Stationary phases cyclodextrins

In the initial experiments reported here we did not attempt to optimize the separation in terms of yield and production rate. Rather, cur intent was to demonstrate that displacement chromatographic separations are feasible on a chiral stationary phase, cyclodextrin-silica, and gather preliminary information regarding the structure of displacers which cam De used with cyclodextrin-sil icas. The method development sequence described in the previous paragraph will be followed in the discussion of the results. 

Chiral chromatography methods are considered by many to be superior to conventional methods in that, besides analytical applications, they offer the greatest potential for the preparation of optically pure forms of the isomers [5,27,28]. In these examples the third chiral species is an integral part of the LC (or GC) system and may appear as a plain stationary phase (cyclodextrins),... 

Chiral Stationary Phases for Gas Chromatography Small Molecule Stationary Phases Chiral Polysiloxane Stationary Phases Chiral Metal Chelating Stationary Phases Cyclodextrin Chiral Stationary Phases... 

Protein Based Stationary Phases The Pirkle Type Stationary Phases Coated Cellulose and Amylose Derivatives Macrocyclic Glycopeptide Stationary Phases Cyclodextrin Based Chiral Stationary Phases Synopsis References Chapter 9... 

Chromatography Online, Chrial-GC - Cyclodextrin chiral stationary phases from chrial gas chromatography, http //www.chromatography-online.org/Chrial-GC/Contemporary-Chiral-Stationary-Phases/Cyclodextrin.php. 

Chiral separation of flavonoids has also been carried out by chromatographic systems by using a chemically bonded chiral stationary phase or by the addition of chiral mobile phase additives (reviewed by Yanez et al. ). These chiral polymer phases can be further subdivided into polysaccharide-derived columns, and cyclodextrin and mixed cyclodextrin columns. With regard to chiral mobile phase additives, the addition of an optically active molecule to the mobile phase can facilitate separation of enantiomers on conventional stationary phases. Cyclodextrin as a chiral additive is widely used to separate enantiomers mainly by capillary electrophoresis (CE), as discussed in Section 3.6.2.I. Table 3.7 summarizes the most habitual HPLC procedures employed for the analysis of various classes of food flavonoids. 

Limitations with the chiral selectivity of the native cyclodextrins fostered the development of various functionalized cyclodextrin-based chiral stationary phases, including acetylated (82,83), sulfated (84), 2-hydroxypropyl (85), 3,5-dimethylphenylcarbamoylated (86) and... 

Gc chiral stationary phases can be broadly classified into three categories diamide, cyclodextrin, and metal complex. 

Gyclodextrins. As indicated previously, the native cyclodextrins, which are thermally stable, have been used extensively in Hquid chromatographic chiral separations, but their utihty in gc appHcations was hampered because their highly crystallinity and insolubiUty in most organic solvents made them difficult to formulate into a gc stationary phase. However, some functionali2ed cyclodextrins form viscous oils suitable for gc stationary-phase coatings and have been used either neat or diluted in a polysiloxane polymer as chiral stationary phases for gc (119). Some of the derivati2ed cyclodextrins which have been adapted to gc phases are 3-0-acetyl-2,6-di-0-pentyl, 3-0-butyryl-2,6-di-0-pentyl,... 

Although the chiral recognition mechanism of these cyclodexttin-based phases is not entirely understood, thermodynamic and column capacity studies indicate that the analytes may interact with the functionalized cyclodextrins by either associating with the outside or mouth of the cyclodextrin, or by forming a more traditional inclusion complex with the cyclodextrin (122). As in the case of the metal-complex chiral stationary phase, configuration assignment is generally not possible in the absence of pure chiral standards. 

Analytically, the inclusion phenomenon has been used in chromatography both for the separation of ions and molecules, in Hquid and gas phase (1,79,170,171). Peralkylated cyclodextrins enjoy high popularity as the active component of hplc and gc stationary phases efficient in the optical separation of chiral compounds (57,172). Chromatographic isotope separations have also been shown to occur with the help of Werner clathrates and crown complexes (79,173). 

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. 

Table 2. Retention Data for Racemic Compounds Separated on a p-Cyclodextrin Stationary Phase ...

It is in the study of this phenomenon where two-dimensional GC offers by far the most superior method of analysis. The use of chiral selector stationary phases, in particular modified cyclodextrin types, allows apolar primary and atropisomer selective secondary separation. Reported two-dimensional methods have been successful... 

Recently, multidimensional GC has been employed in enantioselective analysis by placing a chiral stationary phase such as a cyclodextrin in the second column. Typically, switching valves are used to heart-cut the appropriate portion of the separation from a non-chiral column into a chiral column. Heil et al. used a dual column system consisting of a non-chiral pre-column (30 m X 0.25 mm X 0.38 p.m, PS-268) and a chiral (30 m X 0.32 mm X 0.64 p.m, heptakis(2,3-di-(9-methyl-6-(9-tert-butyldimethylsilyl)-(3-cyclodextrin) (TBDM-CD) analytical column to separate derivatized urinary organic acids that are indicative of metabolic diseases such as short bowel syndrome, phenylketonuria, tyrosinaemia, and others. They used a FID following the pre-column and an ion trap mass-selective detector following the... 

T. J. Ward, D. W. Armstrong, Cyclodextrin-stationary phases in Chromatographic chiral separations, M. Zief, L. J. Crane (Eds.), Chromatographic Science Series, Vol. 40, Marcel Dekker, New York (1988) Chapter 5. 

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. 

Mourier s report was quickly followed by successful enantiomeric resolutions on stationary phases bearing other types of chiral selectors, including native and deriva-tized cyclodextrins and derivatized polysaccharides. Many chiral compounds of pharmaceutical interest have now been resolved by packed column SFC, including antimalarials, (3-blockers, and antivirals. A summary is provided in Table 12-2. Most of the applications have utilized modified CO, as the eluent. 

In relation to separation of nucleotides, Hoffman61 found that adenine nucleotides interacted most strongly with cycloheptaamylose, presumably by inclusion of the base within the cavity of cyclodextrin. When epichlorohydrin-cross-linked cycloheptaamylose gel was used as a stationary phase for nucleic acid chromatography, adenine-containing compounds were retarded most strongly. 

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. 

Reaction conditions 0.1 g of the zeolite Y modified catalyst, tested in a conventional glass microreactor with racemic butan-2-ol (7.35 x 10" mol h-1), prevaporized in a nitrogen diluent (6.2 -6.7 x 10" mol h-1). Products were analyzed using on-line GC with a 40m capillary y- cyclodextrin colimm with trifluoroacetyl stationary phase, temperature programmed from 25-70 "C with a split ratio of 120 1. 

Early attempts to use cyclodextrins and their simple derivatives as chira stationary phases in gas chromatography met... 

There is a wide variety of commercially available chiral stationary phases and mobile phase additives.32 34 Preparative scale separations have been performed on the gram scale.32 Many stationary phases are based on chiral polymers such as cellulose or methacrylate, proteins such as human serum albumin or acid glycoprotein, Pirkle-type phases (often based on amino acids), or cyclodextrins. A typical application of a Pirkle phase column was the use of a N-(3,5-dinitrobenzyl)-a-amino phosphonate to synthesize several functionalized chiral stationary phases to separate enantiomers of... 

Terabe, S., Ozaki, H., Otsuka, K., and Ando, T., Electrokinetic chromatography with 2-O-carboxymethyl-P-cyclodextrin as a moving "stationary" phase, /. Ckromatogr., 332, 211, 1985. 

Lubda, D., Cabrera, K., Nakanishi, K., Lindner, W. (2003). Monolithic silica columns with chemically bonded b-cyclodextrin as a stationary phase for enantiomer separations of chiral pharmaceuticals. Anal. Bioanal. Chem. 377, 892-901. 

Because plasma and urine are both aqueous matrixes, reverse-phase or polar organic mode enantiomeric separations are usually preferred as these approaches usually requires less elaborate sample preparation. Protein-, cyclodextrin-, and macrocyclic glycopeptide-based chiral stationary phases are the most commonly employed CSPs in the reverse phase mode. Also reverse phase and polar organic mode are more compatible mobile phases for mass spectrometers using electrospray ionization. Normal phase enantiomeric separations require more sample preparation (usually with at least one evaporation-to-dryness step). Therefore, normal phase CSPs are only used when a satisfactory enantiomeric separation cannot be obtained in reverse phase or polar organic mode. 

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