Page 84 - Chiral Separation Techniques

60 3 Combinatorial Approaches to Recognition of Chirality: Preparation …

glycine and leucine, [42–45] and quinine [46, 47], are just a few examples of the
most common chiral moieties. However, further development of highly selective
CSPs requires the design of new types of synthetic receptors that will also make use
of compounds outside the pool of natural chiral building blocks.

3.4 In Pursuit of High Selectivity

According to Equation 3, the resolution R of two peaks in column separation is con-
s
trolled by three major variables: retention defined in terms of the retention factor k ;
column efficiency expressed as the number of theoretical plates N; and selectivity
characterized by the selectivity factor α [48]:

R = N (α −1) k (3)
l
s +
4 1 k
l
In this equation, k is the retention factor of the first peak. The most significant con-
1
tribution to the overall resolution has the selectivity term (α – 1) since the resolution
is a linear function of the selectivity factor. Obviously, an excellent separation can
also be achieved on columns with a high efficiency. However, the dependency of res-
olution on efficiency is not linear, and levels off at high efficiencies thus making the
quest for a further increase less useful. Since the technology of packed analytical
columns is well established and columns with very high efficiencies can be pro-
duced, baseline enantioseparations are achieved even with selectors that have low
selectivity factors α close to 1. This is why many commercial columns are very suc-
cessful despite their modest selectivity factors for most racemates that typically do
not exceed α = 3. In fact, very high selectivity factors are often not desirable for ana-
lytical separations since the second peak would elute much later and the time
required for the separation would be extended unnecessarily [49]. A highly desirable
feature for chiral columns is their broad selectivity, i.e. their ability to separate a
large number of various enantiomers.
Most of the criteria and features outlined above for liquid chromatography media
also apply to the development of selectors for electrodriven separations such as elec-
trophoresis and electrochromatography.
Chromatographic separations in preparative columns and on preparative and pro-
cess scale are based on the same concepts. However, packing large-scale columns to
achieve efficiencies matching those of analytical columns remains a serious chal-
lenge. Typically, preparative columns have much lower efficiencies even if they are
packed with analytical grades of stationary phases. Therefore, preparative columns
have to be much longer in order to obtain the same number of theoretical plates that
enable separations similar to those achieved in smaller columns. Unfortunately, the
use of longer columns substantially contributes to the costs of the equipment, and