Chiral brush-type

Pirkle,W. H., Murray, P. G. An instance of temperature-dependent elution order of enantiomers from a chiral brush-type HPLC column,/. High Res. Chromatogr., 1993,16, 285-288. 

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... 

The high diffusivity and low viscosity of sub- and supercritical fluids make them particularly attractive eluents for enantiomeric separations. Mourier et al. first exploited sub- and supercritical eluents for the separation of phosphine oxides on a brush-type chiral stationary phase [28]. They compared analysis time and resolution per unit time for separations performed by LC and SFC. Although selectivity (a) was comparable in LC and SFC for the compounds studied, resolution was consistently... 

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]. 

An understanding of the recognition of chirality at a molecular level has become of interest in many fields of chemistry and biology. In the past decade, many attempts to clarify the mechanism of chiral recognition on CSPs for liquid chromatography have been made by means of chromatography, NMR spectroscopy,199 202 X-ray analysis, and computational methods.203 - 206 The successful studies have been mostly carried out for the small-molecule CSPs, especially cyclodextrin-based CSPs and Pirkle-type (brush-type) CSPs. In contrast, only a few mechanistic studies on chiral discrimination at the molecular... 

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.)... 

Brush-type, proteins, CDs, natural molecular imprint-based polymers (MIP), and macrocyclic antibiotics have been immobilized as chiral selectors on packed-CEC columns. Zheng and Shamsi demonstrated the possibility of using chiral CEC—ESI/MS with a commercially packed column for the determination of warfarin enantiomers in human plasma using coumachlor as an internal standard (IS). Robustness of this chiral CEC capillary was recently improved by a novel procedure and applied for the simultaneous enantiosepara-tion of height /1-blockers with multimodal CSP using different combinations of vancomycin and teicoplanin, as presented in Figure 5. ... 

Silica Modified in a Brush-Type Manner with Chiral Molecules... 

Figure 13. Schematic view of brush-type CSPs showing the chiral selector substituents oriented towards the liquid phase. Solvent molecules and the respective solvation are not shown. Stereoselective [SO-SA] interactions, attractive or repulsive, are located invariably within the heterogeneously structured chiral stationary phase.

The most successful and broadly applied chiral stationary phases comprise the cellu-lose-and amylose-based phases developed by Okamoto (Chiracel and Chiralpak) (39), brush-type phases developed by Pirkle (40),... 

Mechanistic considerations (e.g., the extensive work published on brush-type phases) or the practitioner s experience might help to select a chiral stationary phase (CSP) for initial work. Scouting for the best CSP/mobile phase combination can be automated by using automated solvent and column switching. More than 100 different CSPs have been reported in the literature to date. Stationary phases for chiral pSFC have been prepared from the chiral pool by modifying small molecules, like amino acids or alkaloids, by the deriva-tization of polymers such as carbohydrates, or by bonding of macrocycles. Also, synthetic selectors such as the brush-type ( Pirkle ) phases, helical poly(meth) acrylates, polysiloxanes and polysiloxane copolymers, and chiral selectors physically coated onto graphite surfaces have been used as stationary phases. 

Modified-C02 mobile phases excel at stereochemical separations, more often than not outperforming traditional HPLC mobile phases. For the separation of diastereomers, silica, diol-bonded silica, graphitic carbon, and chiral stationary phases have all been successfully employed. For enantiomer separations, the derivatized polysaccharide, silica-based Chiralcel and Chiralpak chiral stationary phases (CSPs) have been most used, with many applications, particularly in pharmaceutical analysis, readily found in the recent literature (reviewed in Refs. 1 and 2). To a lesser extent, applications employing Pirkle brush-type, cyclodextrin and antibiotic CSPs have also been described. In addi-... 

With chromatographic production processes the elution order of the enantiomers is of importance. In SMB processes the raffinate enantiomer can often be obtained with better economics as it is recovered at higher purities and concentrations. If the CSP offers the possibility of choosing one of the two optically active forms of the selector, the adsorbent on which the desired enantiomer elutes first should be chosen. This option can be used especially with the brush-type phases with monomolec-ular chiral selectors. Even if the CSP is not available in both forms, the elution order should be checked carefully as the elution order might be reversed on two very similar adsorbents or with two similar mobile phase combinations. Okamoto (1991) and Dingenen (1994) have shown that by changing only from 1-propanol to 2-propanol, respectively with 1-butanol, the elution order on a cellulose-based CSP might reverse. 

The brush-type of CSP was introduced by Pirkle who was one of the pioneers of modern enantioselective liquid chromatography [55]. The most frequently used 7i-acceptor phases are derived from the amino acids phenylglycine (DNBPG) (Fig. 6.8) or leucine (DNBLeu) covalently or ionically bonded to 3-aminopropyl silica gel [56, 57]. These CSPs are commercially available for analytical or preparative separation of enantiomers. Further CSPs based on amino acid or amine chiral selectors such as valine, phenylalanine, tyrosine [58] and l,2-tr s-diaminocyclohexane (DACH-DNB phase) [59] and 1,2-traus-diphenylethylene diamine (ULMO phase) [60] were also developed (Fig. 6.8). These CSPs have been applied for the preparative separation of the enantiomers of a few racemic compounds, but the number of reported preparative applications has remained very limited over the last 10 years. 

Laemmerhofer, M., Lindner,W. Quinine and quinidine derivatives as chiral selectors. I. Brush type chiral stationary phases for high-performance liquid chromatography based on cinchonan carbamates and their application as chiral anion exchangers, J. Chromatogr. A, 1996, 741, 33-48. 

Lipkowitz, K.B.,Theoretical studies of brush-type chiral stationary phases,... 

Other types of CSPs, known as brush type, have been constructed synthetically. A chiral structure, usually an amide, is linked to silica by a tether molecule. This approach has the potential for design of the chiral recognition elements. The ability to synthetically manipulate the structures also permits investigation of the role of specific structural elements in chiral selectivity. Several synthetic CSPs were developed by W. H. Pirkle and co-workers at the University of Illinois. An important example is the 3,5-dinitrobenzoyl (3,5-DNB) derivative of 7 -phenylglycine, which is attached to silica by aminopropyl tethers (CSP 2). The 3,5-DNB derivatives of several other amino acids (e.g., CSP 4) and diamines have also been explored. ... 

Pirkle or brush type bonded phases Helical chiral polymers (polysaccharides) Cyclodextrins and crown ethers Immobilised enzymes Amino acid metal complexes Three-point interaction Attractive hydrophobic bonding Host guest interaction within chiral cavity Chiral affinity Diastereomeric complexation... 

A special subclass of brush-type chiral stationary phases are the ion-exchange CSPs developed by Lammerhofer and Lindner (1996). By introducing an additional ionic moiety, a strong interaction between the selector and the selectand can be achieved. The first commercial available phases are based on the Cinchona alkaloids Quinine and Quinidine with an additional weak anion-exchange function offering good separation possibilities for chiral acids. A strong dependence of the capacity from the counter ion of the mobile phase could be demonstrated by Arnell (2009). 

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