Study on the inclusion interaction of ethyl violet with cyclodextrins by MWNTs/Nafion modified glassy carbon electrode

The interactions of ethyl violet (EV) with cyclodextrins (CDs) were investigated by Multi-wall carbon nanotubes/Nafion composite film modified glassy carbon electrode (MWNTs/Nafion/GCE). It was found that the MWNTs/Nafion composite film can effectively catalyze the electrode reaction of EV. The variation of the electrochemical behavior of EV upon the addition of CDs indicated the formation of the inclusion complexes of EV with β-CD, heptakis (2,3,6-tri-O-methyl)-β-CD (TM-β-CD), heptakis (2,6-di-O-methyl)-β-CD (DM-β-CD), hydroxypropyl-β-CD (HP-β-CD), and carboxymethyl-β-CD (CM-β-CD). The stoichiometry ratios of EV and the above five CDs were found to be 1:1. The inclusion ability obeyed the order: CM-β-CD > HP-β-CD > TM-β-CD > DM-β-CD > β-CD. The results showed that the modified β-CDs exhibited stronger binding ability than native β-CD, especially the charged CM-β-CD, which implied that the inclusion capacity depends on not only size matching and hydrophobicity but also electrostatic interaction. ¹HNMR spectra and molecule mechanics calculations suggested that EV was included into the cavity of β-CD from the wider side.     

Complexation of Ketoconazole by Native and Modified Cyclodextrins

Complexation of ketoconazole (KET), a broad-spectrum antifungal drug, with β- and γ-cyclodextrins (CDs), heptakis (2,6-di-O-methyl)-β-CD (2,6-DM-β-CD), heptakis (2,3,6-tri-O-methyl)-β-CD (TM-β-CD), 2-hydroxypropyl-β-CD (2HP-β-CD) and carboxymethyl-β-CD (CM-β-CD) was studied. The stability constants were determined by the solubility method at pH = 6 and for 2,6-DM-β-CD and CM-β-CD at pH = 5. At pH = 6, the stability constants increased in the order: TM-β-D < γ-CD < 2HP-β-CD < β-CD < CM-β-CD < 2,6-DM-β-CD. At pH = 5, due to the increased ionization of KET, the stability constant with CM-β-CD increased and with 2,6-DM-β-CD decreased. For complexes of KET with 2HP-β-CD and 2,6-DM-β-CD, the thermodynamic parameters of complexation were determined from the temperature dependence of the corresponding stability constants. For β–γ and TM-β-CD complexes, calculations using HyperChem 6 software by the Amber force field were carried out to gain some insight into the host–guest geometry.     

Spectroscopic characterisation of the inclusion complexes between the antifungal drugs naftifine and terbinafine and cyclodextrins

The complexation of naftifine (NF) and terbinafine (TB) with cyclodextrins (CDs) has been investigated by UV/visible and ¹H NMR spectroscopy, ROESY techniques and also ESI-MS. Both drugs form 1:1 inclusion complexes with all the CDs tested except with α-CD, as deduced from the Benesi–Hildebrand plots and confirmed by ESI-MS and NMR spectroscopy (Job plot method). The K ₁₁ values for NF decrease in the order β-CD > methylated β-CD > 2-hydroxypropyl-β-CD >γ-CD. The determination of the enthalpy and entropy provides information about the main driving forces in the process. The stability constants of the complexes NF–β-CD, TB–β-CD and TB–γ-CD determined by ¹H NMR spectroscopy are in agreement with the values obtained by UV. For TB–β-CD, the value is higher, due to the fact that the length of the TB aliphatic chain allows a deeper inclusion of the naphthalene group inside the corresponding β-CD molecule, according to the 2D ROESY experiments.     

Investigation of the inclusion of the herbicide cycluron in native cyclodextrins by X-ray diffraction,nuclear magnetic resonance spectroscopy and isothermal titration calorimetry

The formation of inclusion complexes between the native cyclodextrins (CDs) and the urea herbicide cycluron has been investigated both in solution and in the solid state. Single-crystal X-ray structures of both the uncomplexed guest and the β-CD·cycluron complex were determined while powder X-ray diffraction was used to confirm complexation between γ-CD and cycluron in the solid state. Solution-state complexation between the herbicide and α-, β- and γ-CD was established using ¹H NMR spectroscopy and isothermal titration calorimetry (ITC). From the ¹H NMR spectroscopic studies 1:1 complex stoichiometry was indicated in all cases and association constant values (K) were determined as 228, 3254 and 155 for the complexes α-CD·cycluron, β-CD·cycluron and γ-CD·cycluron, respectively. Assigning a 1:1 host–guest ratio, the ITC technique produced K values of the same order as those determined using the spectroscopic method. The thermodynamic parameters ΔH, ΔS and ΔG obtained using ITC provide insights into the driving forces involved during complex formation.     

Study on the complexation of isoquercitrin with β-cyclodextrin and its derivatives by spectroscopy

The inclusion complexes of isoquercitrin (IQ) with cyclodextrins (CDs) including β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and dimethyl-β-cyclodextrin (DM-β-CD) have been investigated using the methods of steady-state fluorescence, UV-vis absorption and induced circular dichroism. The stoichiometric ratio of the three complexes was found to be 1:1 and the stability constants (K) were estimated from spectrofluorometric titrations, as well as the thermodynamic parameters. Maximum inclusion ability was measured in the case of DM-β-CD due to the increased hydrophobicity of the host cavity, followed by HP-β-CD and β-CD. The effect of pH on the complexation process was also quantitatively assessed. IQ exists in different molecular forms depending on pH and β-CDs were most suitable for inclusion of the neutral form of IQ. The phase-solubility diagrams obtained with β-CD, HP-β-CD and DM-β-CD were all classical A_L type. And DM-β-CD provided the best solubility enhancement, 12.3-fold increase compared to 2.8- and 7.5-fold increase for β-CD and HP-β-CD. The apparent stability constants obtained from the solubility data at 25 °C were comparable with those obtained from the fluorescence assays. Moreover, ¹H NMR was carried out, which revealed that the IQ favorably inserted into the inner cavity from the chromone part instead of the phenyl part, which was in agreement with molecular modeling studies.     

Host–guest complexation of a nitroheterocyclic compound with cyclodextrins: a spectrofluorimetric and molecular modeling study

Nitroheterocyclic compounds (NC) were candidate drugs proposed for Chagas disease chemotherapy. In this study, we investigated the complexation of hydroxymethylnitrofurazone (NFOH), a potential antichagasic compound, with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), Hydroxypropyl-β-cyclodextrin (HP-β-CD), Dimethyl-β-cyclodextrin (DM-β-CD) and γ-cyclodextrin (γ-CD) by fluorescence spectroscopy and molecular modeling studies. Hildebrand–Benesi equation was used to calculate the formation constants of NFOH with cyclodextrins based on the fluorescence differences in the CDs solution. The complexing capacity of NFOH with different CDs was compared through the results of association constant according to the following order: DM-β-CD > β-CD > α-CD > HP-β-CD > γ-CD. Molecular modeling studies give support for the experimental assignments, in favor of the formation of an inclusion complex between cyclodextrins with NFOH. This is an important study to investigate the effects of different kinds of cyclodextrins on the inclusion complex formation with NFOH and to better characterize a potential formulations to be used as therapeutic options for the oral treatment of Chagas disease.     

Complex Formation of Hematoporphyrin with Cyclodextrins and 1,1′-Diheptyl-4,4′-bipyridinium Dibromide in Aqueous Solutions

At around 5×10^-6?mol?dm^-3 of hematoporphyrin (HP), an HP dimer exists as well as an HP monomer. The equilibrium constant for the dimerization of HP in pH 10.0 buffer has been evaluated to be 1.70×10⁵?mol^-1?dm³ from the HP concentration dependence of the absorption spectrum. In aqueous solution, HP forms 1:1 inclusion complexes with β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD). The fluorescence of HP is significantly enhanced by the addition of CDs. From simulations of the fluorescence intensity changes, the equilibrium constants for the formation of the CD–HP inclusion complexes have been estimated to be 200, 95.7, and 938?mol^-1?dm³ for β-CD, γ-CD, and TM-β-CD, respectively. HP forms a 1:1 complex with 1,1′-diheptyl-4,4′-bipyridinium dibromide (DHB) in aqueous solution. In contrast to the addition of CDs, the HP fluorescence is significantly quenched by the addition of DHB. The equilibrium constant for the formation of the HP–DHB complex has been evaluated to be 1.98×10⁵?mol^-1?dm³ from the fluorescence intensity change of HP. The addition of DHB to an HP solution containing β-CD induces a circular dichroism signal of negative sign, indicating the formation of a ternary inclusion complex involving β-CD, HP, and DHB. In contrast, there is no evidence for the formation of a ternary inclusion complex of HP with DHB and TM-β-CD.     

Characterization of inclusion complex of vitamin E compound with 2,6-di-O-methylated β-cyclodextrin as the solubility enhancer and its kinetic determination for radical scavenging ability

The structure of the inclusion complex of α-tocopherol (vitamin E compound) with 2,6-di-O-methylated β-cyclodextrin (DM-β-CD) was characterized by 2D ROESY NMR measurements, suggesting that DM-β-CD includes the side-chain moiety of α-tocopherol. The inclusion complexation of DM-β-CD showed the usefulness of water solubilizer for the radical scavenging assay of vitamin E compounds in aqueous solution. Using the electron paramagnetic resonance (EPR) competitive spin trapping method, we determined the oxygen radical (RO^?) scavenging abilities of seven vitamin E compounds (tocopherols and tocotrienols), which were solubilized by DM-β-CD in water. The order of the RO^? radical scavenging abilities for vitamin E compounds solubilized by DM-β-CD are α- > β- ≈ γ- > δ-, which is in agreement with the oxidation potential values of antioxidants. It is noted that the RO^? radical scavenging abilities of tocotrienols are comparable to those of tocopherols. Based on the results, the mechanism of the antioxidant reaction of vitamin E compounds with the RO^? radical is discussed.     

Inclusion complexes of modified cyclodextrins with some flavonols

The inclusion complexes of four flavonols with modified cyclodextrins (CDs) have been investigated. The effect of heptakis (2,6-di-O-methyl) β-cyclodextrin (DM-β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on the aqueous solubility of flavonols, namely, galangin, kaempferol, quercetin, and myricetin was investigated, respectively. The increased solubility of all flavonols in the presence of CD was evidenced. The NMR experiment and molecular modeling studies showed that flavonols interact with each modified CD through different binding modes. Flavonols can complex with CDs largely by two binding modes. The first one is that B-ring of flavonols is oriented toward secondary rim of CD. The second one is that A-ring of flavonols is oriented toward secondary rim of CD. Whereas only the first mode was observed in DM-β-CD complexes, both the first and the second mode were observed in HP-β-CD complexes in this study.     

NMR spectroscopic characterization of inclusion complexes of hydroxy-substituted naphthalenes with native and modified β-cyclodextrins

The equilibrium constants (K) for the inclusion complexation of three kinds of β-cyclodextrins (β-CDs: native β-CD, heptakis(2,6-di-O-methyl)-β-CD, and 6-O-α-d-glucosyl-β-CD) with OH-substituted naphthalenes (2-naphthol, 2,3-dihydroxynaphthalene, and 2,6-dihydroxynaphthalene) were determined from the induced chemical shifts of NMR measurements for inclusion complexes: K = 188–1,250 mol^?1 dm³. The modified β-CDs form stable 1:1 inclusion complexes with OH-substituted naphthalenes, and the high stability of inclusion complexes of 2,6-dihydroxynaphthalene having a hydrophobic body and hydrophilic ends is shown. In addition, the structures of inclusion complexes were characterized by 2D ROESY NMR measurements. The differences in the structure of the inclusion complexes were observed for three kinds of naphthol guest molecules. Based on the results, the inclusion abilities enhanced by methylation of the OH groups at the CD rim or the side chain of branched β-CD are discussed.     

Kinetic studies on the thermal dissociation of β-cyclodextrin-cinnamyl alcohol inclusion complex

The stability of β-cyclodextrin-cinnamyl alcohol inclusion complex (β-CD·C₉H₁₀·8H₂O) was investigated using TG and DSC. The mass loss took place in three stages: the dehydration occurred between 50–120°C; the dissociation of β-CD·C₉H₁₀O occurred in the range of 210–260°C; and the decomposition of β-CD began at 280°C. The dissociation of β-CD·C₉H₁₀O was studied by means of thermogravimetry, and the results showed: the dissociation of β-CD·C₉H₁₀O was dominated by a two-dimensional diffusion process (D₂). The activation energyE was 161.2 kJ mol^?1, the pre-exponential factorA was 4.5×10¹³ min^?1. Cyclodextrin is able to form inclusion complexes with a great variety of guest molecules, and the interesting of studies focussed on the energy binding cyclodextrin and the guest molecule. In this paper, β-cyclodextrin-cinnamyl alcohol inclusion complex was studied by fluorescence spectrophotometry and infrared absorption spectroscopy, and the results show: the stable energy of inclusion complexes of β-CD with weakly polar guest molecules consists mainly of Van der Waals interaction.     

Inclusion complexes of cyclodextrins with 4-amino-1,8-naphthalimides (part 2)

Fluorescence spectroscopy was used to characterize inclusion compounds between 4-amino-1,8-naphthalimides (ANI) derivatives and different cyclodextrins (CDs). The ANI derivatives employed were N-(12-aminododecyl)-4-amino-1,8-naphthalimide (mono-C₁₂ANI) and N,N′-(1,12-dodecanediyl)bis-4-amino-1,8-naphthalimide (bis-C₁₂ANI). The CDs used here were α-CD, β-CD, γ-CD, HP-α-CD, HP-β-CD and HP-γ-CD. The presence of CDs resulted in pronounced blue-shifts in the emission spectra of the ANI derivatives, with increases in emission intensity. This behavior was parallel to that observed for the dyes in apolar solvents, indicating that inclusion complexes were formed between the ANI and the CDs. Mono-C₁₂ANI formed inclusion complexes of 1:1 stoichiometry with all the CDs studied. Complexes with the larger CDs (HP-β-CD, HP-γ-CD and γ-CD) were formed by inclusion of the chromophoric ANI ring system, whereas the smaller CDs (α-CD, HP-α-CD and β-CD) formed complexes with mono-C₁₂ANI by inclusion of the dodecyl chain. Bis-C₁₂ANI formed inclusion complexes of 1:2 stoichiometry with HP-β-CD, HP-γ-CD and γ-CD, but did not form inclusion complexes with α-CD, HP-α-CD and β-CD. The data were treated in the case of the large CDs using a Benesi-Hildebrand like equation, giving the following equilibrium constants: mono-C₁₂ANI:HP-β-CD (K ₁₁ = 50 M^?1), mono-C₁₂ANI:HP-γ-CD (K ₁₁ = 180 M^?1), bis-C₁₂ANI:HP-β-CD (K ₁₂ = 146 M^?2), bis-C₁₂ANI:HP-γ-CD (K ₁₂ = 280 M^?2).     

Study on the Supramolecular System of TAPP and Cyclodextrins by Spectroscopy

The ability of β-cyclodextrin (β-CD), γ-CD, hydroxypropyl-β-CD (HP-β-CD), trimethyl-β-CD (TM-β-CD), sulfurbutylether-β-CD (SBE-β-CD) and carboxymethyl-β-cyclodextrin (CM-β-CD) to break the aggregate of the meso-tetrakis(4-N-trimethylaminobenzyl)porphyrin (TAPP) and to form 2:1 inclusion complexes has been studied by absorption and fluorescence spectroscopy. The formation constants are calculated, respectively, by fluorimetry, from which the inclusion capacity of different CDs is compared and the inclusion mechanism of charged-β-CD (SBE-β-CD and CM-β-CD) is quite different from that of the parent β-CD. At lower pH, the complexation between TM-β-CD and H²TAPP²⁺ (the form of the diprotonated TAPP) hampers the continuous protonation of the pyrrole nitrogen of TAPP and the hydrophobic cavity may prefer to bind an apolar neutral porphyrin molecule. ¹HNMR data support the inclusion conformation of the porphyrin–cyclodextrin supramolecular system, indicating the interaction of the meso-phenyl groups of TAPP with the cavity of CDs. For this host–guest inclusion model, cyclodextrin being regarded as the protein component, which acts as a carrier enveloping the active site of heme prosthetic group within its hydrophobic environment, provides a protective sheath for the porphyrin, creating artificial analogues of heme-containing proteins. However, for TAPP, encapsulated within this saccharide-coated barrier, its photophysical and photochemical properties changed strongly.     

高效液相色谱手性流动相添加剂分离乳酸对映体

分别将β-环糊精、2,6－二甲基－β－环瑚精和2,3,6－三甲基－β－环糊精作为手性流动相添加剂,系统地研究了D,L-乳酸在反相HPLC系统中的拆分,考察了流动相种类,pH值和手性流动相添加剂的浓度对手性分离的影响,建立了甲基化β-环糊精动态手性固定相分离乳酸对映体的方法。     

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.     

Chemical and enzymatic synthesis of glycocluster having seven sialyl lewis X arrays using β-cyclodextrin as a key scaffold material

An efficient and practical method for the large-scale synthesis of an anti-inflammatory glycocluster having seven sialyl Lewis X (SLeX) residues was established on the basis of chemical and enzymatic strategy from β-cyclodextrin (β-CD) as a key starting scaffold material. A key intermediate, β-CD derivative having seven N-acetyl-d-glucosamine (GlcNAc) residues [(GlcNAc)₇CD], was prepared by a coupling reaction with heptakis 6-deoxy-6-iodo-β-cyclodextrin and sodium thiolate containing a GlcNAc residue. Subsequent sugar elongation reactions of (GlcNAc)₇CD proceeded smoothly by means of β-1,4-galactosyltransferase, α-2,3-sialyltransferase, and α-1,3-fucosyltransferase V in the presence of the corresponding sugar nucleotides (UDP-Gal, CMP-Neu5Ac, and GDP-Fuc) and allowed to give a mono-dispersed glycodendrimer (M_w=7924.5, calcd for C₃₀₁H₄₉₀N₂₁O₁₉₆S₇Na₇; MALDI-TOF MS, m/z 7946 [M+Na]⁺) that completely substituted with seven SLeX branches at C-6 positions in excellent overall yield (74%, 3 steps). Hyper-branched glycodendrimer, (SLeX)₇CD, exhibited highly amplified inhibitory effect on the interaction of E-selectin with SLeXn-BSA immobilized on the sensor chip by means of surface plasmon resonance method.     

Separation of enantiomers of norephedrine by capillary electrophoresis using cyclodextrins as chiral selectors: comparative CE and NMR studies

In this study, the enantiomer migration order (EMO) of norephedrine (NEP) in the presence of various CDs was investigated by CE. NMR and CE techniques were used to analyze the mechanism of the chiral recognition between NEP enantiomers and four CDs, i.e., native α-CD, β-CD, heptakis(2,3-di-O-acetyl-6-O-sulfo)-β-CD (HDAS-β-CD), and heptakis(2,3-di-O-methyl-6-O-sulfo)-β-CD (HDMS-β-CD). EMO was reversed in the presence of α-CD and β-CD, although only minor differences in the structures of the complexes formed between NEP and these CDs could be derived from rotating frame nuclear Overhauser experiments (ROESY). The complexes between the enantiomers of NEP and the sulfated CDs, HDMS-β-CD, and HDAS-β-CD, were substantially different. However, EMO of NEP was identical in the presence of these CDs. HDAS-β-CD proved to be the most suitable chiral selector for the CE enantioseparation of NEP.     

β-Cyclodextrin derivatives hybrid Fe3O4 magnetic nanoparticles as the drug delivery for ketoprofen

β-Cyclodextrin (β-CD) and its derivatives carboxymethyl-β-CD (CM-β-CD) and 2,6-dimethyl-β-CD (DM-β-CD) modified magnetic nanoparticles (CD-MNPs) were synthesized via layer-by-layer method. CDs grafted onto Fe₃O₄ MNPs were demonstrated by transmission electron microscopy, Fourier transform infrared and Zeta potential. Magnetic properties of CM-β-CD-MNPs, DM-β-CD-MNPs and β-CD-MNPs were characterized by vibrating sample magnetometer and the magnetic saturation values were 47, 46 and 44 emu g^?1, respectively. CD-MNPs as drug carriers were investigated by inclusion behavior and in vitro release using ketoprofen (KP) as a model drug. The maximum adsorption quantities of CM-β-CD-MNPs, DM-β-CD-MNPs and β-CD-MNPs for KP were 37.03, 7.63 and 25.12 mg g^?1, respectively, and the loading behaviors followed the Langmuir adsorption isotherm model with monolayer adsorption. The release profiles of KP released from KP-loaded CD-MNPs were rapid in initial 60 min and then gradually tend to level off, the release efficiency order was CM-β-CD-MNPs > β-CD-MNPs > DM-β-CD-MNPs, which was consistent with the order of inclusion capability. Therefore, the CD-MNPs were promising candidates for drug delivery.     

The effect of heavy metals on the anthracene–Me-β-cyclodextrin host–guest inclusion complexes

Anthracene was used to form an inclusion complex with methylated-β-cyclodextrin (Me-β-CD) in water. In aqueous Me-β-CD solution, typical fluorescence emission of anthracene was observed. Benesi–Hildebrand's method was used to obtain the stoichiometry of the anthracene–Me-β-CD complex. The Stern–Volmer quenching constants, K_sv, and fluorescence quantum yields were calculated according to changes in the fluorescence emission intensity of anthracene–Me-β-CD inclusion complexes by adding various amounts of Pb²⁺ and Cd²⁺ salts in water. The K_sv values and fluorescence quantum yields indicate that Pb²⁺ salts quench the anthracene–Me-β-CD inclusion complexes more efficiently than Cd²⁺ salts.     

Spectroscopic characterization of the binding and isomerization cycle of Brooker’s merocyanine with α-, β-, and γ-cyclodextrins

Complexes of Brooker’s merocyanine dye with α-, β- and γ-cyclodextrin (CD) have been characterized to determine the relative strength and thermodynamics of binding, as well as the effect of binding on the protolytic-photochemical isomerization cycle of the dye. It was found that the dye binds most tightly to β-CD, with a binding equilibrium constant of 430 M^?1, in agreement with previous results (Hamasaki et al. J. Incl. Phenom. Mol. Rec. Chem. 13, 349–359 (1992)), while α-CD and γ-CD complexes have a binding constant of approximately 110 M^?1 and 70 M^?1, respectively, determined using absorbance and fluorescence spectroscopy. The isomerization cycle for the dye in α- and γ-CD complexes was found to be the same as for the free dye. Complexation with β-CD, however, resulted in depressed trans-to-cis photoisomerization in acidic conditions followed by spontaneous cis-to-trans isomerization (with the addition of base). Thermodynamic results also indicated differences between α-CD (ΔS° = ?48 J K^?1) and β-CD (ΔS° =  +12 J K^?1) complexes. There was no temperature dependence observed for the γ-CD complexes. These results can be justified in terms of the location of the dye molecule within the cyclodextrin cavity for each of the complexes.