Apparent and true enantioselectivity in enantioseparations

Abstract

The separation factor of two compounds in chromatography is the ratio of their equilibrium constants or retention factors. This parameter is universally employed to investigate their resolution and to optimize the experimental conditions of their analysis. In enantioseparations, the situation is more complex because there is a mixed retention mechanism. The retention factor is the sum of two contributions, one enantioselective, the other nonselective. Although both contribute to retention, the latter being identical for the two enantiomers and does not contribute to their separation. We show how these two contributions can be measured and how it becomes necessary to distinguish between the apparent, alpha(app), and the true, alpha(true), separation factors. The existence of nonselective sites is responsible for alpha(app) being less than alpha(true). Depending on the difference between these two factors, the more effective approach to improve a separation is either to increase the enantioselectivity or to reduce the nonselective interactions. Practical applications to separations of different beta-blockers on cellobiohydrolase are discussed. The apparent enantioselectivity of alprenolol is larger and increases faster with increasing pH than that of the more hydrophobic propranolol, in spite of the importance of hydrophobic interactions in the enantioselective mechanism. These two unexpected properties are discussed and explained.

Contributions to chromatographic chiral recognition of permethrinic acid stereoisomers by a quinine carbamate chiral selector: evidence from X-ray diffraction, DFT computations, 1H NMR, and thermodynamic studies

“…Yet, as so-called 'non-specific' interactions they may reduce the overall observed enantiodiscrimination level. 39 Thus, in our idealized view, the chiral distinction process of the present DIP-PCQN-SO between opposite enantiomers of the chiral cis-and trans-DCCA SA can be described by two equilibria for each pair of enantiomers (Eqs. 1a and 1b) wherein 1(S)-enantiomers have a higher affinity toward the SO and thus are more strongly retained.…”

“…3 from the respective van't Hoff plots. 43,44 Although such thermodynamic measurements do not pursue the highest level of complexity and differentiation because they neglect the surface heterogeneity with its distinct adsorption sites, 39,45,46 they are supposed to be valuable for interpretations and the comparison with DFT calculations. The results are summarized in Table 2.…”

“…At this point it should be emphasized that in general, both stereoselective and non-stereoselective adsorption processes may contribute to these net adsorption enthalpies and they have not been deconvoluted. 39,45,46 However, the overall dominating role of the specific ionic hydrogen bond is quite clear which may, under linear chromatography conditions, render non-specific adsorption processes at other binding sites than the SO rather negligible.…”

Exploring the molecular basis of the enantioselective binding of penicillin G acylase towards a series of 2-aryloxyalkanoic acids: A docking and molecular dynamics study

“…Since our ligands are negatively charged, we used a b value of 0.5 for the electrostatic interactions [56], and a a value of 0.181 for the non-polar interactions [57]. The constant parameter g 6 ¼ 0 can be adjusted by least-squares optimization in order to improve the calculated absolute binding energies quantitatively with respect to the experimental ones.…”

Chiral high‐performance liquid and supercritical fluid chromatographic enantioseparations of limonene‐based bicyclic aminoalcohols and aminodiols on polysaccharide‐based chiral stationary phases

“…In most cases in a given temperature range the ln α vs. 1/T dependence is linear. Achiral and chiral contributions to retention may play out to different degrees (Allenmark & Schurig, 1977;Chester & Coym, 2003;Gotmar, Fornstedt, & Guichon, 2000).…”