Page 83 - Chiral Separation Techniques

3.3 Chiral Selectors 59

mid-1970s [6]. These highly selective and stable selectors have found only a lim-
ited application for the separation of atropoisomers. In contrast, modified cyclic
glucose oligomers – cyclodextrins – have proven to be very universal chiral selec-
tors for chiral separations in electrophoresis, gas chromatography, and liquid
chromatography [26]. In addition to the formation of reversible stereoselective
inclusion complexes with the hydrophobic moieties of the solute molecules that
fit well into their cavity, they are often functionalized to further enhance hydro-
gen bonding and dipolar interactions [27]. Attached covalently to porous silica
beads, they afford very robust CSPs with modest selectivities for a number of
racemates.
6. Metal ion complexes. These “classic” CSPs were developed independently by
Davankov and Bernauer in the late 1960s. In a typical implementation, copper (II)
is complexed with L-proline moieties bound to the surface of a porous polymer
support such as a Merrifield resin [28–30]. They only separate well a limited num-
ber of racemates such as amino acids, amino alcohols, and hydroxyacids.
7. Small chiral molecules. These CSPs were introduced by Pirkle about two decades
ago [31, 32]. The original “brush”-phases included selectors that contained a chi-
ral amino acid moiety carrying aromatic π-electron acceptor or π-electron donor
functionality attached to porous silica beads. In addition to the amino acids, a
large variety of other chiral scaffolds such as 1,2-disubstituted cyclohexanes [33]
and cinchona alkaloids [34] have also been used for the preparation of various
brush CSPs.

3.3.1 Design of New Chiral Selectors

CSPs with optically active polymers, such as modified cellulose, polyacrylates, and
proteins, have been used successfully for a variety of enantioseparations [5, 13, 15,
17]. Despite extended studies, the mechanism of separation for these CSPs is not yet
completely understood, which makes it difficult to develop new media of this type.
In contrast, bonded natural and synthetic chiral selectors such as substituted
cyclodextrins, crown ethers, and brush-type selectors have several advantages
including well-defined molecular structures and sufficiently developed enantiomer
“recognition” models. For example, the separation of enantiomers with brush-type
stationary phases is based on the formation of diastereoisomeric adsorbate “com-
plexes” between the analyte and the selector. According to the Dalgliesh’s 3-point
model [35], enantiomer recognition is achieved as a result of three simultaneous
attractive interactions (donor – acceptor interactions such as hydrogen bonding, π-
stacking, dipole – dipole interactions, etc.) between the selector and one of the enan-
tiomers being separated. At least one of these interactions must be stereochemically
dependent [36–39]. Compared to all other selectors, brush-type systems afford the
most flexibility for the planned development of a variety of different chiral station-
ary phases suitable for the separation of a broad range of analyte types [40, 41].
The majority of the original chiral selectors for brush-type CSPs were derived
from natural chiral compounds. Selectors prepared from amino acids, such as phenyl