CD Cavity Size Research Articles

Enantioseparation of alanyl-phenylalanine analogs by capillary electrophoresis using negatively charged cyclodextrins as chiral selectors

The separation of the ll- and dd-enantiomers of the dipeptides Ala-Phe, Ala-phenylglycine (Phg), Ala-homoPhe, Ala-β-Phe, Gly-Phe and β-Ala-Phe was studied by capillary electrophoresis in the presence of negatively charged α-, β- and γ-cyclodextrin (CD) derivatives. Analysis was performed under standardized conditions in fused-silica capillaries at pH 2.5, 3.5 and 5.3. All analyte enantiomers could be separated at pH 2.5 under at least one of the experimental conditions. Especially β-CD derivatives proved to be effective chiral selectors. The enantiomer migration order depended on CD cavity size and substituent type, while peptide structure had only a minor effect. Upon increasing the pH from 2.5 to 5.3, reversal of the enantiomer migration order was observed frequently. Investigation of the apparent and, in the case of randomly substituted CDs, averaged complexation constants and mobilities of the diastereomeric peptide enantiomer-CD complexes indicated that in most cases the migration order in the presence of sulfated α-, β- and γ-CD and heptakis(6-O-sulfo)-β-CD could be explained by the stronger binding of the second migrating analyte by the CD at pH 2.5. However, in few cases the weaker bound enantiomer migrated second, which could be attributed to the higher mobility of the respective CD complexes. At pH 5.3, similar data were obtained for sulfated β-CD and heptakis(6-O-sulfo)-β-CD, i.e. the strength of the complexes determined the migration order for some peptides, while the migration sequence was based on the apparent (and averaged) mobility of the diastereomeric analyte-CD complexes in other cases.

Highly permeable and antifouling TFC FO membrane prepared with CD-EDA monomer for protein enrichment

The development of thin film composite (TFC) membrane with a high flux, a good fouling resistance and superior rejections remains a challenging task for membrane researchers, due to the inherent permeability-selectivity trade-off of the polymeric selective layer. In this work, highly permeable TFC membranes with excellent fouling resistance are developed by employing hydrophilic pore-containing monomers – ethylenediamine (EDA)-substituted cyclodextrins (α, β, γ-CD-EDA) in interfacial polymerization. Effects of CD-EDA type on the surface properties, pore size, separation performance and antifouling properties of TFC_CD-EDA membranes are investigated by considering the differences in CD cavity size and EDA substitution degree. Superior FO flux up to 26–28 LMH (0.5 M Na2SO4 draw solution) and exceptional antifouling properties with relatively low flux reduction (< 20%) and high flux recovery rate (> 91%) can be achieved by TFC_CD-EDA membranes, owing to the unique structure of CD-EDA with the intramolecular cavity and abundant hydrophilic hydroxyl groups. Furthermore, TFC_β-CD-EDA membrane is applied for the enrichment of high-concentration BSA solution by taking advantage of its high flux, low reverse draw solute leakage and excellent fouling resistance. The obtained high BSA enrichment efficiency and high-quality BSA suggest a great potential of TFC_CD-EDA membrane in this aspect.

Enantioseparation of Flavanoids, Isoxazolines, Dansyl Amino Acids and β-Blockers on Native and Phenylcarbamoylated α, β and γ-Cyclodextrin Chiral Stationary Phases

In this study, a series of native and p-methylphenylcarbamoylated cyclodextrin chiral stationary phases (CD-CSPs) were developed based on α, β and γ-cyclodextrin via ether linkage. The as-prepared CSPs were characterized by FTIR, solid-state C13 NMR, thermogravimetric analysis and elemental analysis. Their enantioseparation properties were comprehensively investigated by using high performance liquid chromatography (HPLC) with various racemates including flavanoids, isoxazolines, dansyl amino acids and β-blockers. The effects of CD cavity size and CD functionalities on the enantioseparation results were evaluated in detail. The correlation between analyte structures and their chiral resolution were also investigated. A reference chart has been proposed for quick choice of CD-CSPs for enantioseparation of specific racemates.

Cyclodextrin-peptide conjugates for sequence specific DNA binding.

Synthetic models of bZIP transcription factors have been developed with the capability of specific DNA recognition. Our design is based on the CuAAC mediated conjugation of basic region Leucine Zipper peptides to different derivatives of α, β and γ-cyclodextrins equipped with azide functionalities. Thorough optimization of reaction conditions allowed convergent and simultaneous conjugation of two long unprotected cationic peptides to cyclodextrin-bis azide derivatives. The resulting constructs were shown to specifically recognize their cognate DNA sequence with nM affinities. In comparison with previously developed TF models, the derivatives described here combine the enhanced DNA binding capabilities with an easy and convergent synthetic route.

Host–Guest Chemistry of Dendrimer–Cyclodextrin Conjugates: Selective Encapsulations of Guests within Dendrimer or Cyclodextrin Cavities Revealed by NOE NMR Techniques

In this study, G5 PAMAM dendrimer and α-, β-, γ-cyclodextrin (CD) conjugates were synthesized. Host-guest behaviors of the conjugates toward five guest molecules including sodium methotrexate (MTX), amantadine hydrochloride (ADH), sulfamethoxazole (SMZ), sodium deoxycholate (SDC), and sodium dodecyl sulfate (SDS) were analyzed by NOE NMR techniques. Among the five guest molecules, ADH only binds with β-CD in G5-β-CD, SDC shows higher priority to localize within the cavity of γ-CD in G5-γ-CD, while MTX exhibits selective encapsulation within the cavities of G5 dendrimer in G5-α-CD. SDS has high binding affinity with α-CD in G5-α-CD but forms a precipitate in the complex solution. SMZ shows simultaneous encapsulation within CDs (α-, β-, and γ-CD) or G5 in the presence of the three conjugates. The host behavior of G5-CD conjugates depends on CD cavity size, guest size, and hydrophobicity. The results obtained in this study are helpful in the optimization of dendrimer-CD conjugate-based drug delivery systems.

Bilirubin adsorption properties of water-soluble adsorbents with different cyclodextrin cavities in plasma dialysis system

In this study, we explored the use of α-, β- or γ-cyclodextrin (CD)-grafted polyethyleneimine (PEI) as water-soluble adsorbent for removing excess plasma bilirubin. To evaluate the bilirubin-binding capacity of these adsorbents, bovine serum albumin (BSA) solution or plasma with high level of bilirubin were dialyzed against CD-PEI-spiked dialysate. In BSA solution with an initial biliurbin concentration of 171.5 mg/L, α-CD-PEI, β-CD-PEI and γ-CD-PEI achieved adsorption capacities of 2.5, 5.8 and 3.8 mg/g, respectively. In a plasma dialysis system, 45.6% of bilirubin (260 mg/L) was removed from 200 mL plasma by 1 L dialysate spiked with 10 mg/mL β-CD-PEI, which was significantly higher than that removed by the same volume of BSA-spiked dialysate ( P < 0.05), demonstrating the strong bilirubin-binding ability of β-CD-PEI. The key feature of bilirubin adsorption was related to the CD functional group, not the PEI matrix. Subsequent molecular docking study indicated that the size of CD cavity could affect the affinity energy of CD–bilirubin complex. The cavity of β-CD was most suitable for accommodating the pyrrole rings of bilirubin. The inclusion complex of bilirubin and β-CD in the molar ratio of 1:2 was more logical in terms of affinity energy. All the results demonstrated the potential of β-CD-PEI (water-soluble adsorbent) as an effective agent for removing of bilirubin from plasma in dialysis system.

Novel cyclodextrin chiral stationary phases for high performance liquid chromatography enantioseparation: Effect of cyclodextrin type

Three novel chiral stationary phases (CSPs) were prepared by regioselective chemical immobilization of mono(6 A- N-allylamino-6 A-deoxy)perphenylcarbamoylated (PICD) α-, β-, and γ-cyclodextrins (CDs) onto silica support via hydrosilylation. Their enantioseparation properties in high performance liquid chromatography (HPLC) were evaluated with a large spectrum of racemates including flavanone compounds, β-adrenergic blockers, amines and non-protolytic compounds. The effect of CD's cavity size on enantioseparation abilities was studied and discussed. The results indicated that CD's surface loading at silica support played an important role in the enantioseparation on these CSPs under normal-phase conditions while inclusion phenomena contributed the major driving force under reverse-phase conditions. As expected, α-PICD demonstrated the best resolutions towards flavonone and most aromatic alcohols under normal-phase conditions with the highest surface loading; while Fujimura's competitive inclusion model can be applied to explain the better enantioseparations towards β-adrenergic blockers, amines and non-protolytic compounds with α- and β-PICD CSPs. γ-PICD CSP showed superior enantioseparation ability for sterically encumbered analytes like flavanone compounds under both normal-phase and reversed phase conditions.

Butanol isomer separation using polyamide–imide/CD mixed matrix membranes via pervaporation

Abstract Mixed matrix membranes (MMMs) comprising polyamide–imide (PAI) and α-, β- or γ-cyclodextrin (CD) have been investigated experimentally and computationally for isomeric n-butanol/tert-butanol (n-BuOH/t-BuOH) separation via pervaporation. Consistent with molecular simulation, experimental results show that the CD inclusion ability and butanol discrimination ability are dependent on both CD cavity size and butanol molecular size. The PAI membrane incorporated with α-CD has the smallest cavity and has the highest discrimination ability for the n-BuOH/t-BuOH pair but with a low butanol flux. The mixed matrix membrane embedded with γ-CD has the lowest selectivity and the highest flux. The PAI/β-CD membrane has a comparable selectivity and flux, and exhibits preferential sorption and diffusion selectivity toward n-BuOH. A maximum separation factor of 1.53 with a corresponding flux of 4.4 g/m 2 h are obtained at an optimal β-CD loading of 15 wt%. Further increments in the CD content eventually lead to a decrease in separation performance because of CD agglomeration and severe phase separation. To better understand the influence of CD on the separation performance of mixed matrix membranes, SEM, FTIR and XRD have been employed for membrane characterizations. The effect of n-butanol/t-butanol ratio in the feed composition has also been studied. It is found that both flux and separation factor decrease with increasing n-butanol content in the feed. The decline is attributed to the change in total vapor pressure at the upstream and the mutual drag effect of isomeric butanol molecules.

Electrospinning of functional poly(methyl methacrylate) nanofibers containingcyclodextrin-menthol inclusion complexes

Electrospinning of nanofibers with cyclodextrin inclusion complexes (CD-ICs) is particularlyattractive since distinct properties can be obtained by combining the nanofibers withspecific functions of the CD-ICs. Here we report on the electrospinning of poly(methylmethacrylate) (PMMA) nanofibers containing cyclodextrin-menthol inclusion complexes(CD-menthol-ICs). These CD-menthol-IC functionalized nanofibers were developed withthe purpose of producing functional nanofibers that contain fragrances/flavors with hightemperature stability, and menthol was used as a model fragrance/flavor material. ThePMMA nanofibers were electrospun with CD-menthol-ICs using three type of CD:α-CD,β-CD,and γ-CD. Direct pyrolysis mass spectrometry (DP-MS) studies showed that the thermalevaporation of menthol occurred over a very high and a broad temperature range(100–355 °C) for PMMA/CDmenthol-IC nanowebs, demonstrating the complexation of menthol with the CDcavity and its high temperature stability. Furthermore, as the size of CD cavity increased in the orderα-CD<β-CD<γ-CD, the thermal evolution of menthol shifted to higher temperatures, suggesting thatthe strength of interaction between menthol and the CD cavity is in the orderγ-CD>β-CD>α-CD.

Cavity size effect on ICT-dual emission of p-(N,N-dimethylamino)-2-styrylquinoline: complexation with cyclodextrin derivatives

The effect of cyclodextrin inclusion complex formation on the intramolecular charge transfer (ICT) of the included 4-N,N-dimethylamino-2-strylquinoline (2-StQ-NMe2) has been studied in detail. 2-StQ-NMe2 in presence of α-, β-, γ- and HP-α- and Hp-β-CDs predominantly exhibits ICT fluorescence predominantly than the emission from locally excited state, whereas in presence of HP-γ-CD the later is observed. In presence of α-CD, 2:1 complexation of the 2-StQ-NMe2 is observed in addition to 1:1 complexation. The observed results are explained by the CD cavity size and an active role for the secondary hydroxyl groups present in the wider rim of the CD cavity and also which finds support from absorption, emission, lifetime and molecular modeling studies.

Factors Controlling the Complex Architecture of Native and Modified Cyclodextrins with Dipeptide (Z-Glu-Tyr) Studied by Microcalorimetry and NMR Spectroscopy: Critical Effects of Peripheral Bis-trimethylamination and Cavity Size

Complex stability constant (K), standard free energy (DeltaG degrees ), reaction enthalpy (DeltaH degrees ), and entropy change (TDeltaS degrees ) for 1:1 inclusion complexation of the diastereomeric dipeptides Z-d/l-Glu-l-Tyr (Z = benzyloxycarbonyl) and its component amino acids (Z-d/l-Glu and N-Ac-Tyr) with native alpha-, beta-, and gamma-cyclodextrins (CDs) and A,X-modified bis(6-trimethylammonio-6-deoxy)-beta-CDs (AX-TMA(2)-beta-CDs) were determined in buffer solution (pH 6.9) at T = 298.15 K by isothermal titration microcalorimetry. Concurrent NMR spectral examinations revealed that the penetration mode and the resulting complex architecture are dramatically altered by the peripheral modification and also by the CD's cavity size. Upon complexation of the ditopic Z-Glu-Tyr guest, native alpha- and beta-CDs preferentially bind the Z's phenyl group, whereas AX-TMA(2)-beta-CDs predominantly include the Tyr's phenol moiety. In contrast, native gamma-CD includes both of the aromatic moieties simultaneously in the same cavity. Furthermore, for isomeric AB-, AC, and AD-TMA(2)-beta-CDs, an inversion of enantioselectivity and a switching of the penetration mode were observed, critically depending on the position of TMA substituents.

Combination of cyclodextrins and polymeric surfactants for chiral separations.

A cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) method was applied to the enantioseparation of three binaphthyl derivatives using neutral CDs (i.e., beta- and gamma-CD) in combination with various chiral amino acid-based polymeric surfactants (PSs). Both the D- and L-configurations of poly(sodium N-undecanoyl alaninate), poly(sodium N-undecanoyl leucinate), and poly(sodium N-undecanoyl valinate) (poly(L-SUV)) were synthesized. The retention behavior of the three binaphthyl derivatives under optimum electrophoretic conditions using a single chiral additive (PS or CD) is discussed. In addition, the effect of CD cavity size and stereochemical configuration of polymeric surfactants on selectivity (alpha) and resolution (Rs) was investigated. The enantioseparation of (+/-)1,1'-binaphthyl-2,2'-diamine gave a reversal of enantiomeric order when using beta-CD in combination with any of the three D-configuration PS. However, better enantioseparation is obtained when using the corresponding L-configuration PS with beta-CD. A reversal of migration order (RMO) for the enantiomers of (+/-)1,1'-bi-2-naphthol was observed upon the addition of 10 mM gamma-CD to poly(L-SUV). However, no RMO of (+/-)1,1'-bi-2-naphthol was seen when either beta-CD or gamma-CD was combined with D-PS. The enantiomers of (+/-)1,1'-binaphthyl-2,2'-diyl hydrogen phosphate showed little enantioselective behavior toward the PS alone. However, combined D- or L-PS and beta-CD or gamma-CD systems gave increased Rs and alpha values. The chiral recognition of binaphthyl derivatives observed resulting from the various combinations of two chiral selectors is discussed.

The cavity size effect on the fluorescence properties of 4′-dimethylaminoacetophenone complexed with cyclodextrins

Abstract Fluorescence properties of excited 4 ′ -dimethylaminoacetophenone (DMAAP) complexed with α-, β-, and γ-cyclodextrins (CDs) were studied by means of steady state and time-resolved laser spectroscopy. The 1:2 DMAAP–α-CD and 1:1 DMAAP–β-CD complexes exhibited dual fluorescence in neutral aqueous solutions while only the fluorescence from the locally excited state was observed in the case of DMAAP complexed with γ-CD. The CD cavity size effect on the excited state dynamics of DMAAP–CD complexes was further discussed. It revealed that polarity effect introduced by the hydrophobic cavity is more important in controlling of the photochemistry of DMAAP than the restriction of molecular motion inside the CD cavity.

Effects of the Host Cavity Size and the Preparation Method on the Physicochemical Properties of Ibuproxam-Cyclodextrin Systems

The effect of cyclodextrin (Cd) complexation on ibuproxam (IBUX) dissolution properties was studied by evaluating both the influence of Cd cavity size and the preparation method used for obtaining solid inclusion complexes. Binary systems of IBUX with natural Cds, prepared using different techniques (kneading, sealed-heating, spray-drying), were studied by differential scanning calorimetry (DSC), hot-stage microscopy (HSM), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and their dissolution behavior was evaluated according to the dispersed amount method. The nature and the dissolution performance of the end product appeared to be related to both steric factors of host molecule and preparation method of the solid system. The αCd cavity size was less suitable for accommodating the IBUX molecule, whereas spray-drying and sealed-heating methods led to a true inclusion complex of IBUX in the βCd and γCd cavity. In contrast, the kneading method did not lead in any case to a real inclusion complex. Spray-dried systems with βCd and γCd were the most effective in achieving the enhancement of the IBUX dissolution rate.

Molecular Nanotube Aggregates of β- and γ-Cyclodextrins Linked by Diphenylhexatrienes

Linked by strings of diphenylhexatriene (DPH) molecules, beta- and gamma-cyclodextrins (CDs) can form nanotube aggregates that contain as many as approximately 20 betaCDs (20 nanometers long) or approximately 20 to 35 gammaCDs (20 to 35 nanometers long). Nanotube formation was indicated in solution, by fluorescence anisotropy and light scattering results, and on graphite surfaces, by scanning tunneling microscopy. Tubes were not observed for the smaller alphaCDs. Molecular modeling shows that CD cavity size and the rodlike DPH structure are key factors in nanotube formation. Spectra generated by proton nuclear magnetic resonance indicate the inclusion of DPH in the interior of the CDs and formation of nanotubes in betaCDs and gammaCDs only. The photophysical properties of DPH are affected by its arrangement into a one-dimensional array within the CD nanotube, possibly because of exciton formation.