A wide variety of pharmaceuticals and other biologically active compounds have now been resolved on such columns and certain guidelines for mobile phase selection have emerged. Precolumn derivatization of amino acids with various fluorogenic reagents has led to new methods for chiral amino acid analysis using BSA-based columns in the final step.
Optimization of resolution and sensitivity can be based on a simple multivariate design. Examples show the use of three variables at most for the separation of cationic and anionic enantiomers. Further improvements of the chiral selectivity can be achieved by chiral anionic and cationic additives.
The effects indicate interactions with several sites, binding by cation-exchange and ion-pairing mechanisms. Peak symmetry and resolution can be improved by increased flow rate and considerable improvements have also been achieved by solvent and pH gradients. The results of these studies indicate that the observed stereoselectivity is a measure of the differences in binding affinities at two or more sites rather than the consequence of differential affinities at a single site.
The state of the art of chiral chromatographic resolution is briefly reviewed, with emphasis on the procedures introduced in the author's laboratory. This is followed by a discussion of proposed mechanisms of resolution in systems in which selectors and selectands interact by hydrogen bonding. Essentially, it is proposed that resolution models should be based on associates of the most stable conformations of both the stationary phase and the solute.
Data available from minimal energy computations and from hydrogen bonding modes in biological systems should be used for this purpose. This paper describes the liquid chromatographic separation of enantiomer by small bimolecular association, the driving force of which being the action of bidentate hydrogen bonds. This separation can be carried out by chiral mobile and stationary phases CSPs functionalized with chiral tartramide and amino acid diamides.
Many different enantiomers could be separated by hydrogen-bond association on CSPs derived from these components. The strategy for maximizing the separability of enantiomers, which is related to elimination of nondiscriminating interactions of CSPs, and the structure and thermodynamic features of diastereomeric hydrogen-bond associates are discussed in the following. Enantiomer separation was also possible in aqueous media when hydrogen bonding functionality was within a hydrophobic environment such as the liquid-solid interface in CSPs and micellar interior core.
Attention is directed to the hydrophobic features of interfacial phase and micellar hydrophobic core related to enantiomer separation. Increase in mobile phase strength of binary mobile phases, with racemic 3,5-dinitrobenzoyl phenyl ethyl amide as solute enantiomer pair, reduced retention but did not affect the selectivity of R -naphthyl R -NU or R -Phenyl R -PU- urea chiral stationary phases.
Gurus of Chiral Separations
Modifiers, methanol and acetonitrile, improved resolution but did not affect selectivity. With single-component mobile phases, selectivity was determined by the specific solvent while retention diminished with increase in solvent strength. Sterically hindered solutes showed reduced retention and selectivity.
R -NU showed much higher retention and selectivity than R -PU for all solute types and mobile phase compositions. Phenylalanine was less retained than alanine on both CSPs with all mobile phases, although their selectivity did not follow a fixed pattern. All amino acids were chromatographed as the 3,5-dinitrobenzoyl methyl esters. A direct, isocratic, sensitive and precise liquid chromatographic method is developed for the enantiomeric separation of aminoglutethimide AG and its acetylated metabolite AcAG using cellulose tris-3,5-dimethylphenyl carbamate Chiralcel OD column and cellulose tris- 4-methylphenyl beonzoate ester Chiralcel OJ column in series.
Chiral Separations by HPLC on Immobilized Polysaccharide Chiral Stationary Phases
The enantiomeric elution order is determined by chromatographing the racemate aminoglutethimide and racenate acetylated aminoglutethimide separately and their enantiomers under the similar conditions. In most cases chiral drug enantiomers have different biological and pharmacological activities due to different interactions on the receptors which also have chiral centers , posses.
Related Articles. Paper Title Pages. Resolution of clenbuterol hydrochloride enantiomers could be realized by alcohols such as ethanol, n-butanol, 2-butanol or tert- butanol together with acetonitrile, and propranolol hydrochloride enantiomers could only be resoluted by ethanol or n-butanol together with acetonitrile. The optical conditions of simultaneous resolution were obtained as follows: Under these conditions, R F value of resolution of clenbuterol hydrochloride enantiomers is 3.
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The two couples of enantiomers were all achieved base line separation. This chiral selector may be developed as chiral selector of CSP.
The detective wavelength was set at nm. Authors: Fei Rong, Ping Li. Abstract: Molecularly imprinted polymers MIPs of L-phenylalanine ethyl ester were synthesized in this study. Then, the prepared MIPs were packed in a stainless column and evaluated as the chiral stationary phases of high performance liquid chromatography HPLC. The MIPs exhibited a considerable capability of chiral separation between template molecule and its enantiomer with the separation factor of 1.
Furthermore, the weakest interaction model was introduced to study the chiral recognition mechanism of MIPs. The results suggested that the weakest interaction between the template molecule and the imprinted cavity played crucial role in chiral separation, and the molecular tension should be taken into consideration during the separation procedure.
Recent Advances in Chiral Separations | SpringerLink
The separation factor of 2. David M.
Goodall, David K. Lloyd, Zecai Wu. Chiral Separations by Thin-Layer Chromatography. Wilson, T. Spurway, L.
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- About this book.
- Recent Advances in Chiral Separations!
Witherow, R. Ruane, K. Back Matter Pages About this book Introduction This volume represents the proceedings of the second international meeting on chiral separations held at the University of Surrey between the 12th and 15th of September Like the preceding meeting, it was jointly organised by the Chromatographic Society and the Robens Institute of the University of Surrey in response to the continued interest in this area of separation science.
Of particular interest to the organisers was the very clear change in the nature of the delegates attending this second symposium as compared with the first. At the previous meeting the majority of the delegates were composed of chromatographers with problems in the area of chiral separations who were keen to learn as much as possible about these techniques from the handful of recognised experts in this area.