Empirical procedure that uses molecular structure to predict enantioselectivity of chiral stationary phases (original) (raw)
Related papers
Chiral recognition mechanisms in enantiomers separations: A general view
2010
The importance of chiral interactions for both preparative and analytical separations, particularly for pharmaceutical applications, is underlined by numerous publications in this field. Here, for the first time, a team of experienced analysts from industry and academe presents a comprehensive review of the various mechanisms that result in enantiomer separations. A better understanding of these processes is crucial for setting as well as improving chiral separation procedures and also for developing new applications. The coverage in this book includes a range of separation methods, such as gas, liquid, or countercurrent chromatography, and capillary electrophoresis. The special case of chiral ionic liquids is examined in detail. Most modern chiral selectors are discussed, including derivatized polysaccharide-and cyclodextrin-based selectors, along with a newly introduced class of carbohydrates: the cyclofructose selectors. This publication will be required reading not only for research and development departments in the pharmaceutical and cosmetic industries, but also for researchers in toxicology, environmental monitoring, and food research.
Separation of enantiomers with charged chiral selectors in CE
ELECTROPHORESIS, 2009
In this short overview the major developments in separation of enantiomers with charged chiral selectors are summarized in CE. The advantages of charged chiral selectors in comparison with their uncharged analogues are emphasized from the viewpoints of higher flexibility, higher and alternative separation selectivity, as well as alternative chiral recognition mechanism.
Chirality, 2005
The enantiodiscriminating potential of the weak anion exchange-type quinine-based chiral stationary phases (CSPs) for direct enantiomer separation of racemic 2-methoxy-2-(1-naphthyl)propionic acid (selectand, SA) was studied. The influence of structure variations of the selector (SO) in the carbamate functional group and/or in the C 6V position of quinoline moiety on retention and enantioselectivity was investigated. Systematic chromatographic studies were made to gain more insight into the overall chiral recognition mechanism for a given mobile phase. In this context, the tert-butylcarbamoyl quinine and the corresponding diisopropylphenyl-derived selector provided the highest resolution and enantioselectivity under polar-organic conditions with the elution order of (R) before the (S) enantiomer. When the bulkiness of the substituents in the C 6V position of the SO was increased, the selectivity was decreased in all cases. Alkylation of the nitrogen atom in the carbamate functionality of the SO resulted in the complete loss of enantiomer separation, confirming the crucial importance of the hydrogen-bond formation involved in the stereodiscriminating events. In addition, ten different mono-, bi-, or trivalent acids, necessary as competitor molecules (counter-ions) of the mobile phase, were screened to judge their influence on retention and overall enantioselectivity. Among them, acetic acid, formic acid, N-acetylglycine, and glycolic acid proved to be the most promising counter-ions with R s values of 6.35, 6.81, 8.19, and 7.34, respectively. On the basis of chromatographic data, a tentative molecular recognition model was proposed. Simultaneous ion-pairing and hydrogen bonding, in concert with pÀp stacking and steric interactions, were expected to be responsible for chiral recognition mechanism. This was partially corroborated by structural and/or conformational analysis of the tert-butylcarbamoyl quinine-2-methoxy-2-(1-naphthyl)propionic acid (SO-SA) complex. Chirality 17:S134-S142, 2005.
Analytica Chimica Acta, 2005
Chiral sulfoxide drugs such as omeprazole, lansoprazole and pantoprazole were chromatographed on three chiral stationary phases (CSP), using amylose tris-(phenylcarbamate) derivatives in the reversed-phase mode. The retention factors (k) and chromatographic partition coefficients (k w), obtained by extrapolation of the first according to the linear Snyder equation, were analyzed employing molecular interaction fields (MIF) of eluted analytes. Based on the generated MIF, chiral selectors could be identified for improving enantiomeric separation performance of the respective sulfoxides. The method is useful for predicting the complementarities between CSP and analytes, and thus to help the selection of appropriate stationary phases prior to their preparation.
Journal of Separation Science, 2002
The gas chromatographic separation of enantiomers of seven N-TFA-O-alkyl amino acid derivatives was studied on four different permethyl-and 2,6-di-O-methyl-3-Opentyl-b-and -c-CD stationary phases.It was shown that the separation of enantiomers N-TFA-O-alkyl amino acid derivatives depends both on the length of the linear alkyl chain attached to the stereogenic carbon (R 1 ) and to the ester part of the amino acid derivative (R 2 ). The cyclodextrin cavity size also affected selectivity. The separation of the amino acid derivatives decreases with increasing length of both the R 1 and R 2 alkyl chains on b-CD stationary phases, but improves on c-CD stationary phases. The separation of enantiomers of all N-TFA-O-methyl amino acid esters, is better on the larger c-cyclodextrin CSPs except for enantiomers of N-TFA-O-alkyl esters of alanine which are better separated on b-CD stationary phases.
Chirality, 2014
Prediction of chiral separation for a compound using a chiral selector is an interesting and debatable work. For this purpose, in this study 23 chiral basic drugs with different chemical structures were selected as model solutes and the influence of their chemical structures on the enantioseparation in the presence of maltodextrin (MD) as chiral selector was investigated. For chiral separation, a 100-mM phosphate buffer solution (pH 3.0) containing 10% (w/v) MD with dextrose equivalent (DE) of 4-7 as chiral selector at the temperature of 25°C and voltage of 20 kV was used. Under this condition, baseline separation was achieved for nine chiral compounds and partial separation was obtained for another six chiral compounds while no enantioseparation was obtained for the remaining eight compounds. The results showed that the existence of at least two aromatic rings or cycloalkanes and an oxygen or nitrogen atom or -CN group directly bonded to the chiral center are necessary for baseline separation. With the obtained results in this study, chiral separation of a chiral compound can be estimated with MD-modified capillary electrophoresis before analysis. This prediction will minimize the number of preliminary experiments required to resolve enantiomers and will save time and cost. Chirality 26:620-628, 2014.