Cyclodextrin-bonded chiral stationary phase

Cyclodextrin stationary phases utilize cyclodextrins bound to a soHd support in such a way that the cyclodextrin is free to interact with solutes in solution. These bonded phases consist of cyclodextrin molecules linked to siUca gel by specific nonhydrolytic silane linkages (5,6). This stable cyclodextrin bonded phase is sold commercially under the trade name Cyclobond (Advanced Separation Technologies, Whippany, New Jersey). The vast majority of all reported hplc separations on CD-bonded phases utilize this media which was also the first chiral stationary phase (csp) developed for use in the reversed-phase mode. 

A. M. Stalcup, Cyclodextrin bonded chiral stationary phases in enantiomer separations in A practical approach to chiral separations by liquid chromatogra.phy, G. Subramanian, VCH, Weinheim (1994) Chapter 5. 

Many racemic mixtures can be separated by ordinary reverse phase columns by adding a suitable chiral reagent to the mobile phase. If the material is adsorbed strongly on the stationary phase then selectivity will reside in the stationary phase, if the reagent is predominantly in the mobile phase then the chiral selectivity will remain in the mobile phase. Examples of some suitable additives are camphor sulphonic acid (10) and quinine (11). Chiral selectivity can also be achieved by bonding chirally selective compounds to silica in much the same way as a reverse phase. A example of this type of chiral stationary phase is afforded by the cyclodextrins. 

The bonding of cyclodextrins to silica has provided a range of media known as chiral stationary phases (CSPs), which are capable of... 

Many types of chiral stationary phase are available. Pirkle columns contain a silica support with bonded aminopropyl groups used to bind a derivative of D-phenyl-glycine. These phases are relatively unstable and the selectivity coefficient is close to one. More recently, chiral separations have been performed on optically active resins or cyclodextrins (oligosaccharides) bonded to silica gel through a small hydrocarbon chain linker (Fig. 3.11). These cyclodextrins possess an internal cavity that is hydro-phobic while the external part is hydrophilic. These molecules allow the selective inclusion of a great variety of compounds that can form diastereoisomers at the surface of the chiral phase leading to reversible complexes. 

Common chiral stationary phases for gas chromatography have cyclodextrins bonded to a conventional polysiloxane stationary phase.7-8 Cyclodextrins are naturally occurring cyclic sugars. P-Cyclodextrin has a 0.78-nm-diameter opening into a chiral, hydrophobic cavity. The hydroxyls are capped with alkyl groups to decrease the polarity of the faces.9... 

Y. Gong and H. K. Lee, Application of Cyclam-Capped (5-Cyclodextrin-Bonded Silica Particles as a Chiral Stationary Phase in Capillary Electrochromatography for Enantiomeric Separations, Anal. Chem. 2003, 75,... 

Chiral stationary phase 138 Covalently attached /3-cyclodextrin bonded phase exploratory separations of PITC-, dansyl-, dabsyl-, and AQC-derivatized amino acids... 

The separation of enantiomers can be effected either by transforming them into diastereoisomers using a chiral reagent and separating them on conventional phases or by separating the enantiomers on chiral phases. The utilization of chiral phases has not yet become routine, but studies of enantiomeric dipeptides have been carried out (115,116). Pirkle et al. (117) and Hyun et al. (118) separated enantiomeric di- and tripeptides (methyl esters of /V-3-5-dinitrobenzoyl derivatives) on chiral stationary phases (CSPs) derived from (R)-a-arylalkylamines, (S)-N-(2-naphthyl) valine, or (S)-1 -(6,7-dimethyl-1 -naphthyl) isobutylamine. These workers were able to separate four peaks for each dipeptide derivative, corresponding to the two enantiomeric pairs (R,R)/(S,S) and (R,S)/(S,R). Cyclodextrin-bonded stationary phases and chiral stationary immobilized a-chymotrypsin phases were used to separate enantiomeric peptides (118a,b). 

Stalcup AM, Cyclodextrin bonded chiral stationary phases in enantiomer separations, in A Practical Approach to Chiral Separations by Liquid Chromatography (Subramanian G, Ed.), VCH Verlag, Weinheim, Germany, p. 95 (1994). 

Ruderisch, A., Pfeiffer, J., and Schurig, V. (2003) Mixed Chiral Stationary Phase Containing Modified Resorcinarene and Beta-Cyclodextrin Selectors Bonded to a Polysiloxane for Enantioselective Gas Chromatography,/. Chromatogr. 994, 127-135. 

Chang, S.C., Reid III, G.L., Chen, S., Chang, C.D., and Armstrong, D.W. (1993) Evaluation of a new polar-organic high-performance liquid chromatographic mobile phase for cyclodextrin-bonded chiral stationary phases, Trends in Anal. Chem. 12, 144-153. 

The above phases represent the most common phases used in solving nearly all of the frequently encountered application problems. There are many other stationary phases which are produced to tune the phase polarity for specific applications. In addition to these phases, there are liquid crystalline, chiral, cyclodextrin, polymers such as polystyrene, divinylben-zene, molecular sieves, and alumina, which are designed for specific separation problems. The chemistry of fused silica deactivation and stationary-phase application, bonding, and cross-linking has been reviewed in detail [3,4]. 

Y. Gong, Y. Xiang, B. Yue, G. Xue, J. S. Bradshaw, H. K. Lee, and M. L. Lee, Application of diaza-18-crown-6-capped (l-cyclodextrin bonded silica particles as chiral stationary phases for ultrahigh pressure capillary liquid chromatography, J. Chromatogr. A 1002 (2003), 63-70. 

The efficiency of chiral stationary phase (CSP) is crucial in chromatographic technique. Recently, a new p-cyclodextrin phenyl isocyanate bonded chiral stationary phase (CSP) was developed. This CSP is quite stable and can be used in most of HPLC solvents. Many drug enantiomers that do not have enantioseparation effect on native P-cyclodextrin column in reversed phase were separated very well on this new CSP. 

With chiral stationary phases, chromatographic separation of enantiomeric ferrocene derivatives is possible. An apparatus for the resolution of ferrocenyl alcohols and other compounds on triacetylcellulose has been described [60]. Analytical enantiomer separation of ferrocenyl alcohols, ethers, sulfides, and amines for the determination of enantiomeric excesses is best achieved on cyclodextrin bonded phases [61]. 

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-... 

These stationary phases separate enantiomers on the basis that one isomer fits in the pocket and the other does not. In this fashion, the relative speed of the isomers is different, and separation results. There are three main types of inclusion chiral stationary phases a-cyclodextrin, /Tcyclodextrin, and y-cyclodextrin. From these three native cyclodextrins, several derivations can be made to alter the selectivity of the inclusion complex, including formation of acetates, esters, and carbamates. Astec produces all three native cyclodextrin stationary phases as well as several derivatized phases (called the Cyclobond series), and as with their macrolide polypeptide phases, they are covalently bonded. 

Ruderisch, A, J Pfeiffer and V Schurig (2003). Mixed chiral stationary phase containing modified resorcinarene and yS-cyclodextrin selectors bonded to a polysiloxane for enantioselective gas chromatography. Journal of Chromatography A, 994(2), 127-135. 

The cyclodextrin based chiral stationary phases are some of the more popular materials used for contemporary chiral separations. One of their distinct advantages lies in their unrestricted and successful use with all types of solvent. In particular, they can be used very effectively in the reversed phase mode (a method of development that is not possible with some other chiral stationary phases) and, as well as being usable in a normal phase. They can also be used in the so-called polar organic mode, where the polar constituents of the mobile phase can be anhydrous diethylamine or glacial acetic acid, but in the complete absence of water. The cyclodextrins and their derivatives are widely used for all types of chiral separations, they have a good sample capacity, and can often be used for preparative separations. Cyclodextrin-based phases are readily available, usually covalently bonded to spherical silica gel particles 5 pm in diameter. There are numerous examples of the use of cyclodextrins in chiral separations and the following are some applications that illustrate their general use. 

C. Bertucci, E. Domenici, G. Uccello-Barretta and P. Salvador , High-Performance Liquid Chromatographic Resolution of Racemic l,4-benzodiazepin-2-ones by Means of a P-Cyclodextrin Silica Bonded Chiral Stationary Phase, J. Chromatogr., 506(1990)617. 

S.C. Chang, G.L. Reid III, S. Chen, C.D. Chang and D.W. Armstrong, Evaluation of a New Polar-Organic High-Performance Liquid Chromatographic Mobile Phase for Cyclodextrin-Bonded Chiral Stationary Phases, Trends in Anal. Chem., 12(4)0993)144. 

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