achiral-chiral-coupled column systems. However, this switch cannot be performed
when operating a chiral column with traditional non-polar solvents, because they are
incompatible with aqueous, buffer-containing solvents.
• Type 5: The primary mechanism for the formation of a solute/CSP complex is
through attractive interactions, but inclusions also play an important role, because
these CSPs are high-molecular mass polymers. Some of these polymers essentially are of natural origins, such as those derived from cellulose and macrocyclic
antibiotics, and others, which are synthetic in origin, are mostly based upon
polyacrylates or methacrylates and polyacrylamides. Attempts to improve the
chromatographic and enantioselective properties of cellulose have concentrated
on derivatisation of its hydroxyl groups to decrease bulk polarity and to provide
additional bulk for interaction between CSP and analyte. Hesse and Hagel (Hesse
and Nagel 1973) prepared microcrystalline cellulose triacetate (CTA) and
observed that derivatisation of the hydroxyl groups did not destroy the helical
structure of cellulose, which retained its potential for chiral recognition as first
noted in the early experiments by Dalgliesh (1952) and others.
Mannschreck and co-workers (Lindner and Mannschreck 1980; Köller et al.
1983; Mintas et al. 1997) introduced microcrystalline CTA for HPLC separations
and, for example, resolved racemic compounds carrying aromatic groups. Certainly,
CTA can be used as a bulk packing, especially when cross-linked, but its pressure
resistance is limited to around 80 bar. A report by Rizzi (1990) claimed that its
usefulness can be improved significantly by coupling a swollen microcrystalline
CTA column with an achiral alkyl-silica column. The first successful commercial
packings of this type consisted of silica-supported cellulose triacetate. Its versatility
led Okamoto’s group to develop a range of such phases by changing the
derivatisation of cellulose (Okamoto et al. 1986). These CSPs, immobilised on
wide-pore silica gel, are marketed under the trade name Chiralcel
® (Sharp et al.
2006; Szaleniec et al. 2009; Plomley et al. 2011; Nakov et al. 2016; PrzejczowskaPomierny et al. 2017; Aboul-Enein et al. 2018). These CSPs can be used with mobile
phases such as pure ethanol and aqueous methanol and have successfully separated a
very wide range of analytes (Zuideveld et al. 2000; el-Hady et al. 2005; Beaufour
et al. 2006; Cirilli et al. 2009; Plomley et al. 2011). Although developed and
commercialised in Japan, they have been evaluated extensively in laboratories all
over the world, and many publications are based on investigations carried out with
these Type 5 phases. More details can be found in Taylor and Maher (1992), Toda
(2004), Mericko et al. (2007) and Ali et al. (2013).
Macrocyclic antibiotics/glycopeptides are a complex class of chiral selectors
applied to HPLC/UHPLC (Ward and Farris 2001; Ding et al. 2002; Dungelova
et al. 2003). Two types of glycopeptide-based chiral stationary phases were commercially available already in the early 2000s: vancomycin and teicoplanin. Today,
mainly four glycopeptides are used as CSPs: Ristocetin, teicoplanin, vancomycin
and teicoplanin aglycone (TAG) (Berthod 2009). The glycopeptide macrocyclic
chiral selectors appear to have broad applicability. They are multimodal chiral
stationary phases because they can be used effectively in the reversed-phase,
42
3 Enantiomer-Selective High- and Ultra- High-Performance Liquid Chromatography
when operating a chiral column with traditional non-polar solvents, because they are
incompatible with aqueous, buffer-containing solvents.
• Type 5: The primary mechanism for the formation of a solute/CSP complex is
through attractive interactions, but inclusions also play an important role, because
these CSPs are high-molecular mass polymers. Some of these polymers essentially are of natural origins, such as those derived from cellulose and macrocyclic
antibiotics, and others, which are synthetic in origin, are mostly based upon
polyacrylates or methacrylates and polyacrylamides. Attempts to improve the
chromatographic and enantioselective properties of cellulose have concentrated
on derivatisation of its hydroxyl groups to decrease bulk polarity and to provide
additional bulk for interaction between CSP and analyte. Hesse and Hagel (Hesse
and Nagel 1973) prepared microcrystalline cellulose triacetate (CTA) and
observed that derivatisation of the hydroxyl groups did not destroy the helical
structure of cellulose, which retained its potential for chiral recognition as first
noted in the early experiments by Dalgliesh (1952) and others.
Mannschreck and co-workers (Lindner and Mannschreck 1980; Köller et al.
1983; Mintas et al. 1997) introduced microcrystalline CTA for HPLC separations
and, for example, resolved racemic compounds carrying aromatic groups. Certainly,
CTA can be used as a bulk packing, especially when cross-linked, but its pressure
resistance is limited to around 80 bar. A report by Rizzi (1990) claimed that its
usefulness can be improved significantly by coupling a swollen microcrystalline
CTA column with an achiral alkyl-silica column. The first successful commercial
packings of this type consisted of silica-supported cellulose triacetate. Its versatility
led Okamoto’s group to develop a range of such phases by changing the
derivatisation of cellulose (Okamoto et al. 1986). These CSPs, immobilised on
wide-pore silica gel, are marketed under the trade name Chiralcel
® (Sharp et al.
2006; Szaleniec et al. 2009; Plomley et al. 2011; Nakov et al. 2016; PrzejczowskaPomierny et al. 2017; Aboul-Enein et al. 2018). These CSPs can be used with mobile
phases such as pure ethanol and aqueous methanol and have successfully separated a
very wide range of analytes (Zuideveld et al. 2000; el-Hady et al. 2005; Beaufour
et al. 2006; Cirilli et al. 2009; Plomley et al. 2011). Although developed and
commercialised in Japan, they have been evaluated extensively in laboratories all
over the world, and many publications are based on investigations carried out with
these Type 5 phases. More details can be found in Taylor and Maher (1992), Toda
(2004), Mericko et al. (2007) and Ali et al. (2013).
Macrocyclic antibiotics/glycopeptides are a complex class of chiral selectors
applied to HPLC/UHPLC (Ward and Farris 2001; Ding et al. 2002; Dungelova
et al. 2003). Two types of glycopeptide-based chiral stationary phases were commercially available already in the early 2000s: vancomycin and teicoplanin. Today,
mainly four glycopeptides are used as CSPs: Ristocetin, teicoplanin, vancomycin
and teicoplanin aglycone (TAG) (Berthod 2009). The glycopeptide macrocyclic
chiral selectors appear to have broad applicability. They are multimodal chiral
stationary phases because they can be used effectively in the reversed-phase,
42
3 Enantiomer-Selective High- and Ultra- High-Performance Liquid Chromatography