Chromatography

Chiral GC (Part 1 of 2)

Chiral GC 1GC columns for enantiomer separation

Enantiomer separation is used for chiral substances which are non-superimposable mirror images of each other. Chromatography with chiral stationary phases allows separation of these enantiomers, which otherwise show identical physical and chemical properties. Chiral GC is the method of choice for the analysis of fragrances, flavors and other volatile substances while chiral HPLC is mainly used for the separation of pharmaceutically active ingredients.

This paper describes different stationary phases for Chiral Gas Chromatography based on modified cyclodextrins and their application for enantiomer separation of certain groups of substances.

History of chiral GC phases

In the 1960s Gil-Av [1] was the first to separate L- and D-amino acid esters using chiral stationary phases. In 1977, Frank, Nicholson and Bayer developed Chirasil-Val, a chiral phase bonded to polydimethylsiloxane [2]. Due to its relatively high temperature stability
of 200°C it could also be used for the separation of chiral compounds other than amino acids. Earlier phases had featured temperature limits of only 110 °C.

Further development during the late 1980s resulted in modified cyclodextrins as enantioselective stationary phases. Several working groups have studied synthesis and GC application of this group of substances [3,4,5]. Under the brand LIPODEX, MACHEREY-NAGEL has commercialized the phases developed by König [5,6]. They show a broad range of applications with temperature limits of 220 to 240 °C. One characteristic of LIPODEX phases are pentyl-substituted hydroxyls. Due to these substituents the selectors are oily liquids even at low temperatures. Schurig [7] had shown, that solid cyclodextrins can be used below their high melting point, if they are diluted with polysiloxanes. MACHEREY-NAGEL supplies these selectors with temperature limits up to 250 °C under the name HYDRODEX.

Additionally, metal-coordinated phases (Chirasil-Metal) [3] were developed in the late 1980s. In the 1990s, polysiloxanes with chiral crown ethers (Chirasil-Crown) [8] and chiral Calixarenes (Chirasil-Calix) [9] were established.

Modified cyclodextrin phasesCHIRAL GC 2

Cyclodextrin phases are among the most important chiral selectors in gas chromatography. Cyclodextrins are cyclic oligosaccharides consisting of six (α-cyclodextrin), seven (β-cyclodextrin), or eight (γ-cyclodextrin) glucose units bonded through α-1,4-linkages. Complete or partial alkylation and acylation result in numerous cyclodextrin derivatives with different enantioselectivity, which show good applicability as chiral stationary phases in gas chromatographic enantiomer analyses.

They allow separation of many types of substances including alcohols, diols, aldols, acetals, amino alcohols, alkyl halides, amines, barbiturates, carbohydrates, cyanhydrins, ketones, carboxylic acids, amino acids, hydroxycarboxylic acids, lactones, esters, alkenes and even alkanes. One advantage is that many compounds can be analyzed without derivatization. However, for certain substances the enantioselectivity can be enhanced by formation of derivatives (diastereomers).

Cyclodextrin phases diluted with polysiloxanes (HYDRODEX) and undiluted cyclodextrin phases (LIPODEX) are commercially available. For an overview of the different modifications see the summaries of HYDRODEX and LIPODEX phases, respectively.

The separation mechanism of modified cyclodextrin phases is determined by the interactions between the enantiomer and the stationary phase. These include the specific formation of hydrogen bonds, dipole/dipole, hydrophobic, and especially steric interactions with the enantiomers. Depending on the analyte and its molecular size, inclusion effects may also occur.

The selectivity of a phase is a function of the size of the cyclodextrin and the substitution pattern of the modification. However, a general prediction of a successful separation cannot be made from the separation mechanism. Even for structurally very similar compounds or for substances within a homologous series enantiodifferentiation can be very different.

 

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Chiral HPLC (Part 3 of 3)

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Chiral GC (Part 2 of 2)

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