Chiral phases polysiloxane

The first chiral phases introduced for gas chromatography were either amino acid esters, dipeptide, diamide or carbonyl-bis(amino acid ester) phases [721,724,756-758]. In general, these phases exhitdted poor thermal stability and are infrequently used today. Real interest and progress in chiral separations resulted from the preparation of diamide phases grafted onto a polysiloxane backbone. These phases were thermally stable and could be used to prepare efficient open tubular columns [734,756,758-762]. These phases are prepared from commercially available poly(cyano-propylmethyldimethylsiloxanes) or poly (cyanopropylmethylphenyl-... 

The retention of the enantiomers in the column arises mainly from the equilibrium between the chiral selector selectand. A large excess of chiral additive causes the equilibrium to shift to the association side. An increase in the polarity of the medium decreases the strength of the hydrogen bonding between the selectand and the selector and shifts the equilibrium towards the dissociation side. Subsequently, the same selector was bound to a silica support and packed into an HPLC column it was also incorporated into a polysiloxane backbone and used as a chiral phase in gas chromatography in a similar manner previously used for Chirasil-Val [40,41]. 

The major breakthrough in the GC enantiomer separation has been the work of Bayer and associates [23,76], who synthesized a silicone-based chiral phase, stable up to 240°C. As shown in Fig. 3.14, a racemic mixture of 19 protein amino acids can be separated [23] on a glass capillary column coated with Chirasil-Val, a chiral polysiloxane phase. The phase was synthesized through coupling L-valine-tert-butylamide to a copolymer of dimethylsiloxane and carboxyalkylmethylsiloxane. 

Cyclodextrins (Alpha, Beta, and Gamma). Most of the earlier chiral phases have limited thermal stability. By chemically bonding a chiral stationary phase to a polysiloxane, the upper temperature limit can be extended. Chirasil-Val is perhaps the most famous stationary phase in this category. However, recent work has employed cyclodextrins as the key chiral recognition component in stationary... 

Gyclodextrins. As indicated previously, the native cyclodextrins, which are thermally stable, have been used extensively in Hquid chromatographic chiral separations, but their utihty in gc appHcations was hampered because their highly crystallinity and insolubiUty in most organic solvents made them difficult to formulate into a gc stationary phase. However, some functionali2ed cyclodextrins form viscous oils suitable for gc stationary-phase coatings and have been used either neat or diluted in a polysiloxane polymer as chiral stationary phases for gc (119). Some of the derivati2ed cyclodextrins which have been adapted to gc phases are 3-0-acetyl-2,6-di-0-pentyl, 3-0-butyryl-2,6-di-0-pentyl,... 

A number of ketones, pharmaceutical compounds, alcohols and hydroxy acids have also been resolved on this phase [724,765-767]. A chiral polysiloxane phase with tartramide substituents has been used for the separation of enantiomers capable of hydrogen bonding interactions with the stationary phase, such as enantiomers containing carboxylic, hydroxyl and amine functional groups [768]. 

The same is true for the chiral polysiloxanes described here. Their use as stationary phases in gas chromatography allows the calculation of the differences in enthalpy and entropy for the formation of the diaste-reomeric association complexes between chiral receptor and two enantiomers from relative retention time over a wide temperature range. Only the minute amounts of the polysiloxanes required for coating of a glas capillary are necessary for such determinations. From these numbers further conclusions are drawn on the stereochemical and environmental properties required for designing systems of high enantio-selectivity in condensed liquid systems. 

Another direct approach to chiral polymeric stationary phases is the modification of commercially available polysiloxanes which contain reactive side groups. Thus, the diamide phase was linked to a modified XE-60 polysiloxane phase (Table 2). In one case (XE-60-L-Val-(/ or 5)-a-pea)124 another center of stereogenicity (R or S configuration) has been introduced in the amide group. An XE-60-L-Val-(S)-x-pea column was used for the enantiomer separation of racemic. V-rert-butoxycarbonyl amino acids after their methylation with diazomethane (serine and threonine as the O-trimethylsilyl derivatives) (Figure 12)124. 

A limiting factor of complexation gas chromatography is the low temperature range (25-120°C). Therefore, improved thermostable polymeric stationary phases, e.g., Chirasil-Metal, in which the chiral metal chelates are chemically anchored to a polysiloxane backbone, have been prepared155 156. 

From our own experience, it should be emphasised that the enantioselectivity of modified cyclodextrin phases is considerably influenced by the polarity of the (non-chiral) polysiloxane solvents used. 

Using a chiral column, coated with a definite modified cyclodextrin as the chiral stationary phase, the elution orders of furanoid and pyranoid linalool oxides are not comparable [11, 12]. Consistently, the chromatographic behaviour of diastereomers and/or enantiomers on modified cyclodextrins is not predictable (Fig. 17.1, Table 17.1). Even by changing the non-chiral polysiloxane part of the chiral stationary phase used, the order of elution may significantly be changed [13]. The reliable assignment of the elution order in enantio-cGC implies the coinjection of structurally well defined references [11-13]. 

Common chiral stationary phases for gas chromatography have cyclodextrins bonded to a conventional polysiloxane stationary phase.7-8 Cyclodextrins are naturally occurring cyclic sugars. P-Cyclodextrin has a 0.78-nm-diameter opening into a chiral, hydrophobic cavity. The hydroxyls are capped with alkyl groups to decrease the polarity of the faces.9... 

Programmed temperature (120 -200°C) chiral separation on a 0.25-mm x 25-m open tubular column with a 0.25-nm-thick stationary phase containing 10 wt% fully methylated p-cyclodextrin chemically bonded to dimethyl polysiloxane. [From W. Vetter and W. Jun, Elucidation of a Polychlorinated Bipyrrole Structure Using Enantioselective GC," Anal. Chem. 3002, 74,4287.]... 

Modified cyclodextrins are the most versatile and widely used chiral stationary phases. The most widely used columns contain 10% to 50% cyclodextrin dissolved in either OV-101 or SE-52 polysiloxane. They are thermally stable up to 230°C but require some care in use because cyclodextrins are soluble in many solvents and can be washed off the column if they are exposed to too much solvent. Considerations in selecting a column... 

Since Pasteur separated crystalline sodium ammonium tartrate manually in 1848, many researchers have worked on the subject of enantiomeric separation. In 1939 Henderson and Rule fully separated derivatives of camphor by column chromatography using lactose as a stationary phase material [1]. Gil-Av et al. [2] were able to separate amino acid derivatives on a polysiloxane-based stationary phase by gas chromatography (GC) in 1966. Since then many approaches for a successful distinction between enantiomers have been developed for capillary GC and liquid chromatography [3]. It is still a current topic for researchers searching for chiral separation with SciFinder [4] results in 812 hits and searching for chiral recognition leads to 285 hits for the year 2003 only. 

Owing to the high thermal and long-term stability, amide phases bonded to polysiloxane are regarded as sensitive materials for the sensoric approach to enantiomeric separation. An important factor for the resolution of the stationary material is the number of dimethylpolysiloxane units between the chiral moieties. More than 200 different amide phases have been synthesised and applied for the discrimination of amino acids, lactate esters and many other substances [10]. 

In this chapter two different kinds of phase materials are presented the first is a chiral diamide selector bonded to a polysiloxane matrix the other selector system is a calix[4]arene with chiral residues which is attached to a polysiloxane backbone (Sect. 2.4). These systems were used in direct optical methods based on a change in the refractive index or the optical thickness of a transparent polymeric layer. 

Ruderisch, A., Pfeiffer, J., and Schurig, V. (2003) Mixed Chiral Stationary Phase Containing Modified Resorcinarene and Beta-Cyclodextrin Selectors Bonded to a Polysiloxane for Enantioselective Gas Chromatography,/. Chromatogr. 994, 127-135. 

There have been many reported chiral stationary phases for use in both packed and capillary gas chromatography. Most of these phases are of the carbonyl-bis-L-valine isopropyl ester, diamide, and peptide phase types. The most common phase is Chirasil-Val from Alltech Applied Science Laboratories (State College, PA). This phase is ideal for the separation of a variety of enantiomers including amino acids, sugars, amines, and peptides. The phase is composed of L-valine-tert-butylamide linked through a car-oxamide group to a polysiloxane backbone every seven dimethylsiloxane units apart. 

Chien and Cada [42] have prepared optically active and photoactive SCLC copolymers, 15, with the 4-alkoxyphenyl-4 -alkoxycinnamate chromophore, with the intention of creating LC polysiloxane networks that could be used to prepare macroscopically oriented organic ferroelectric polymers for electro-optical devices. Optical activity was introduced into the polymer by the use of a chiral spacer. Those copolymers which were mesogenic exhibited properties characteristic of a Sc. phase. UV-irradiation of thin films of the polymers in their mesomorphic states at 90°C, led to a loss of the IR absorption at 1635 cm-1 that is due to the cinnamate double bond, and to cross-linking. Long-term irradiation led to... 

This principle also governs the separation on the commercially available Chirasil-Val [37,38]. In Chirasil-Val , the chiral entity was incorporated in a polysiloxane backbone for higher thermal stability. Some of the compounds separated on Chirasil-Val contained only groups, such as V-TFA-proline esters, that are able to accept hydrogen bonding. To undergo such an interaction, the diamide phase has to have a conformation where both NH groups point toward the selectand in a conformation similar to the a-helix structure of proteins [36]. 

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