparative study on the liquid chromatographic enantioseparation of cyclic β‐amino acids and the related cyclic β‐aminohydroxamic acids on Cinchona alkaloid‐based zwitterionic chiral stationary phases

“…It is interesting to note that the slopes of the log k versus log c plots were changed in a very narrow range, between −0.20 and −0.30 for all the SAs studied, in accordance with slopes obtained for zwitterionic columns working in zwitterionic mode . The amino acids is expected to have zwitterionic character, and able to bind to the SO through the formation of double ion‐pairs.…”

“…Under the studied conditions, practically identical slopes were obtained for each enantiomer on all four CSPs, thus the individual enantioselectivity characteristics remained almost constant when the counter-ion concentration changed. It is interesting to note that the slopes of the log k versus log c plots were changed in a very narrow range, between −0.20 and −0.30 for all the SAs studied, in accordance with slopes obtained for zwitterionic columns working in zwitterionic mode [22,35]. The amino acids is expected to have zwitterionic character, and able to bind to the SO through the formation of double ion-pairs.…”

Enantiomeric analysis of simendan on polysaccharide‐based stationary phases by polar organic solvent chromatography

“…The plot of ln α versus 1/T was linear ( r 2 > 0.97), meaning that the conformation of the chiral selectors remains essentially invariant at 15–40°C [35]. The calculated values of and were negative with ACN as the mobile phase, indicating that the separation process was controlled by enthalpy [36]. However, relatively small positive values were observed in the case of MeOH, accompanied by small absolute values of , indicating that the separation of enantiomers in MeOH was achieved by both enthalpic and entropic contributions.…”