Cyclodextrin derivatives in the GC separation of racemic mixtures of volatile compounds: Part IV

This paper reports the chromatographic performance of columns coated with 2,3,6-trimethyl-α-, β-, and γ-cyclodextrins (2,3,6-TriMe-α,- β-, and γ-CD) and their derivatives 2,6-dimethyl-3-trifluoroacetyl-α-, β-, and γ-cyclodextrins (2,6-DiMe-3-TFA-α-, β-, and γ-CD), all six diluted in polysiloxane, for the separation of the enantiomers of volatile compounds. The influence of column length and film thickness on separation is reported. Phenomena related to reproducibility and consistency, over a period of time, of columns prepared with these CD derivatives are also discussed, and a possible solution to some drawbacks reported here is proposed.     

Cyclodextrin derivatives in the GC separation of racemic mixtures of volatile compounds,part V: Heptakis 2,6-dimethyl-3-pentyl-β-cyclodextrins

This paper describes an evaluation of the chromatographic performance of columns coated with amorphous cyclodextrin (CD) derivatives, in particular 2,3,6-tripentyl-β-CD (2,3,6-TriPe-β-CD), 2,6-dipentyl-3-methyl-β-CD (2,6-DiPe-3-Me-β-CD), and 2,6-dimethyl-3-pentyl-β-CD (2,6-DiMe-3-Pe-β-CD), all diluted in polysiloxane (OV-1701 or OV-1701-OH), for the separation of the enantiomers of volatile compounds. 2,6-DiMe-3-Pe-β-CD in OV-1701 offers performance comparable with (or better than) that of the other two CDs, and without their drawbacks (inconsistency of results, as described previously). This article compares the separating ability of 2,6-DiMe-3-Pe-β-CD and 2,3,6-TriMe-β-CD, and describes the influence of the CD derivative to polysiloxane ratio, the minimum operating temperatures of the columns, and the reproducibility and consistency of performance of columns coated with the former CD derivative diluted in polysiloxane.     

Cyclodextrin derivatives for the GC separation of racemic mixtures of volatile compounds. Part VI: The influence of the diluting phase on the enantioselectivity of 2,6-Di-O-methyl-3-O-pentyl-β-cyclodextrin

As a continuation of previous studies on the use of cyclodextrin derivatives (CD) for the separation of volatile compounds by capillary GC, the influence of diluting phases other than OV-1701 or OV-1701-OH has been investigated. 2,6-Di-O-methyl-3-O-pentyl-β-cyclodextrin (2,6-DiMe-3-Pe-β-CD) was taken as the reference CD derivative, because of the large number of volatile racemates it is able to separate; OV-1701 or OV-1701-OH was chosen as the reference diluting phase. The performance of a column coated with a 0.15 μm film of 10 % 2,6-DiMe-3-Pe-β-CD in OV-1701 was compared with that of analogous columns coated with films of the same thickness containing the same percentage of the CD derivative diluted with stationary phases of different polarity, i.e. PS-086, PS-347.5, and OV-225. Resolution values and separation factors of thirty racemates were used to evaluate the effect of different diluting phases on column performance.     

Cyclocholates as Chiral Selectors for Capillary Gas Chromatography – Effect of Temperature Conditioning on the Chromatographic Behavior of the Stationary Phase

The suitability of cyclocholates as chiral selectors in gas chromatography has been evaluated. We present the synthesis and characterization of two cyclocholates, viz. 3α,7α-diacetoxycyclo[3]cholate and 3α,7α-diacetoxycylo[4]cholate. Mixtures of these new selectors with polysiloxanes were tested as chiral stationary phases in capillary gas chromatography. Several enantiomer separations of common racemates were achieved with the 3α,7α-diacetoxycyclo[3]cholate at 10% in OV-1701 (w/w). It was shown that column efficiency was strongly dependent on temperature and that enantioselectivity was very sensitive to column conditioning. This chromatographic behavior suggested that cyclocholates were only dispersed in polysiloxane. Thus, it was assumed that chiral discrimination occurred via enantioselective adsorption interactions of enantiomers at the surface of the solid chiral selector dispersed in the polysiloxane matrix OV-1701.     

Retention on mixed cyclodextrin/polysiloxane stationary phases in capillary GC—Evidence for the interaction of cyclodextrin and polysiloxane

The dependence of the retention on stationary phases consisting of mixtures of a cyclodextrin (perpentyl-β-cyclodextrin) and a polysiloxane (cyanopropyl-7%-, phenyl-7%-methyl-86%-or OV-1701) was investigated as function of the cyclodextrin concentration. In order to study the effect of mixing, the data on the mixed stationary phases were compared with those obtained on pure OV-1701 and perpentylated β-CD and on coupled columns, individually coated with the pure phases. The validity of the retention model proposed in the literature by Schurig and co-workers was checked. Deviation from linearity was observed for some racemates. A possible explanation of the deviation is presented and a more general retention model on mixed cyclodextrin-polysiloxane phases is proposed.     

Thermal Decomposition of Toxaphene Congeners by High Resolution Gas Chromatographic Phases

Some toxaphene congeners are thermally unstable under commonly used gas chromatographic temperature conditions. The thermal stability of the 22 commercially available congeners has been studied at four different heating rates on four stationary phases Ultra 2 (5%-diphenyl-95%-dimethylpolysiloxane), a liquid crystalline phase (N,N′-bis(p-butoxy-benzylidene)-α,α′-bis-p-toluidine), Rtx-2330 (90%-biscyanopropyl-10%-phenylcyanopropyl-polysiloxane), and heptakis-(2,3,6-O-t-butyldimethylsilyl)-β-cyclodextrin (TBDMS-CD) diluted in OV-1701-OH. A substantial degradation of the congeners Parlar 39, 42, 50, 56, 58, and 62 could be observed on the cyanopropyl polysiloxane stationary phase. Furthermore, the applied temperature program and stationary phase had an influence on the signal areas. These factors are important for a quantitative analysis.     

A chiral porous organic cage for molecular recognition using gas chromatography

Molecular organic cages as shape-persistent organic molecules with permanent and accessible cavities have attracted a lot of interest because of their importance as host-guest systems. Herein, we report a chiral porous organic cage (POC) CC9 diluted with a polysiloxane OV-1701 to fabricate a CC9-coated capillary column, which was used for the high-resolution gas chromatographic separation of organic compounds, including positional isomers and racemates. On the CC9-coated capillary column, a large number of racemic compounds such as chiral alcohols, esters, ethers and epoxides can be resolved without derivatization. By comparing the chiral recognition ability of the CC9-coated column with the commercially available β-DEX 120 column and the POC CC3-R coated column recently reported by our group, the CC9-coated column offered good resolution during the separation of some racemates, that were not separated using the β-DEX 120 column or POC CC3-R coated column. Therefore, the CC9-coated column can be complementary to the β-DEX 120 column and CC3-R coated column. The results indicated that the CC9-coated column exhibited great potential for application in the separation of positional isomers and enantiomers with great selectivity, high resolution and good reproducibility.     

Electrophoretic separation strategy for chiral pharmaceuticals using highly-sulfated and neutral cyclodextrins based dual selector systems

The enantiomeric separation of chiral pharmaceuticals was investigated using dual systems with mixtures of cyclodextrin derivatives. The dual cyclodextrin systems, consisting of one highly-sulfated (α-, β-, and γ-HSCD) and one neutral cyclodextrin, i.e. either heptakis (2,3,6-tri-O-methyl)-β-CD (TMCD), heptakis (2,6-di-O-methyl)-β-CD (DMCD) or hydroxypropyl-β-CD (HPCD), are tested on 25 pharmaceutical compounds with different acid-basic properties (16 basics, 8 acids and 1 neutral). The influence on the separation of the type and concentration of neutral CD in highly-sulfated cyclodextrins-based dual selector systems, is investigated. For 11 of 16 basic compounds, a better separation is obtained with the CD mixtures compared to the use of only a highly-sulfated CD. Mixtures with TMCD give better results than those with DMCD and HPCD. Results showed that dual CD systems are useful to achieve and to optimise chiral separations of compounds not (sufficiently) separated with HSCDs alone. For example, ibuprofen was not resolved with α-, β- or γ-HSCD, but could be separated with the mixture 25 mM TMCD and 5% HS-β-CD. Based on the obtained results, a dual CD systems based separation strategy is defined.     

Extending the scope of enantiomer separation on diluted methylated β-cyclodextrin derivatives by high-resolution gas chromatography

High-resolution open-tubular columns coated with solutions of heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (Phase I) or heptakis(2,6-di-O-methyl-3-O-trifluoroacetyl)-β-cyclodextrin (Phase II) in moderately polar polysiloxanes such as OV-1701 (5% cyanopropyl/7% phenyl/88% methylpolysiloxane) and OV-225 (25% cyanopropyl/50% phenyl/25% methylpolysiloxane) are used for the gas chromatographic enantiomer separation of volatiles belonging to different classes of compounds. No derivatization procedures are necessary for most of the resolved chiral molecules. The chiral stationary phases can be operated between 25 and 190°C for extended periods of time. The enantiomer separation of saturated, unfunctionalized hydrocarbons clearly demonstrates the importance of molecular inclusion in chiral recognition using cyclodextrins for this class of compounds. The different, and in some cases complementary, selectivity of the Phases I and II is demonstrated.     

Gas chromatographic separation of the enantiomers of flumecinol and some related compounds

Flumecinol and related compounds can, without derivatization, be separated into their enantiomers by gas chromatography on cyclodextrin phases; permethylated β-cyclodextrin dissolved in OV-1701 can be particularly recommended. Thermodynamic data describing the different intensities of interaction of the individual enantiomers with the stationary phases were determined. The values measured imply different separation mechanisms for the compounds investigated.     

Enantioselective HRGC Separation of Toxaphene Congeners by Ethylated γ‐Cyclodextrins

The enantioselectivity of three batches of octakis‐(2,3,6‐tri‐O‐ethyl)‐γ‐cyclodextrin (TEG‐CD), which differed significantly in their degree of ethylation, is reported for toxaphene congeners. The cyclodextrin composition was determined by high performance liquid chromatography‐mass spectrometry. Columns prepared with almost fully ethylated cyclodextrin showed no enantiomer separation. Increasing the average number of free OH groups up to an optimum of 3.8 allowed to resolve the following toxaphene congeners into enantiomers: Parlar no. 11, 12, 15, 21, 25, 32, 38, 42.1, 42.2, 50, 51, 56, 58, 59, 62, 69 as well as B8‐1412. More free OH groups did not improve the enantiomer resolution. The structure of the polysiloxane used for dilution of TEG‐CD also had an influence on the enantiomer separations achieved. Compared to OV 1701‐OH, the use of PS 086 significantly improved the enantiomer resolutions of the separated congeners. However, neither increasing the column length nor the cyclodextrin amount in the stationary phase led to better separation results.     

Capillary gas chromatographic separation of C10–C12 secondary phenylalkanes on modified cyclodextrin stationary phases

The separation of isomers and enantiomers of branched C₁₀-C₁₂ phenylalkanes by gas chromatography on fused silica capillary columns coated with some modified β- and γ-cyclodextrins was studied. It was shown that the separation of positional isomers of C₁₀-C₁₂ phynylalkanes on modified cyclodextrin capillary columns is not better than that on a column coated with modified polyethylene glycol. Differences were found in the enantioselectivity of modified β- and γ-cyclodextrins for the separation of C₁₀-C₁₂ secondary phenylalkane enantiomers. While alkylderivatives of β-CDs resolve enantiomers of 3-phenylalkanes, alkyl derivatives of γ-CD resolve enantiomers of 2-phenylalkanes. Since shape selectivity factors of modified cyclodextrins have indicated no inclusion of the considered solutes in cyclodextrin cavities, enantioselective interactions most probably occur on the outer sphere of cyclodextrins.     

Separation of neutral and basic enantiomers by cyclodextrin electrokinetic chromatography using anionic cyclodextrin derivatives as chiral pseudo-stationary phases

Separations of neutral and basic racemates were performed using five different anionic cyclodextrin (CD) derivatives as chiral selectors, viz. carboxymethylated β-CD, β-CD phosphate sodium salt, sulfobutyl ether β-CD sodium salt, carboxymethylated γ-CD, and γ-CD phosphate sodium salt. For the separation of neutral racemates, an untreated fused silica capillary was employed and various neutral racemates were successfully separated. Since the pH of the buffer affected the electroosmotic flow (EOF), the resolution was improved by changing the buffer pH. A polyacrylamide coated capillary was employed for the separation of basic racemates to suppress EOF and to prevent adsorption of cationic analyte on the capillary surface. By choosing an appropriate type and concentration of anionic CD, about 40 basic racemates were successfully separated. Some rough binding constants of basic analytes with an anionic β-CD were measured to discuss the optimum concentration of the CD. The migration direction was dependent on the binding constants and the concentration of the CD. The analyte strongly bound to the anionic CD migrated towards the anode but the weakly bound one moved towards the cathode. Anionic γ-CDs were also very useful for the separation of basic enantiomers. Five neutral CDs were employed as chiral selectors to compare selectivity between charged and neutral CDs, and eleven racemates could only be resolved using anionic CDs. The separation of some basic racemates in human plasma was also described. The direct injection of plasma samples was possible for some enantiomers that did not interact strongly with plasma proteins.     

6-tert-Butyldimethylsilyl-2,3-dimethyl-α-, β-, and γ-cyclodextrins,dissolved in polysiloxanes,as chiral selectors for gas chromatography. Influence of selector concentration and polysiloxane matrix polarity on enantioselectivity

The enantioselectivity of three chiral selectors, 6-t-butyldimethyl-silyl-2,3-dimethyl-α-, β- and γ-cyclodextrin (TB-α-CD, TB-β-CD, TB-γ-CD), are compared and discussed for a range of chiral test compounds. TB-β-CD in particular offers high enantioselectivity for a variety of chiral compounds and has the special property of excellent solubility in different alkylpolysiloxanes, including the weakly polar variety, because of its weak self-association. To investigate the influence of the polarity of polysiloxane matrices this selector can be used at a wide range of concentrations in the most suitable polysiloxane matrices and at low separation temperatures without impairment of resolution by peak broadening and symmetry distortion.     

Extending the scope of enantiomer separations on Chirasil-Dex by GLC: Comparison with permethylated β-cyclodextrin dissolved in OV-1701

GLC on polysiloxane-anchored permethylated β-cyclodextrin (Chirasil-Dex) has been used to separate the enantiomers of 106 racemates of different classes of compounds ranging from alkanes to highly polar compounds such as underivatized diols and free acids. Chromatographic data are listed and compared with those obtained by GLC on permethylated β-cyclodextrin dissolved in OV-1701.     

Carboxymethylated cyclodextrin derivatives as chiral NMR discriminating agents

Procedures to prepare cyclodextrins with carboxymethyl groups incorporated selectively at the primary (6-position) or secondary (2-position) are described. Complexation properties of the primary and secondary carboxymethylated derivatives of α-, β-, and γ-cyclodextrins are compared to native cyclodextrins and indiscriminately substituted carboxymethylated cyclodextrins, using pheniramine, chlorpheniramine, and brompheniramine as substrates. The stoichiometry of association of these substrates with the α-cyclodextrins is 1:1, whereas with the γ-cyclodextrins, a 2:1 substrate:cyclodextrin complex forms. Data for the β-cyclodextrins suggest that there is a mix of 1:1 and 2:1 substrate–cyclodextrin complexes. The position of the carboxymethyl groups on the cyclodextrin does not appear to alter the geometry of substrate–cyclodextrin association. The effectiveness of the carboxymethylated cyclodextrins as chiral NMR discriminating agents is compared with the native cyclodextrins. In all cases, the indiscriminately substituted α-, β-, and γ-cyclodextrins are more effective at enantiodistinction with the cationic substrates than native cyclodextrins or the derivatives with carboxymethyl groups at the primary or secondary positions. Among α-, β-, and γ-indiscriminately substituted cyclodextrins, there was no clearly optimal candidate for chiral NMR discrimination studies. The indiscriminately substituted carboxymethyl cyclodextrins are effective water-soluble chiral NMR discrimination reagents for cationic substrates.     

A β-cyclodextrin covalent organic framework used as a chiral stationary phase for chiral separation in gas chromatography

Chiral covalent organic frameworks(CCOFs) featuring chirality, stability, and good porosity have attracted a considerable amount of attention due to their important applications, such as asymmetric catalysis, chiral separation, and chiral recognition. In this study, a β-cyclodextrin(β-CD) covalent organic framework(β-CD-COF) diluted with polysiloxane OV-1701 was explored as a novel chiral stationary phase(CSP) for gas chromatography(GC) separation of racemates. The β-CD-COF coated capillary colu...     

Enantiomer separation by gas chromatography on cyclodextrin chiral stationary phases

Fused silica capillary columns coated with several alkyl or acyl cyclodextrin derivatives, especially those of α- and β-cyclodextrins, are suitable for the enantiomer separation of a wide variety of volatile compounds of different molecular size and functionality. Positional isomers and more than 250 pairs of optical isomers have been resolved, including chiral hydrocarbons, acetals, ethers, epoxides, carbonates, lactones, esters, acids, ketones, aldehydes, alcohols, halocarbons, and also nitrogen-and sulfur-containing compounds. The physical properties of the cyclodextrin derivatives, even those obtained as viscous fluids, could be improved by dissolving them in polysiloxane liquid phases commonly used for GLC.     

Separation of Cyclodextrins Using Cyclodextrin Bonded Phases

Abstract

Two different cyclodextrin bonded phases (α and β) were used for the separation of α-, β-and γ-cyclodextrins. The β-cyclodextrin phase was found to be, in general, more effective at resolving the cyclodextrins than the α-cyclodextrin bonded phase. Acetonitrile/water mixtures were used as mobile phases. The effect of mobile phase composition on retention and resolution is examined. The elution order was found to be size dependent. The results are discussed in terms of the overall retention mechanism.