Stationary Phase Limitation by Chiral Selectivity

The amount of stationary phase available to an enantiomer that will permit adequate interaction in a chromatographic system will depend on how close it can approach the molecules of the stationary phase (i.e. it will depend on the stereochemistry of solute/phase system concerned). If both the solute and stationary phase are chiral in nature, one enantiomer of the solute may approach more closely to the stationary phase molecules and experience strong interactions, whereas, the other which may be more sterically alienated and, thus, have weaker interactions with the stationary phase. Although the first chiral separations in GC were obtained by Gil-Av et al. as long ago as 1966 (16), the use of GC for the separation of enantiomers took significantly longer before it was developed into a really practical system. This has been largely due to stationary phase instability resulting from the racemization of both the chiral stationary phase and the chiral solutes at elevated temperatures. Furthermore, at the elevated temperatures necessary to elute the solutes in a reasonable time, the chiral selectivity of the stationary phase can also be impaired.

It was not until 1977 that Frank, Nicholson and Bayer (17) produced a thermally stable chiral stationary phase by the co-polymerization of dimethylsiloxane with (2-carboxypropyl) methoxysilane and L-valine-t-butylamide. The material could be used up to 220^oC without significant racemization but, unfortunately, the product was not made commercially available until 1989. Today there are a number of extremely effective chiral stationary phases suitable for GC, some of the more successful being based on cyclodextrin, a material that will be described later. An example of the separation of the enantiomers of a a-halocarboxylic acid ester on a fused silica open tubular column coated with a b-cyclodextrin product is shown in figure 37.

Courtesy of ASTEC Inc.

Figure 37. The Separation of the Enantiomers of a-Halocarboxylic Acid Esters on a b-Cyclodextrin-Based Stationary Phase

The column was 10 m long and operated at 60^oC using nitrogen as the carrier gas. It is seen that an excellent, baseline separation was obtained for all the enantiomers