Cyclodextrin phases, preparation

Enantiomeric Stationary Phases. Chiral nonracemic chromatographic stationary phases prepared from p-cyclodextrin, derivatized with (R)- and (S)-NEI, and covalently bonded to a silica support are useful for the direct separation of enantiomers of a wide variety of compounds in both normal-phase and reversed-phase HPLC. ... 

Gorbatchuk VV, Gatiatulin AK, Ziganshin MA, Gubaidullin AT, Yakimova LS. Unusually high efficiency of (5-cyclodextrin clathrate preparation by water-free solid-phase guest exchange. J Phys ChemB 2013 117(46) 14544-56. 

Test performance To avoid difficulties early in the development of a chiral separation it is best to run the column test parameters before beginning work on a project. For cyclodextrin phases each of the phases has its own chiral standard for evaluation. See the manufacturer for details. Mobile phases are typically prepared based on volume ratios. The addition of salts is based on weight per volume. For salts compensation has to be made for water content. All salts, acids, and bases are reagent grade. Special care has to be given for the use of bases like triethylamine. Small sealed vials stored in the refrigerator are best. Air causes color oxidation and ghost... 

In this study, complexation of A9-THC and cannabidiol (prepared by freeze drying) with randomly methylated b-cyclodextrin and hydroxypropyl-b-cyclodextrin (HP-fi-CD) was studied by the phase-solubiHty method. The aqueous solubility of CBD and THC increased as a function of CD concentration, and the dissolution increased for THC and CBD cyclodextrin complexes significantly in contrast to plain THC and CBD. These results demonstrate that cyclodextrins increased both the aqueous solubility and dissolution rate... 

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... 

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. 

Direct insertion probe pyrolysis mass spectrometry (DPMS) utilises a device for introducing a single sample of a solid or liquid, usually contained in a quartz or other non-reactive sample holder, into a mass spectrometer ion source. A direct insertion probe consists of a shaft having a sample holder at one end [70] the probe is inserted through a vacuum lock to place the sample holder near to the ion source of the mass spectrometer. The sample is vaporized by heat from the ion source or by heat from a separate heater that surrounds the sample holder. Sample molecules are evaporated into the ion source where they are then ionized as gas-phase molecules. In a recent study, Uyar et al. [74] used such a device for studying the thermal stability of coalesced polymers of polycarbonate, PMMA and polylvinyl acetate) (PVAc) [75] and their binary and ternary blends [74] obtained from their preparation as inclusion compounds in cyclodextrins. 

Elargitai, T., Kaida, Y., and Okamoto, Y., Preparation and chromatographic evaluation of 3,5-dimethylphenyl carbamoylated beta-cyclodextrin stationary phases for normal-phase high-performance liquid-chromatographic separation of enantiomers, J. Chromatogr., 628, 11, 1993. 

Fujimoto, C., Maekawa, A., Murao, Y, Jinno, K., and Takeichi, T., An attempt directed toward enhanced shape selectivity in reversed-phase liquid chromatography preparation of the dodecylaminated beta-cyclodextrin-bonded phase. Anal. Sci., 18, 65, 2002. 

Figure 3.5 Measurement of the chiral purity of commercially available Jacobson s catalyst using a cyclodextrin-based CSP. (a) Lower trace / ,/ -enantiomer product upper trace / ,/ -enantiomer product artificially enriched with S -enantiomer and (b) lower trace S. S -enantiomer product upper trace S. S -enantiomer product artificially enriched with / ,/ -enantiomer. (Conditions CYCLOBOND 1 2000RSP 25 cm X 0.46 cm i.d. mobile phase acetonitrile triethylamine glacial acetic acid [1000 0.5 2.5, v/v] flow rate 1 ml/min temperature ambient detection UV at 240 nm sample preparation 1 mg/ml in acetonitrile injection volume 10 fxl). Reprinted from [19], copyright 1998, with permission of Wiley-Liss, Inc., a subsidiary of John Wiley and Sons, Inc.

Prbpy, 5-(2-MePr)bpy and 5-(2,2-Mc2Pr)bpy have been prepared and characterized. The mer-and /uc-isomers of each complex have been isolated by use of cation-exchange column chromatography as the steric requirements of the R group increase, the percentage of the /uc-isomer decreases. Enantiomers of [Ru(5-Prbpy)3] + were separated on SP Sephadex C-25. Electro-kinetic chromatography has been used to separate the enantiomers of [Ru(104)3] " anionic carboxymethyl-/ -cyclodextrin was employed as the chiral mobile phase additive. ... 

Sinner and Buchmeiser prepared a new class of functionalized monolithic stationary phases (norbornene monoliths) by a ROMP process that tolerates a huge variety of functional monomers [69]. They used this approach in order to chemically attach (3-cyclodextrin onto the monomer prior... 

Three approaches can be employed to separate peptide stereoisomers and amino acid enantiomers separations on chiral columns, separations on achiral stationary phases with mobile phases containing chiral selectors, and precolumn derivatization with chiral agents [111]. Cyclodextrins are most often used for the preparation of chiral columns and as chiral selectors in mobile phases. Macrocyclic antibiotics have also been used as chiral selectors [126]. Very recently, Ilsz et al. [127] reviewed HPLC separation of small peptides and amino acids on macrocyclic antibiotic-based chiral stationary phases. 

Capillary gas chromatography (GC) using modified cyclodextrins as chiral stationary phases is the preferred method for the separation of volatile enantiomers. Fused-silica capillary columns coated with several alkyl or aryl a-cyclo-dextrin, -cyclodextrin and y-cyclodextrin derivatives are suitable to separate most of the volatile chiral compounds. Multidimensional GC (MDGC)-mass spectrometry (MS) allows the separation of essential oil components on an achiral normal phase column and through heart-cutting techniques, the separated components are led to a chiral column for enantiomeric separation. The mass detector ensures the correct identification of the separated components [73]. Preparative chiral GC is suitable for the isolation of enantiomers [5, 73]. 

The preparative-scale separation of enantiomers on chiral stationary phases (CSPs) by GC cannot match the overwhelming success achieved in the realm of liquid chromatography (LC) (Francotte, 1994, 1996 and 2001). Modern commercial instrumentation for preparative-scale GC is not readily available. In contrast to LC, separation factors a in enantioselective GC are usually small (a = 1.01 - 1.20). This is beneficial for fast analytical separations but detrimental to preparative-scale separations. Only in rare instances are large chiral separation factors (a > 1.5) observed in enantioselective GC. Only in one instance, a separation factor as high as a = 10 was detected in enantioselective GC for a chiral fluorinated diether and a modified 7-cyclodextrin (Schurig and Schmidt, 2003) (vide supra). 

Juza, M, Braun, M., and Schurig, V. (1997) Preparative enantiomer separation of the chiral inhalation anesthetics enfiurane, isoflurane and desflurane by gas chromatography on a derivatized 7-cyclodextrin stationary phase, J. Chromatogr. A 769, 119-127. 

Schiirch, S., Saxer, A., Claude, S., Tabacchi, R., Trusch, B., and Hulliger, J. (2001) Semi-preparative gas chromatographic separation of ah-trans-perhydrotriphenylene enantiomers on a chiral cyclodextrin stationary phase, J. Chromatogr. A 905, 175-182. 

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