Pirkle-type CSPs phases

The brush-type (Pirkle-type) CSPs have been used predominantly under normal phase conditions in LC. The chiral selector typically incorporates tt-acidic and/or n-basic functionality, and the chiral interactions between the analyte and the CSP include dipole-dipole interactions, n-n 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]. 

Pirkle-type CSPs do not involve ionic interactions and therefore are almost exclusively operated in the normal-phase mode. The use of subcritical carbon dioxide based mobile phase, i.e., subcritical fluid... 

More recent developments in the field of the Pirkle-type CSPs are the mixed r-donor/ r-acceptor phases such as the Whelk-Of and the Whelk-02 phases.The Whelk-Of is useful for the separation of underiva-tized enantiomers from a number of families, including amides, epoxides, esters, ureas, carbamates, ethers, aziridines, phosphonates, aldehydes, ketones, carboxylic acids, alcohols and non-steroidal anti-inflammatory drugs.It has been used for the separation of warfarin, aryl-amides,aryl-epoxides and aryl-sulphoxides. The phase has broader applicability than the original Pirkle phases. The broad versatility observed on this phase compares with the polysaccharide-derived CSPs... 

New brush-type phases (donor-acceptor interactions) are appearing all the time. " Examples are stationary phases comprising quinine derivatives and trichloro-dicyanophenyl-L-a-amino acids as chiral selectors. Quinine carbamates, which are suitable for the separation of acidic molecules through an ionic interaction with the basic quinine group, are also commonly used but in general they are classified with the anion-exchange type of chiral selectors (see further) because of their interaction mechanism, even though r-donor, r-acceptor properties occur. (Some separations on Pirkle-type CSPs are shown in Table 2.)... 

SCHEME 1 Protocol for the development and optimization of mobile phases on Pirkle-type CSPs under the normal phase mode. AcOH, acetic acid TEA, triethylamine. 

Pirkle-type CSPs have achieved a good status in the field of the chiral resolution by liquid chromatography. In these phases, the chiral moiety on the silica support... 

A CSP consists of a chiral selector, which either alone constitutes the stationary phase or which has been immobilised to a solid phase. The chiral selector is a low molecular weight compound or a polymer, either synthetic or natural. A broad range of CSPs has been developed. Examples of CSPs that have been used successfully include polysaccharides, such as cellulose and its derivatives [6] and cyclodex-trins [7], and proteins, e.g. bovine serum albumin, aj-acid glycoprotein, cellulase, trypsin and a-chymotrypsin [8]. Several different synthetic polymers have also proven to be useful CSPs, for example the Blaschke-type CSPs (polyacrylamides and polymethacrylamides) [9] and the Pirkle-type CSPs [10]. 

The synthetic multiple-interaction or Pirkle-type class of CSP is not covered by patents in the same way that some other classes of CSP are. Accordingly researchers other than Pirkle s group have made Pirkle-type CSP worthy of commercialisation. Lindner has made tartramide coated phases, as well as derivatives [11], phases derived from cinchona alkaloids [12] utilising... 

Chiral resolution on Pirkle-type CSPs varies from one CSP to another and, therefore, it can be optimized by selecting a suitable chiral selector. Chiral resolutions on /r-acidic and -basic CSPs have been carried out under the normal phase mode. However, some reports are also available dealing with the use of reversed phase eluents, but the prolonged use of a reversed phase mobile phase is not recommended. With the development of more stable new CSPs, the use of the reversed mobile phase mode became possible. Nowadays, both mobile phase modes - that is, normal and reversed - are... 

The effect of the temperature is also important for chiral resolution on these CSPs. Pirkle etal. [81] reported inversion of the elution order when the temperature was changed from high to low and vice versa. The temperature effect observed was dependent on the content and polarity of the organic modifier in the mobile phase. The injection amount, the silica gel particle size, the spacer between the chiral selector and silica gel, and the column dimensions may be used as optimization parameters for chiral resolution. Recently, Baeyens et al. [80] carried out the chiral resolution of pirprofen on Whelk-Ol columns with internal diameters of 2.1 and 4.6 mm. The authors reported the best resolution on the 4.6 mm column (Figure 7.5). The optimization of chiral resolution on Pirkle-type CSPs is presented in Scheme 7.12. 

As discussed in Sect. 3.5, the interactions involved in the chiral recognition on Pirkle-type CSPs are mainly attractive forces, such as k-jt, hydrogen-bonding, and dipole-dipole interactions. Although bonded Pirkle-type CSPs have been used in reversed phase and polar nonaqueous mobile phase, most of the applications were found in normal-phase mode. With the introduction of SFC for the resolution of enantiomers [185], bonded Pirkle-type CSPs were among the most studied CSPs in the early application of chiral SFC [172, 175, 181, 186], Comparable enantioselectivity and the same elution order of enantiomers were usually observed for the enantioseparations of many compounds. Accordingly, similar chiral recognition mechanisms were believed to operate in both LC and SFC conditions [186]. However, when the enantioseparations of jt-acidic compounds on the n-acidic... 

In view of the importance of chiral resolution and the efficiency of liquid chromatographic methods, attempts are made to explain the art of chiral resolution by means of liquid chromatography. This book consists of an introduction followed by Chapters 2 to 8, which discuss resolution chiral stationary phases based on polysaccharides, cyclodextrins, macrocyclic glyco-peptide antibiotics, Pirkle types, proteins, ligand exchangers, and crown ethers. The applications of other miscellaneous types of CSP are covered in Chapter 9. However, the use of chiral mobile phase additives in the separation of enantiomers is discussed in Chapter 10. 

The Pirkle-type chiral stationary phases are quite stable and exhibit good chiral selectivities to a wide range of solute types. These CSPs are also popular for the separation of many drug enantiomers and for amino acid analysis. Primarily, direct chiral resolution of racemic compounds were achieved on these CSPs. However, in some cases, prederivatization of racemic compounds with achiral reagents is required. The applications of these phases are discussed considering re-acidic, re-basic, and re-acidic-basic types of CSP. These CSPs have also been found effective for the chiral resolution on a preparative scale. Generally, the normal phase mode was used for the chiral resolution on these phases. However, with the development of new and more stable phases, the reversed phase mode became popular. 

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