packings designed exclusively for charge-transfer complexation. Their objective
was the resolution of helicene enantiomers, a particularly difficult objective in
that neither acidic nor basic functions are present on the asymmetric molecule to
assist with chiral recognition. Gil-Av’s team achieved the enantiomer resolution
of this chiral compound by bonding a chiral charge-transfer acceptor, tetranitrol9-fluorenylidene-amino-oxypropionic acid (TAPA) to aminopropylated silica
gel. Such packings as well as others, which have meanwhile been developed,
though they represent a pioneering achievement, were not general enough for
most applications. Charge-transfer complexation is also today used frequently for
enantiomer-selective separation (Del Rio et al. 2004; Blankenburg and Schmidt
2007; Mori and Inoue 2013; Shi et al. 2013; Wang et al. 2018). Multimodal,
multi-mechanistic chiral stationary phases that use both complexation and inclusion seem to be very widely applicable today.
• Type 3: The solute/CSP complexes are formed by multiple attractive interactions,
including hydrogen bonding, π–π interactions, dipole stacking etc. between the
solute and low-molecular weight CSP. These are often termed Pirkle-CSP, after
their principal inventor, or asymmetric strand CSP (Pirkle et al. 1984). During the
1980s, several groups reported generally useful packings in which relatively
simple structures containing just one or two centres of asymmetry are chemically
bonded to silica (Macaudiere et al. 1986; Pirkle and Burke 1991; Kato et al. 1998,
2001). This type of CSP is also termed variously “multiple interactions”, because
their organic groups are directed away from the silica network in a similar way as
the bristles of a brush. They are typically well-defined chemical structures, almost
always containing at least one of the following functions near the stereogenic
centre:
(I) A π-acidic or π-basic aromatic group, capable of donor–acceptor interactions (as in charge-transfer complexation)
(II) Polar hydrogen-bond donor/acceptor
(III) Dipolar bond, suitable for dipole–dipole interactions as in dipole stacking
(IV) Bulky nonpolar groups, providing a potential for steric repulsion, van der
Waals’s interaction and/or conformational control.
Evidently, the solutes to be separated must contain similar but complementary
groups, if favourable discrimination is to be achieved. Despite of the structural
simplicity of such CSPs, a very large number of analytes have been resolved on
those phases. Certainly, a very wide variety of types of analyte have proved to be
separable on such CSPs, including carbinols, hydantoins, lactams, succinimides,
phthalides, sulfoxides, and sulphides (Hou et al. 1997). If the analyte lacks all the
necessary interaction sites, it may be possible to overcome this problem by analyte
derivatisation, in this case using chiral reagents. Further appreciation of Type
3 phases including additional references covering this field is given in Gasparrini
et al. (2001) and Scriba (2016).
40
3 Enantiomer-Selective High- and Ultra- High-Performance Liquid Chromatography
was the resolution of helicene enantiomers, a particularly difficult objective in
that neither acidic nor basic functions are present on the asymmetric molecule to
assist with chiral recognition. Gil-Av’s team achieved the enantiomer resolution
of this chiral compound by bonding a chiral charge-transfer acceptor, tetranitrol9-fluorenylidene-amino-oxypropionic acid (TAPA) to aminopropylated silica
gel. Such packings as well as others, which have meanwhile been developed,
though they represent a pioneering achievement, were not general enough for
most applications. Charge-transfer complexation is also today used frequently for
enantiomer-selective separation (Del Rio et al. 2004; Blankenburg and Schmidt
2007; Mori and Inoue 2013; Shi et al. 2013; Wang et al. 2018). Multimodal,
multi-mechanistic chiral stationary phases that use both complexation and inclusion seem to be very widely applicable today.
• Type 3: The solute/CSP complexes are formed by multiple attractive interactions,
including hydrogen bonding, π–π interactions, dipole stacking etc. between the
solute and low-molecular weight CSP. These are often termed Pirkle-CSP, after
their principal inventor, or asymmetric strand CSP (Pirkle et al. 1984). During the
1980s, several groups reported generally useful packings in which relatively
simple structures containing just one or two centres of asymmetry are chemically
bonded to silica (Macaudiere et al. 1986; Pirkle and Burke 1991; Kato et al. 1998,
2001). This type of CSP is also termed variously “multiple interactions”, because
their organic groups are directed away from the silica network in a similar way as
the bristles of a brush. They are typically well-defined chemical structures, almost
always containing at least one of the following functions near the stereogenic
centre:
(I) A π-acidic or π-basic aromatic group, capable of donor–acceptor interactions (as in charge-transfer complexation)
(II) Polar hydrogen-bond donor/acceptor
(III) Dipolar bond, suitable for dipole–dipole interactions as in dipole stacking
(IV) Bulky nonpolar groups, providing a potential for steric repulsion, van der
Waals’s interaction and/or conformational control.
Evidently, the solutes to be separated must contain similar but complementary
groups, if favourable discrimination is to be achieved. Despite of the structural
simplicity of such CSPs, a very large number of analytes have been resolved on
those phases. Certainly, a very wide variety of types of analyte have proved to be
separable on such CSPs, including carbinols, hydantoins, lactams, succinimides,
phthalides, sulfoxides, and sulphides (Hou et al. 1997). If the analyte lacks all the
necessary interaction sites, it may be possible to overcome this problem by analyte
derivatisation, in this case using chiral reagents. Further appreciation of Type
3 phases including additional references covering this field is given in Gasparrini
et al. (2001) and Scriba (2016).
40
3 Enantiomer-Selective High- and Ultra- High-Performance Liquid Chromatography