Contributions to the theory and practice of the chromatographic separation of enantiomers

Abstract

The theory and practice of enantioselective capillary chromatography employing metal coordination compounds and modified cyclodextrins as chiral stationary phases are treated. A unified approach involving all contemporary chromatographic methods and a single enantioselective column is described. Reliable thermodynamic data of enantioselectivity are derived by the retention-increment method. The existence of an isoenantioselective temperature is demonstrated. Kinetic enantiomerization studies are presented. The preparative-scale separation of enantiomers by gas chromatography with enantioselective packed columns is achieved. Unusual phenomena and future aspects of enantioselective chromatography are discussed.

Inductive and Mesomeric Effects of the [60]Fulleropyrrolidine Fragment and [60]Fullerene Sphere: A Quantitative Evaluation Based on Theory and Experiments

“…[5a, 9,10] For this purpose, the kinetic determination of the enantiomerization rate constant of 1 was performed by monitoring the racemization process of the pure enantiomers [enantiomeric excess (ee) values greater than 99. Table 2, clearly indicated the sensitivity of 1 to changes in configuration under quite mild conditions; this would be expected for strongly activated polarization of the C-H α bond.…”

A rational approach to predict and modulate stereolability of chiral α substituted ketones

“…Interconversions between enantiomeric atropisomers generally are characterized by moderate variations of standard free energy of activation (DG ] ðTÞ ), 7,[11][12][13][14][15][16][17][18][19][20][21][22][23] since these conformational processes do not involve r bond breakage. Conversely, enantiomerizations involving configurational inversion of tetracoordinate asymmetric atoms frequently show much higher DG ] ðTÞ barriers.…”

“…This evidence has led to an increased demand of chiral pharmaceuticals as pure enantiomers and more stringent guidelines for chiral analysis by regulatory authorities. [6][7][8] Therefore, drug manufacturers are bound to furnish extensive and unequivocal data concerning the stereochemical stability of chiral drugs that are administered in the enantiopure form. At the best of our knowledge, a rational procedure to select or design CaSKs endowed with a planned stereostability is not available at present, so that an evaluation of the configurational retention grade of the designed ketone is possible only at the end of study by direct experimental investigation.…”

Exploring enantioselective molecular recognition mechanisms with chemoinformatic techniques

“…In this context also polar effects, solvation effects and entropy differences are assumed to be equal for the diastereomeric complexations equilibria. Lipkowitz' and Schurig' reviews offer valid overviews on these aspects [8,99]. In any case, these approximations and assumptions can be reasonably generalized also for chemoinformatic approaches.…”

“…While several thermodynamic aspect should be taken into account when one wants to fully understand the mechanisms of chiral recognition with HPLC [99], most of the assumptions and approximations that are currently done with chemoinformatic techniques are also those applied in molecular modelling calculations. As an example, the chemoinformatic prediction of enantioselectivities assumes that absolute free energies are not computed, but rather determined as differential free energies.…”