2. Enantiomer 1 interacts at three sites A•••A
0 , B•••B
0 and C•••C
0 , whereas its mirror
image, enantiomer 2, does not interact at site C•••C
0 . If the C•••C
0 interaction
results in the stabilisation of the transient diastereomeric complex between
enantiomer 1 and the CSP.
3. Consequently, enantiomer 1 will be retained on the column longer than
enantiomer 2.
However, a destabilising C•••C
0 interaction will reverse the elution order, that is,
enantiomer 1 will be eluted before enantiomer 2. If the C•••C
0 interaction is minimal
or non-existent, chiral recognition will not occur and the racemate will not be
resolved. The three-point model suggests that at least three attractive interactions
between the receptor or chiral selector and one of the enantiomers of the racemate
need to be possible to obtain enantioselectivity. At least one interaction must depend
on the stereochemistry at the chiral centre of both receptor and the enantiomer.
Otherwise unfavourable associations might be formed.
Wainer identified five types (I–V) of CSPs which are still used for characterisation of CSPs and the corresponding enantiomer-selective mode of action (Wainer
et al. 1986; Lough 2014) (Table 3.1).
However, both scientists and producers struggle until today to characterise the
multitude of CSPs developed during the past years according to the above scheme
(Lough 2014). In parallel to Wainer’s classification, other authors also attempted to
develop a useful classification system for CSPs. Taylor and Maher suggested another
classification (Taylor and Maher 1992), obviously inspired and, thus, quite similar to
Wainer’s recommendations:
• Type 1: The solute is part of a diastereomeric metal complex (enantioselective
ligand-exchange chromatography (LEC). This is a special case of ion exchange
and involves the reversible formation of a metal complex by coordination of
substrates that can act as ligands to the metal ion; it has wider application than the
resolution of racemates. For further details, the reader should refer to the studies
by Schmid et al. (2001), Remelli (2017) and Hyun (2018).
• Type 2: Essentially the only discernible interactions are attractive charge-transfer
interactions. Pioneering studies were earlier carried out by a team in Israel led by
Gil-Av (Charles et al. 1975; Gil-av 1975; Hare and Gil-Av 1979), who used
Table 3.1 Wainer’s type of CSP classification (references above)
Type Classification
Examples
I
Formation of complexes based on attractive interactions Pirkle-type CSPs
II
Combination of attractive interactions and inclusion
complexes
Cellulose-based CSP
III
Chiral cavities forming inclusion complexes
Cyclodextrin, crown-etherbased CSP
IV
Diastereomeric metal complexes
Chiral ligand-exchange CSP
V
Protein base CSP; combination of hydrophobic and
polar interactions
α-acid glycoproteins
3.5 The Evolution of Chiral Stationary Phases for Liquid Chromatography
39
0 , B•••B
0 and C•••C
0 , whereas its mirror
image, enantiomer 2, does not interact at site C•••C
0 . If the C•••C
0 interaction
results in the stabilisation of the transient diastereomeric complex between
enantiomer 1 and the CSP.
3. Consequently, enantiomer 1 will be retained on the column longer than
enantiomer 2.
However, a destabilising C•••C
0 interaction will reverse the elution order, that is,
enantiomer 1 will be eluted before enantiomer 2. If the C•••C
0 interaction is minimal
or non-existent, chiral recognition will not occur and the racemate will not be
resolved. The three-point model suggests that at least three attractive interactions
between the receptor or chiral selector and one of the enantiomers of the racemate
need to be possible to obtain enantioselectivity. At least one interaction must depend
on the stereochemistry at the chiral centre of both receptor and the enantiomer.
Otherwise unfavourable associations might be formed.
Wainer identified five types (I–V) of CSPs which are still used for characterisation of CSPs and the corresponding enantiomer-selective mode of action (Wainer
et al. 1986; Lough 2014) (Table 3.1).
However, both scientists and producers struggle until today to characterise the
multitude of CSPs developed during the past years according to the above scheme
(Lough 2014). In parallel to Wainer’s classification, other authors also attempted to
develop a useful classification system for CSPs. Taylor and Maher suggested another
classification (Taylor and Maher 1992), obviously inspired and, thus, quite similar to
Wainer’s recommendations:
• Type 1: The solute is part of a diastereomeric metal complex (enantioselective
ligand-exchange chromatography (LEC). This is a special case of ion exchange
and involves the reversible formation of a metal complex by coordination of
substrates that can act as ligands to the metal ion; it has wider application than the
resolution of racemates. For further details, the reader should refer to the studies
by Schmid et al. (2001), Remelli (2017) and Hyun (2018).
• Type 2: Essentially the only discernible interactions are attractive charge-transfer
interactions. Pioneering studies were earlier carried out by a team in Israel led by
Gil-Av (Charles et al. 1975; Gil-av 1975; Hare and Gil-Av 1979), who used
Table 3.1 Wainer’s type of CSP classification (references above)
Type Classification
Examples
I
Formation of complexes based on attractive interactions Pirkle-type CSPs
II
Combination of attractive interactions and inclusion
complexes
Cellulose-based CSP
III
Chiral cavities forming inclusion complexes
Cyclodextrin, crown-etherbased CSP
IV
Diastereomeric metal complexes
Chiral ligand-exchange CSP
V
Protein base CSP; combination of hydrophobic and
polar interactions
α-acid glycoproteins
3.5 The Evolution of Chiral Stationary Phases for Liquid Chromatography
39