Page 80 - Chiral Separation Techniques

56 3 Combinatorial Approaches to Recognition of Chirality: Preparation …

comparative biological testing [4]. Chromatographic separations continue to be used
for the process and quality controls, even after a large-scale asymmetric technology
had been developed and implemented.

3.2 Engineering of a Chiral Separation Medium

A chiral separation medium is a complex system. Ideally, interactions that lead to
enantioseparation are maximized while nonspecific interactions should be com-
pletely suppressed. Typically, a medium for chromatographic separations involves
the solid support, the selector, and the linker connecting the two, as shown in scheme
3-1.

Scheme 3-1

Most commercial CSPs contain chiral selectors (vide infra) supported by porous
silica beads. Silica-based chromatographic supports have numerous advantages such
as broad range of different porosities, high mechanical stability, and resistance to
swelling. Columns packed with these materials generally exhibit high efficiencies.
However, residual silanol groups on the surface of the silica may contribute to non-
specific interactions with the separated enantiomers, thereby decreasing the overall
selectivity of the separation medium. This was demonstrated by the improved enan-
tioselectivities measured for CSPs that had their residual silanol groups capped after
the attachment of a chiral selector [5]. In contrast to silica particles, synthetic organic
polymers are more seldom used as a platform for the preparation of chiral stationary
phases. Their excellent stability over the entire range of pH, the variety of available
chemistries, and the more accurate control of both the functionality and the porous
properties make them a good alternative to the well-established silica matrices.
Although porous polymer beads have been used successfully for a wide variety of
chromatographic separations including the size-exclusion chromatography of
synthetic polymers, the normal-phase or reversed-phase separations of small
molecules, and the ion-exchange and hydrophobic interaction chromatography of
biopolymers, there are only a few examples of polymer-based chiral separation
media with attached selectors [6–10]. In contrast, a larger number of chiral separa-
tions has been demonstrated using polymer-based molecular imprinted separation
media [5, 11–13].
The use of a polymeric support also affords a unique opportunity to control inde-
pendently the variables that may affect the chiral recognition process, which is hard
to achieve with silica. For example, the type and number of reactive sites can be eas-
ily adjusted with a polymer support. We recently reported an extensive study of the