Enantiomer separation by capillary SFC and GC on immobilized octakis(2,6-di-O-methyl-3-O-pentyl)-γ-cyclodextrin

Heptakis(2,6-di-O-methyl-3-O-pentyl) (2-O-methyl-6-O-oct-1-enyl-3-O-pentyl)-γ-cyclodextrin was immobilized to narrow-bore fused silica capillaries after selective modification. One tert-butyldimethylsilyl group was introduced into octakis-(2-O-methyl-3-O-pentyl)-γ-cyclodextrin in order to get a pure monofunctionalized cyclodextrin derivative. During synthesis the tert-butyldimethylsilyl group was replaced by an anchoring group to bind the cyclodextrin to a polysiloxane. After thermal immobilization of the modified polysiloxane this new chiral stationary phase was applied in GC and SFC. High efficiency separations were obtained in GC. In SFC very polar compounds could be chromatographed at low temperatures resulting in higher separation factors as compared to GC.     

A convenient synthesis of a permethyl-substituted β-cyclodextrin-containing polysiloxane stationary phase using an amide linking group

A novel amide-linked permethyl-substituted β-cyclodextrin-bound polysiloxane stationary phase was prepared in only four steps. First, mono(6-O-toluenesulfonyl)-β-cyclodextrin was treated with sodium azide. Second, the resulting azide derivative was treated with methyl iodide and base followed by reduction with hydrogen to give amine-substituted permethylcyclodextrin 3 . Third, cyclodextrin 3 was treated with p-(allyloxy)benzoyl chloride to form 6^A-(p-allyloxybenzamido)-substituted permethyl-β-cyclodextrin 4 . Lastly, β-cyclodextrin 4 was hydrosilylated onto a polysiloxane backbone containing hydrogen, methyl, and p-tolyl substituents. This new phase separated the enantiomers of certain chiral lactones and alcohols in capillary supercritical fluid chromatography.     

The study of enantioselectivity of all regioisomers of mono‐carboxymethyl‐β‐cyclodextrin used as chiral selectors in CE

This work documents the influence of the position of single carboxymethyl group on the β‐cyclodextrin skeleton on the enantioselectivity. These synthesized monosubstituted carboxymethyl cyclodextrin (CD) derivatives, native β‐cyclodextrin, and commercially available carboxymethyl‐β‐cyclodextrin with degree of substitution approximately 3 were used as additives into the BGE consisting of phosphate buffer at 20 mmol/L concentration, pH 2.5, and several biologically significant low‐molecular‐mass chiral compounds were enantioseparated by CE. The results indicate that different substituent location on β‐cyclodextrin skeleton has a significant influence on the enantioseparation of the investigated enantiomers. The enantioselectivity of 2^I‐O‐regioisomer was better than with native β‐cyclodextrin. Comparable results to native β‐cyclodextrin were obtained for 6^I‐O‐ regioisomer and the enantioselectivity of 3^I‐O‐regioisomer was even worse than with native β‐cyclodextrin. Commercially available derivative of CD provides better resolutions than the monosubstituted carboxymethyl CD derivatives for most of the investigated analytes.     

Influence of substituent position and cavity size of the regioisomers of monocarboxymethyl‐α‐, β‐, and γ‐cyclodextrins on the apparent stability constants of their complexes with both enantiomers of Tröger's base

Enantiomers of Tröger's base were separated by capillary electrophoresis using 2^I‐O‐, 3^I‐O‐, and 6^I‐O‐carboxymethyl‐α‐, β‐, and γ‐cyclodextrin and native α‐, β‐, and γ‐cyclodextrin as chiral additives at 0–12 mmol/L for β‐cyclodextrin and its derivatives and 0–50 mmol/L for α‐ and γ‐cyclodextrins and their derivatives in a background electrolyte composed of sodium phosphate buffer at 20 mmol/L concentration and pH 2.5. Apparent stability constants of all cyclodextrin–Tröger's base complexes were calculated based on capillary electrophoresis data. The obtained results showed that the position of the carboxymethyl group as well as the cavity size of the individual cyclodextrin significantly influences the apparent stability constants of cyclodextrin–Tröger's base complexes.     

2,3-Di-O-pentyl-6-O-tert-butyldimethylsilyl-β-cyclodextrin as a Chiral Stationary Phase in Capillary Gas Chromatography

2,3-Di-O-pentyl-6-O-tert-butyldimethylsilyl-β-cyclodextrin has been evaluated as an enantioselective stationary phase for capillary gas chromatography. Experimental results show a good enantioselectivity towards compounds with different functional groups (haloalkanes, alcohols, esters, terpenoids, amino acid derivatives, and heterocycles). Column stability improves mixing the chiral phase with polysiloxane SE-54 (1 : 1).     

The influence of the substituent position in monocarboxymethyl‐γ‐cyclodextrins on enantioselectivity in capillary electrophoresis

Three newly synthesized chiral selectors, namely, 2^I‐O‐, 3^I‐O‐, and 6^I‐O‐carboxymethyl‐γ‐cyclodextrin, native γ‐cyclodextrin, and commercially available carboxymethylated γ‐cyclodextrin with degree of substitution of 3–6 were used as additives in a background electrolyte composed of phosphate buffer at 20 mmol/L concentration and pH 2.5. This system was used for the analysis of several biologically significant low‐molecular‐mass chiral compounds by capillary electrophoresis. The results confirmed that the position of carboxymethyl group influences the enantioseparation efficiency of all the studied analytes. The 2^I‐O‐ and 3^I‐O‐ regioisomers provide a significantly better resolution than native γ‐cyclodextrin, while the 6^I‐O‐regioisomer gives only a slightly better enantioseparation than native γ‐cyclodextrin. The application of γ‐cyclodextrin possessing higher number of carboxymethyl groups led to the best resolution for the majority of the compounds analyzed.     

Photoirradiation surface molecularly imprinted polymers for the separation of 6‐O‐α‐d‐maltosyl‐β‐cyclodextrin

Photoirradiation surface molecularly imprinted polymers for the separation of 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin were synthesized using functionalized silica as a matrix, 4‐(phenyldiazenyl)phenol as a light‐sensitive monomer, and 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin as a template. Fourier transform infrared spectroscopy results indicated that 4‐(phenyldiazenyl)phenol was grafted onto the surface of functionalized silica. The obtained imprinted polymers exhibited specific recognition toward 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin. Equilibrium binding experiments showed that the photoirradiation surface molecularly imprinted polymers obtained the maximum adsorption amount of 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin at 20.5 mg/g. In binding kinetic experiments, the adsorption reached saturation within 2 h with binding capacity of 72.8%. The experimental results showed that the adsorption capacity and selectivity of imprinted polymers were effective for the separation of 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin, indicating that imprinted polymers could be used to isolate 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin from a conversion mixture containing β‐cyclodextrin and maltose. The results showed that the imprinted polymers prepared by this method were very promising for the selective separation of 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin.     

Per-2,3-O-alkylated β-cyclodextrin duplexes connected with disulfide bonds

Per-2,3-di-O-methyl- and per-2,3-di-O-allyl-β-cyclodextrin duplexes held by two disulfide bonds between their primary faces have been prepared. Permethylation significantly increased the solubility of the cyclodextrin duplexes in a wide range of solvents from water to chlorinated hydrocarbons. Per-2,3-di-O-methylated duplexes are able to form inclusion complexes with organic molecules in aqueous solutions, yet the stability constants are lower by 4–5 orders of magnitude as compared to analogous non-alkylated β-cyclodextrin duplexes.     

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.     

Synthesis and Polymerization of Carbamate-Linked Cyclodextrin Methacrylate Monomers

Abstract

A one-step synthesis for cyclodextrin methacrylate monomers was examined starting from α-, β- and γ-cyclodextrin. The reaction of 2-isocyanatoethyl methacrylate as well as allylisocyanate with the corresponding cyclodextrin gave the monofunctionalized carbamate-linked cyclodextrin methacrylates 2, 6 and 9 and allylcarbamates 11 and 14 in moderate yields. By NMR spectroscopic means, it could be proven that in all cases only the primary 6-hydroxyl groups of the cyclodextrins reacted with the isocyanate group. For the synthesis of a β-cyclodextrin monoallyl compound, a substitution reaction of purchasable 6-O-monotoluenesulfonyl-β-cyclodextrin with allylamine gave 6-N-allylamino-6-deoxy-β-cyclodextrin 18 in high yield. The reaction of 2-isocyanatoethyl methacrylate with α-cyclodextrin to the 6-O-carbamoyl-2-methylpropenoylethyl-α-cyclodextrin (2) was optimized so that the monomer 2 could be prepared on a larger scale without chromatographic separation. The aqueous radical homopolymerization of 2 with the peroxodisulfate/bisulfite redox initiator gave the water soluble cyclodextrin polymer 19 in good yield. Its molecular weight was determined by gel permeation chromatography to be M_n = 101,800 corresponding to an average degree of polymerization P_n = 90.     

Cyclodextrin Derivatives in GC Separation of Racemic Mixtures of Volatiles. Part XIV: Some Applications of Thick-Film Wide-Bore Columns to Enantiomer GC Micropreparation

Representative examples of preparative GC isolation of pure enantiomers in amounts ranging from 0.5 to 2 mg, with thick-film wide-bore open tubular columns coated with cyclodextrin (CD) diluted in polysiloxanes, are described. Two 25 m×0.53 mm i.d. columns, coated with 3 μm of 30% 2,6-di-O-methyl-3-O-pentyl-β-CD/OV-1701 and 2 μm of 30% 2,3-di-O-acetyl-6-O-tert- butyldimethylsilyl-β-CD/PS-086 as stationary phases, were used. Methyl 3-hydroxyhexanoate, methyl 2-methylbutanoate, δ-hexalactone, δ-octalactone, and γ-decalactone (the latter from a nature-identical mango aroma), were submitted to automated micropreparative GC. Average yields of about 30% were achieved when amounts above 20 μg/μl were injected, and an enantiomeric purity above 90% was obtained.     

Unusual peak defocusing in capillary GC on hexakis(2,6-diO-pentyl-3-O-acetyl)-α-cyclodextrin stationary phase

An unusual peak defocusing effect influencing chromatographic performance over a limited range of elution temperatures is described for hexakis(2,6-di-O-pentyl-3-O-acetyl)-α-cyclodextrin stationary phase. Since this phenomenon is likely to be dependent on minor details of the cyclodextrin molecule, full assignment of the ¹H- and ¹³C-NMR-spectra are given.     

水溶性β-环糊精聚合物和疏水改性聚丙烯酰胺的主客体相互作用

主体环糊精聚合物(β-CDE)与客体疏水改性丙烯酰胺共聚物P(AM/POEA)构成超分子结构的高分子识别体系. 这种客体聚合物是含有少量疏水体(x_POEA＜0.01)的水溶性聚合物, NMR测定结果表明β-CDE和P(AM/POEA)的主客体相互作用是通过环糊精空腔和疏水体POEA形成包结络合物进行的. 在P(AM/POEA)聚合物水溶液中加入β-CDE, 由于主客体聚合物相互作用出现粘度的大幅上升, 增粘的幅度可通过改变聚合物浓度和疏水体含量来调节, 同时对盐浓度和温度的影响也进行了研究. 通过透射电镜直观观察的结果表明, 此类缔合聚合物体系的主客体相互作用生成实心球状多分子聚集体.     

The separation of enantiomers on modified cyclodextrin columns: Measurements and molecular modeling

The enantiomers of 2-chloropropionic acid methyl ester, cis-pinane, 2-bromoethylbenzene, 2-bromobutane, 2-hydroxybutane trifluoroacetyl ester, and styrene oxide have been resolved on an octakis-(3-O-butyryl-2,6-di-O-pentyl)-γ-cyclo-dextrin capillary column, and the separation of the styrene oxide enantiomers has also been studied on columns coated with octakis-(3-O-trifluoroacetyl-2,6-di-O-pentyl)-cyclodextrin, octakis-(2,3,6-tri-O-pentyl)-γ-cyclodextrin, heptakis-(3-O-trifluoroacetyl-2,6-di-O-pentyl)-β -cyclodextrin, and heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin. Thermodynamic parameters (ΔG, ΔH, and ΔS) were determined from variable temperature measurements. The inclusion complexes containing styrene oxide were also studied by molecular modeling techniques. It has been found that a combined molecular mechanics–molecular dynamics approach may be a valuable tool for rationalizing the qualitative trends observed in the experimental separation factors. For the inclusion complexes considered here it is shown that the orientation of the guest relative to the cyclodextrin host is determined by the size and polarity of the cyclodextrin.     

Gas chromatographic enantiomer separation of agrochemicals using modified cyclodextrins

The enantiomers of phenoxypropionic acid type herbicides have been resolved by capillary gas chromatography employing modified cyclodextrins as chiral stationary phases. Excellent separations were obtained with columns containing a 1:1 mixture of per-O-pentylated and per-O-methylated γ-cyclodextrin. The enantiomers of the methyl esters of mecoprop and dichlorprop were also resolved on octakis(3-O-butyryl-2,6-di-O-pentyl)-γ-cyclodextrin. On this phase the order of elution of the enantiomers was temperature-dependent, the elution order being reversed as the temperature passed through the isoenantioselective temperature. This is the first time such behavior has been observed with cyclodextrin derivatives. The enantiomers of the polychlorinated polycyclic pesticides cis- and trans-chlordane, oxychlordane, heptachlor, heptachlorepoxide, and three chiral organophosphorus pesticides could be resolved using selectively derivatized cyclodextrin derivatives.     

Comparison of Different Di‐tert‐butyldimethyl‐Silylated Cyclodextrins as Chiral Stationary Phases in Capillary Gas Chromatography

Separation factors and thermodynamic data for the separation of various chiral analytes on different di‐O‐tert‐butyldimethyl‐silylated cyclodextrin derivatives are collected and described. Modifying the substitution pattern of the tert‐butyldimethylsilyl group in position 2 and 3 or changing from β‐ to γ‐cyclodextrin significantly affects the separation properties of the cyclodextrin derivatives.     

Gas chromatographic separation of the stereoisomers of organophosphorus chemical warfare agents using cyclodextrin capillary columns

The synthesis of the organophosphorus nerve agents sarin, tabun, and cyclohexyl methylphosphonofluoridate (GF) produces a mixture of two stereoisomers except for soman where four stereoisomers are produced. Significant differences exist in the reported toxicity and AChE inhibition rates of the various stereoisomers. This makes the ability to distinguish between the different stereoisomers desirable. Five different derivatized cyclodextrin stationary phases developed for gas chromatography were tested for their ability to resolve the nerve agent stereoisomers using a gas chromatograph interfaced to an atomic emission detector. Of the five columns that we examined, only the 2,6-di-O-pentyl-3-O-trifluoroacetyl or 2,6-di-O-pentyl-3-O-butyryl γ-cyclodextrins were able to successfully resolve all four soman stereoisomers. The elution order for each column was determined using solutions of isolated soman stereoisomers. Enantiomers of sarin, tabun, and GF were resolved with varying degrees of success on the different cyclodextrin stationary phases. Only the butyryl γ-cyclodextrin was able to separate the enantiomers of all four of the nerve agents examined in this study. The capacity (k) and selectivity (α) factors were determined for each of the chemical warfare agents successfully separated. The TNO Prins Maurits Laboratory in the Netherlands has previously developed several different chromatographic methods to resolve the stereoisomers of soman, sarin, and tabun. The advantage of the method described here is that commercially available cyclodextrin gas chromatography columns were used to resolve the stereoisomers, thereby facilitating rapid and routine analysis of organophosphorus nerve agents.     

One Convenient Preparation and Characterization of a New Amphiphilic Cationic Cyclodextrin Derivative 2-O-(Hydroxypropyl-N,N-Dimethyl-N-Dodecylammonio)-β-Cyclodextrin

A new amphiphilic cyclodextrin derivative 2-O-(hydroxypropyl-N,N-dimethyl-N-dodecylammonio)-β-cyclodextrin (2-HPDMDA-β-CD) was prepared and characterized by surface tension, electrical conductivity, dynamic light scattering, transmission electron microscopy (TEM) and steady-state fluorescence. 2-HPDMDA-β-CD was found to be a fine surfactant with a smaller critical micelle concentration (1.21 mM) value than that of dodecyltrimethylammonium chloride. TEM showed that 2-HPDMDA-β-CD could form two kinds of spherical aggregates in solution. The smaller one showed little concentration dependence while the larger one showed relatively strong concentration dependence. 2-HPDMDA-β-CD could be a fine host compound in molecular recognition with two functional spaces of the cyclodextrin cavity and micelles.     

Synthesis and Silica‐Based Immobilization of Monofunctionalized Heptakis(2,6‐di‐O‐methyl‐3‐O‐pentyl)‐β‐cyclodextrin for Enantioselective Capillary‐HPLC

Heptakis(2,6‐di‐O‐methyl‐3‐O‐pentyl)‐β‐cyclodextrin was monofunctionalized by the regioselective introduction of exactly one ω‐epoxyoctyl group at the primary site of the cyclodextrin. The site‐specifically substituted cyclodextrin was immobilized to commercially available aminopropyl silica by nucleophilic opening of the epoxy function of the spacer substituent resulting in a lipophilic chiral stationary phase with broad applicability for enantiomer separations in capillary‐HPLC under reversed‐phase conditions.     

Permethylated cyclodextrins in the GC separation of racemic mixtures of volatiles: Part 1

The chromatographic separation of racemic mixtures of volatile compounds by 2,3,6-trimethyl-α-, β- and γ-cyclodextrins is discussed. Columns were prepared by mixing the derivatized cyclodextrin with OV-1701 or hydroxy-terminated OV-1701 (OV-1701-OH) following Schurig's method [1]. About 130 racemates with widely differing structures were used to test the performances of 2,3,6-permethylated-α, β- and, γ-cyclodextrins mixed with the polysiloxane polymers in different ratios. The influence of the different types of cyclodextrin on racemate separation is shown, and some phenomena which might be helpful in the elucidation of the chromatographic behavior involved are also described. The influence both of the percentage of cyclodextrin in the polysiloxane, and of the operating conditions (carrier gas, flow rate, and temperature) in the separation of flavor and fragrance racemates is also evaluated.