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.     

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.     

Enantiomeric discrimination of aromatic-containing anionic substrates using cationic cyclodextrins

Cationic α-, β-, and γ-cyclodextrins were prepared by reacting the corresponding native cyclodextrin (CD) with glycidyltrimethylammonium chloride (GTAC). The reaction conditions were varied in order to alter the degree of substitution of GTAC units on the cyclodextrin. The CD-GTAC derivatives, which retain a positive charge independent of pH, were evaluated as water-soluble chiral NMR solvating agents for anionic substrates. The CD-GTAC derivatives are considerably more effective at causing enantiomeric discrimination in the ¹H NMR spectra of aromatic-containing anionic substrates than the neutral native cyclodextrins. Derivatives with a degree of substitution of about 1.5 were more effective than those with lower or higher degree of substitution. Not one of the α-, β-, and γ-CD-GTAC derivatives was consistently the most effective at causing enantiomeric discrimination for all of the substrates examined herein.     

Sorption of phenols by single and mixed cyclodextrin polymers

Cyclodextrin (CD) hydrogels were synthesized by a crosslinking reaction with the same cyclodextrin/epichlorohydrin mole ratio (1/11) using αCD, βCD, γCD, and 50:50 mixtures of α/βCD and β/γCD. In order to investigate the sorption capacity of these hydrogels to different solutes, five model molecules have been selected: phenol, 3-nitrophenol, 4-nitrophenol, 1-naphthol, and the antiinflamatory drug diflunisal. The amounts sorbed have been related to the different affinities of the solutes. 1-naphthol shows the highest affinity for these polymers, especially in the case of sorbents containing βCD. The sorption is considerably poorer for phenol than for its nitro derivatives. The two structural isomers 3- and 4-nitrophenol show significant differences in their affinities towards αCD, βCD and α/βCD. Finally, in the case of diflunisal, a bulkier model molecule, remarkable differences were found on the sorption behaviour by polymers whose cyclodextrins have a similar affinity for this solute (βCD, γCD, and β/γCD).     

A comparative study of complexation of enalapril with α-, β- and γ-cyclodextrins in aqueous medium: structure elucidation of inclusion complexes using NMR spectroscopic and molecular mechanics methods

Structural studies of complexes of enalapril maleate with α-, β- and γ-cyclodextrins were carried by NMR spectroscopy and computational methods. The formation of complexes of enalapril with all the three cyclodextrins was established by chemical shift changes observed in the cavity protons of cyclodextrins in the presence of enalapril maleate. The stoichiometry of the complexes was determined to be 1:1 by ¹H NMR titrations studies using Scott’s method. Intermolecular cross peaks observed in the 2D ROESY spectra of mixtures of enalapril maleate with three cyclodextrins helped in establishing the probable structures of these inclusion complexes which were supported by molecular mechanics (MM2) studies. Enalapril forms 1:1 inclusion complex with all the studied cyclodextrins through aromatic ring. The mode of approach of aromatic ring to the α-cyclodextrin cavity was found to be different from those of β- and γ-cyclodextrins, which were identical.     

Exploring the rotational isomerism in non-classical Wells-Dawson anions {W18X}: a combined theoretical and mass spectrometry study

We present a combined theoretical and mass spectrometry study of the rotational isomerism of the non-classical Wells-Dawson anions. The structure is larger than the Keggin anion and six geometric isomers are predicted (α, β, γ, α*, β*, γ*) on the basis of structural arguments. This work explores the geometrical differences between the isomers and evaluates the stability of these unusual clusters based upon the inclusion of the different heteroatoms. We connect the theoretical results with experimental studies by exploring the fragmentation of the parent clusters by electrospray-ionisation mass spectrometry (ESI-MS). Both approaches show a general stability trend that can be postulated as follows: γ* > β* > α* > α ? β > γ where the isomers γ*, β* and α are the only anions of this type known to have been synthesised.     

环糊精对手性药物伪麻黄碱分子识别的电喷雾飞行时间质谱研究

用电喷雾正交飞行时间质谱仪分别研究了以α－环糊精、β－环糊精和γ－环 糊精作为手性拆分剂对手性药物伪麻黄碱的分子识别效应,同时还分别研究了 Nozzle电的变化对α－环糊精和γ－环糊精的手性识别的影响。在质谱图中能明显 反映出三种手性拆分剂都具备很强的手性识别能力,随Nozzle电压的改变,三种手 性拆分剂双分别具有各自的手性识别特征。     

Preparation of Cyclodextrin Nitrates

Nitration of α-, β-, and γ-cyclodextrins with nitric acid of various concentrations was studied. The nitration occurs similarly for all the three cyclodextrins studied. The influence of the reaction conditions on the degree of substitution of hydroxy groups in cyclodextrin by nitrate groups was examined. The composition and degree of substitution of the nitration products depend not only on the nitric acid concentration, but also on the molar ratio of HNO₃ to OH groups. The results obtained allow optimization of the procedure for preparing cyclodextrin nitrates with definite topology of substitution of cyclodextrin hydroxy groups.

     

Selective Interactions of Cyclodextrins with Isomeric 1,2,4-Thiadiazole Derivatives Displaying Pharmacological Activity: Spectroscopy Study

Complex formation of α-, β- and γ-cyclodextrins with 1,2,4-thiadiazole derivatives, which are structural isomers displaying an activity in the treatment of Alzheimer’s disease, was examined by the use of ¹H NMR and UV-spectroscopy. Stability constants of the complexes formed between cyclodextrins and thiadiazoles in two different buffers (pH 1.2 and 7.4) were calculated and analyzed. The temperature dependences of the stability constants were used to evaluate the enthalpy and entropy changes of complex formation. It was demonstrated that selectivity of the interactions between cyclodextrins and isometric 1,2,4-thiadiazole derivatives is determined by the size of macrocyclic cavity and relative position of the side groups in the benzene ring of the guest molecules. Higher stability of the complexes in the acidic medium (pH 1.2) in comparison with the slightly alkaline solution (pH 7.4) is caused by the important role of surface interactions.     

Preparation and Properties of Inclusion Compounds of Cyclodextrins with Organotransition Metal Complexes

Inclusion compounds of transition metal complexes of cycloocta-1,5-diene (cod) and norbornadiene (nbd) with cyclodextrins were prepared. Two-to-one (cyclodextrin:guest) inclusion compounds were obtained in high yields by the treatment of β-cyclodextrin (β-CD) with [(L)RhCl]₂ (L = nbd or cod) and 1:1 inclusion compounds were obtained by the reaction of β-CD with (cod)PtX₂ (X = Cl, Br, or I) in high yields, while γ-CD formed 1:1 inclusion compounds with (cod)PtX₂ (X = Br or I). The formation of inclusion compounds is selective. α-CD did not form inclusion compounds with any transition-metal complexes with cycloocta-1,5-diene. Thermogravimetric measurements show that the complexes are stabilized by inclusion in cyclodextrin cavities. The inclusion compounds were characterized by ¹ H-NMR, IR, UV, and circular dichroism spectra.     

Formation of nanotubes and secondary assemblies of cyclodextrins induced by BBOT

The study of cyclodextrin nanotubes is a significant topic among the self-assembly behaviors of cyclodextrins. We report herein the interaction of 2,5-bis(5′-tert-butyl-2-benzoxazoyl)thiophene (BBOT) with α-, β-, γ-cyclodextrins (CDs). It has been discovered that the reaction patterns of BBOT with CDs are remarkably different. β-CD forms a simple inclusion complex with BBOT in a stoichiometry of 1:2 (guest:host). β-CD forms a 1:1 inclusion complex with BBOT at its low concentration. At higher concentration of BBOT, the nanotube and secondary assembly of β-CD are formed. As for γ-CD, the nanotube and secondary assembly are formed within the whole concentration range of BBOT studied. The structure of γ-CD nanotubes is different from that of β-CD nanotubes to a certain extent.

     

含氮基团修饰β-环糊精量子化学研究

用PM3半经验方法优化了5种不同含氮基团修饰环糊精的结构,并用HF方法在STO-3G和3-21G*两种基组水平上计算了它们的单点能.首次给出了这5种修饰环糊精的优化结构,同时计算结果采用极性基团会增加修饰环糊精的偶极距,优化的结构及计算出的物理性质表明修饰后产物明显与β-环糊精有明显的差别.     

Cyclodextrin Inclusion Compounds in Research and Industry

α-, β-, and γ-Cyclodextrins are cyclic oligosaccharides consisting of six, seven, or eight glucose units, which can be obtained on a large scale from starch. They form inclusion compounds with smaller molecules which fit into their 5—8 Å cavity. These (crystalline) complexes are of interest for scientific research as, contrary to the classical clathrates, they exist in aqueous solution and can be used to study the hydrophobic interactions which are so important in biological systems. Cyclodextrins also serve as models both for polymeric starch and, in the form of their polyiodide complexes, for “blue iodine-starch”. As cyclodextrins catalyze several chemical reactions they and their functionalized derivatives provide useful enzyme models. Cyclodextrins can be used to advantage in the production of pharmaceuticals, pesticides, foodstuffs, and toilet articles—the (micro-encapsulated) active and aromatic substances enclosed within them are protected from the effects of light and atmosphere and can be easily handled and stored in powder from. Substances which are not very soluble in water become more soluble in the presence of cyclodextrins—creams and emulsions can be stabilized, and the growth and yield of grain harvests can be increased. Cyclodextrins can be chemically modified for many different purposes; polymerized cyclodextrin or cyclodextrin bound to a polymer carrier have already been employed in gel inclusion and affinity chromatography.     

Diffusion Measurements vs. Chemical Shift Titration for Determination of Association Constants on the Example of Camphor–Cyclodextrin Complexes

Measurements on camphor–cyclodextrin complexes reveal that precise association constants are more easily determined by chemical shift titration. Diffusion measurements using HR-DOSY allow easy following of the complex composition at different concentration ratios and estimation of the binding energy. Linear dependence of the diffusion coefficients on the molecular mass of free and associated cyclodextrins has been observed in D₂O. The solution structures of α- and β-cyclodextrin complexes of camphor in D₂O were deduced from intermolecular cross-relaxation data. Different preferential orientation in the 2:1 α-CD and 1:1 β-CD species have been derived in contrast to the loose 1:1 complex with γ-CD. Proton NMR chemical shift values proved to be much more sensitive to diastereomeric complex formation than diffusion coefficients.     

Inhibition of cyclodextrins on the activity of α-amylase

α-amylase activity influences both flour fermentation process and the quality of the fermented products due to its ability of breaking starch into smaller units. The inhibition of cyclodextrins on α-amylase activity was investigated in this paper. Experiment results showed that hydrophobic cavity size was an intrinsic factor during the inhibition processing. Among three types of cyclodextrin (α-, β- and γ-), β-type exhibited the most significant inhibitory activity toward α-amylase. The optimal inhibitory parameters were indicated to be pH 5.9, concentration of β-cyclodextrins 1 mmol/L, reaction temperature 45 °C and reaction time 60 min. Results suggested that the endogenous fluorescence of α-amylase was inhibited by cyclodextrins. Circular dichroism spectrum indicated that the secondary structure of α-amylase, including α-helices, β-sheets and random coils, was changed by cyclodextrins. All the results in this paper aim to provide a further understanding for α-amylase in the industry application.     

Preparation and properties of cyclodextrin-metal carbonyl inclusion compounds

One-to-one inclusion compounds were obtained in a crystalline state in high yields by treatment if ironpentacarbonyl and dimanganesedecacarbonyl with γ-cyclodextrin. These represent the first examples of cyclodextrin inclusion compounds with binary metal carbonyl complexes; the metal carbonyl complexes included in cyclodextrins are thermally more stable than the free complexes.     

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.     

Novel pyrrolo-quinazolino-quinoline analogues of the natural alkaloids and their inclusion molecular complexes in the native cyclodextrins: experimental versus theoretical study

A series ten novel analogs based on a novel template pyrrolo-quinazolino-quinolines, containing Luotonin-A (Luot-A) and 14-aza-camptothecin (14-aza-CPT) molecular core as well as their inclusion complexes in the native α- (α-CD), β- (β-CD) and γ- (β-CD) cyclodextrins were obtained. The physical properties of the alkaloids and corresponding molecular complexes with cyclodextrins are elucidated experimentally by the electronic absorption and CD-spectroscopy, electrospray ionization and matrix-assisted laser desorption/ionization mass spectrometry and nuclear magnetic resonance method. The experimental data are supported by the theoretical quantum chemical calculations of the molecular and electronic structures as well as physical properties in condense phase.     

Bile pigment complexes with cyclodextrins: electronic and vibrational circular dichroism study

Chiral recognition of bilirubin IX-α, biliverdin IX-α, and bilirubin ditaurate dianions by cyclodextrins was studied using a combination of vibrational and electronic circular dichroism. Biliverdin forms inclusion complexes with β-cyclodextrin and β-methylcyclodextrin. Bilirubin bonds to both cyclodextrins by means of hydrogen bonds and only shallow inclusions that are restricted by the presence of COO⁻ in the pigment structure. Bilirubin ditaurate complexes are realized by a weak inclusion of the whole molecule, or some part of it, into the cyclodextrin cavity and stabilization of the conformation by hydrogen bonds. Bilirubin and bilirubin ditaurate can be recognized by cyclodextrin and methylcyclodextrin in the form of opposite conformers. Spectroscopic characteristics of the different conformations of the bile pigments were obtained for the first time by vibrational circular dichroism techniques.     

Separation of terbutaline enantiomers in capillary electrophoresis with neutral cyclodextrin-type chiral selectors and investigation of the structure of selector-selectand complexes using nuclear magnetic resonance spectroscopy

The major goal of this study was to determine the affinity pattern of the terbutaline (TB) enantiomers toward α-, β-, γ-, and heptakis(2,3-di-O-acetyl)-β-cyclodextrins and using NMR spectroscopy for the understanding of the fine mechanisms of interaction between the cyclodextrins (CD) and TB enantiomers. It was shown once again that CE in combination with NMR spectroscopy represents a sensitive tool to study the affinity patterns and structure of CD complexes with chiral guests. Opposite affinity patterns of TB enantiomers toward native α- and β-CDs were associated with significant differences between the structure of the related complexes in solution. In particular, the complex between TB enantiomers and α-CD was of the external type, whereas an inclusion complex was formed between TB enantiomers and β-CD. One of the possible structures of the complex between TB and heptakis(2,3-di-O-acetyl)-β-CD (HDA-β-CD) was quite similar to that of TB and β-CD, although the chiral recognition pattern and enantioselectivity of TB complexation with these two CDs were very different.