Page 315 - Chiral Separation Techniques

12.4 Chiral Stationary Phases in SFC 307

12.4 Chiral Stationary Phases in SFC

The low polarity of CO -based eluents makes SFC a normal phase technique.
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Therefore, it is not surprising that most of the successful applications of chiral SFC
have utilized CSPs designed for normal phase LC. However, some exceptions have
been noted. Specific applications of various CSPs are outlined in the next sections.

12.4.1 Brush-type

The brush-type (Pirkle-type) CSPs have been used predominantly under normal
phase conditions in LC. The chiral selector typically incorporates π-acidic and/or π-
basic functionality, and the chiral interactions between the analyte and the CSP
include dipole–dipole interactions, π–π interactions, hydrogen bonding, and steric
hindrance. The concept of reciprocity has been used to facilitate the rational design
of chiral selectors having the desired selectivity [45].
As noted earlier, the first report of chiral packed column SFC utilized a brush-type
CSP for the separation of phosphine oxides [28]. The CSP consisted of (R)-N-(3,5-
dinitrobenzoyl)phenylglycine covalently bonded to aminopropyl silica. Macaudière
and co-workers resolved a series of aromatic amides on the same type of CSP. They
postulated that the chiral recognition mechanisms were identical in SFC and LC, and
that the methods were interchangeable [46]. Their results contrast significantly with
the observations of Siret et al. for a CSP based on a tyrosine derivative (ChyRoSine-
A) [47]. Enantioseparation of β-blockers was achieved on the ChyRoSine-A CSP
with a modified CO eluent in SFC, but the same compounds were not resolved in
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LC. Modeling studies have suggested that CO interacts with solutes having certain
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structural features to enhance chiral recognition in SFC [48]. A short (5 cm) column
packed with ChyRoSine-A yielded separations of β-blocker enantiomers in less than
2 min [49].
A new brush-type CSP, the Whelk-O 1, was used by Blum et al. for the analytical
and preparative-scale separations of racemic pharmaceutical compounds, including
verapamil and ketoprofen. A comparison of LC and SFC revealed the superiority of
SFC in terms of efficiency and speed of method development [50]. The Whelk-O 1
selector and its homologues have also been incorporated into polysiloxanes. The
resulting polymers were coated on silica and thermally immobilized. Higher effi-
ciencies were observed when these CSPs were used with sub- and supercritical flu-
ids as eluents, and a greater number of compounds were resolved in SFC compared
to LC. Compounds such as flurbiprofen, warfarin, and benzoin were enantioresolved
with a modified CO eluent [37].
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