The complexation of flurbiprofen with β-cyclodextrin: a NMR study in aqueous solution

The complexation process between racemic flurbiprofen and β-cyclodextrin in solution was investigated by 1D and 2D proton NMR spectroscopy. In the presence of β-cyclodextrin, the aromatic protons of flurbiprofen were the most affected, suggesting a strong involvement of the phenyl groups in the inclusion mechanism. The stoichiometry of the complex was determined by the method of continuous variation, using the chemical induced shifts of both host and guest protons. The association constant, K_a of the obtained complex was calculated and found to be 2483.8 M^?1. On the other hand, signals belonging to the protons associated with the carboxyl group are split in the presence of β-cyclodextrin indicating enantiomeric differentiation. Rotating frame NOE spectroscopy, (ROESY), was used to ascertain the solution geometry of the host–guest complex. The result suggested that the flurbiprofen molecule fully penetrates the β-cyclodextrin cavity with the carboxyl group protruding from the primary hydroxyl side and the phenyl group close to the secondary rim.     

Extrathermodynamic relations in the binding of charged and neutral substrates to sulfobutylether-β-CDs (SBE-β-CDs) and a 2-hydroxypropyl-β-CD (HP-β-CD)

The thermodynamics of binding of various neutral, cationic and anionic substrates to β-cyclodextrin, a hydroxylpropyl-β-cyclodextrin (HP_4M-β-CD) and three sulfobutyl-β-cyclodextrins with varying degrees of total substitution (SBE_1M-β-CD, SBE_7M-β-CD, and SBE_12M-β-CD) were determined by estimating binding constants, using a UV spectrophotometric technique, and temperature variation. linear free energy relation (LFER) plots and enthalpy–entropy Compensation (EEC) plots provided insight into the mechanisms of complexation as did carbon T ₁ relaxation times using NMR. LFER plots for charged molecules with HP_4M-β-CD deviate from the neutral substrates suggesting differences in interaction modes. LFER plots for SBE_7M-β-CD show that cationic substrates surprisingly fall within the same linear relationship for neutral substrates while anionic substrates deviate. The EEC plots for HP_4M-β-CD show the largest loss of motion and degree of desolvation upon complexation. The interaction with SBE_1M-β-CD was similar to that for β-CD. SBE_7M-β-CD, and SBE_12M-β-CD EEC plots are similar with the least loss of motion upon complex formation, suggesting a more organized and less flexible structure. This is supported by the T ₁ relaxation times for SBE_1M-β-CD, SBE_7M-β-CD, and SBE_12M-β-CD, which show a critical distance at which the mobility of the side chain is reduced to form an extended cavity. No such evidence was seen with HP_4M-β-CD, although the effect of varying of hydroxypropyl substitution was not studied.     

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.     

β-Hydroxylation of anthraquinone derivatives with benzaldehyde oxime as a source of hydroxyl group

Hydroxyanthraquinones are of significant interest due to their broad spectrum of biological activity, coloring properties and synthetic applications. Here, we describe a mild and convenient method for β-hydroxylation of anthraquinone derivatives that can be used during late stages of modifications. The scheme is based on the Miller-Loudon-Snyder reaction, which uses benzaldoxime as a source of a hydroxyl group. The influence of different leaving groups and neighboring substituents at the anthraquinone core on reaction rate and yield has been evaluated. A series of β-hydroxyanthraquinone derivatives was synthesized using the developed approach.     

Synthesis of a novel β-cyclodextrin derivative with high solubility and the electrochemical properties of ferrocene-carbonyl-β-cyclodextrin inclusion complex as an electron transfer mediator

A facile strategy for preparing water-soluble β-cyclodextrin derivative, carbonyl-β-cyclodextrin, was developed by partial oxidation of β-cyclodextrin. The solubility of carbonyl-β-cyclodextrin was greatly enhanced due to the breaking of intramolecular hydrogen bond network of β-cyclodextrin. Ferrocene was included into the cavity of carbonyl-β-cyclodextrin to form Fc-carbonyl-β-cyclodextrin inclusion complex. The electrochemical properties of Fc-carbonyl-β-cyclodextrin were studied. The Fc-carbonyl-β-cyclodextrin complex exhibited high solubility and was shown to be good electrochemical probe and efficient mediator for bioelectrocatalysis of glucose oxidase. The bioelectrocatalytic efficacy of Fc-carbonyl-β-cyclodextrin complex opened up homogeneous applications of ferrocene in amperometric biosensor systems.     

Aggregation of cyclodextrins: An explanation of the abnormal solubility ofβ-cyclodextrin

-,- and -Cyclodextrins have been shown to exist as aggregates in solution bound together by a network of hydrogen bonds. Removal of this network by ionisation of the hydroxyl groups leads to a greatly increased solubility and removal of aggregation. The presence of aggregates in solution of structure breaking solutes in which the solubility of-cyclodextrin is greatly enhanced, leads to a proposal that the abnormally low solubility of-CD may be explained by the presence of aggregates and the unfavourable interaction of these aggregates with the hydrogen bonded structure of water.     

A comparative study of inclusion complexes of flunarizine with alpha (α-CD) and beta-cyclodextrin (β-CD)

A detailed NMR (¹H, COSY, and ROESY) spectroscopic study of complexation of Flunarazine (FL) with α- and β-CD was carried out. ¹H NMR titration studies confirmed the formation of FL/α-CD and FL/β-CD complexes as evidenced by chemical shift variations of the proton resonances of both the CDs and FL. The stoichiometry of the complexes was determined to be 1:2 (FL/α-CD) and 1:1 (FL/β-CD) and overall binding constants were also calculated. It was confirmed with the help of ROESY spectral data that only one of the F-substituted aromatic ring and phenyl ring penetrate the α-CD cavity while both F-substituted aromatic rings as well as phenyl ring penetrates the β-CD cavity during complexation. The binding modes of FL/CD cavity interactions derived from ROESY experimental data show that the resulting complex of FL with β-CD possesses better induced fit interaction as compared to α-CD, which is responsible for the enhanced molecular stability with β-CD in comparison to α-CD. The mode of penetration of guest into the CD cavity and structures of the complexes has been established.     

Enhanced solubility of fullerene (C60) in water by inclusion complexation with cyclomaltononaose (δ-CD) using a cogrinding method

The solubilizing effects of cyclomaltononaose (δ-CD), a cyclic oligosaccharide composed of nine α-1,4-linked d-glucose units, on C₆₀ were investigated by using a ball-milling method based on a solid–solid mechanochemical reaction. The complex between C₆₀ and δ-CD was characterized by UV–VIS spectrometry, ¹³C-NMR, and fast atom bombardment mass spectrometry (FAB-MS). Coloration of the C₆₀/δ-CD system was yellowish-brown in aqueous solution, and the UV–VIS spectrum was in agreement with that of C₆₀ in hexane solution. The ¹³C-NMR spectrum of C₆₀/δ-CD system in aqueous solution revealed the presence of free δ-CD and dissolved C₆₀ giving one sharp peak at 144.4 ppm, which was close to that reported for C₆₀ in organic solvents. The FAB-MS spectrum of the C₆₀/δ-CD system showed a negative ion peak corresponding to the molecular weight of a complex between two δ-CDs and one C₆₀. Moreover, the phase solubility diagram of C₆₀ with δ-CD at 10 °C was classified as the Bs-type, resulting in a stoichiometric ratio of 1:2 (C₆₀:δ-CD), in agreement with the stoichiometry obtained from FAB-MS. These findings suggest that the solubilization of C₆₀ in water was due to complex formation of C₆₀ with δ-CD and that the stoichiometric ratio of the complex was 1:2 (C₆₀:δ-CD).     

Enhancement of aqueous solubility of tricyclic acyclovir derivatives by their complexation with hydroxypropyl-β-cyclodextrin

Solubilities of tricyclic acyclovir derivatives in buffered aqueous solutions of hydroxypropyl-β-cyclodextrin (HP-β-CD) at pH 5.5 and 7.0 were determined at 25 and 37 °C. Complexation of these compounds with HP-β-CD resulted in a noticeable increase of their solubility; nevertheless it was limited to tricyclic derivatives of acyclovir carrying an aryl substituent. Combination of ¹H NMR and DSC techniques demonstrated the existence of inclusion complexes between acyclovir derivatives and HP-β-CD. The stability constants, estimated using the Higuchi–Connors method, were found in the range of 10–100 M⁻¹. Additionally, the pK _a values at 25 °C and molar extinction coefficients in aqueous buffered solutions were also determined for all studied compounds.     

Riboflavin as a green sorbent in dispersive micro-solid-phase extraction of several pesticides from fruit juices combined with dispersive liquid–liquid microextraction

A vortex-assisted dispersive micro-solid-phase extraction procedure using a new and green sorbent was developed as a simple, fast, and efficient sample preparation method for the extracting five pesticides in several fruit juice samples. In this study, for the first time, riboflavin was used as an efficient sorbent. A few milligrams of riboflavin was directly added into the aqueous solution containing the analytes to adsorb them. After adsorption the analytes, they were desorbed and more concentrated by a dispersive liquid–liquid microextraction procedure. The influence of several effective parameters such as amount of riboflavin, pH, vortex time, eluent nature and volume, and extraction solvent type and volume on the extraction efficiency was investigated. In optimal conditions, linear ranges of the calibration curves were broad. The limits of detection and quantification were attained in the ranges of 0.56–1.5  and 1.9–0.52 ng mL⁻¹, respectively. The proposed method demonstrated to be suitable for concurrent extraction of the studied pesticides in various fruit juice samples with high enrichment factors (320–360) and precision (relative standard deviation ≤7.8% for intra- [n = 6] and interday [n = 4] precisions at a concentration of 25 ng mL⁻¹ of each pesticide).     

Synthesis of a kind of geminal imidazolium ionic liquid with long aliphatic chains

A novel geminal imidazolium ionic liquid with long hydrocarbon group,1,4-bis(3-tetradecylimidazolium-1-yl)butane bromide was synthesized and an efficient synthesized method was introduced detailedly.Its structure was determined by FT-IR,~1H NMR and elemental analysis.     

Development of a dispersive liquid–liquid microextraction (DLLME) method coupled with GC/MS as a simple and valid method for simultaneous determination of phthalate metabolites in plasma

Phthalates are ubiquitous environmental contaminants, and frequent biological monitoring of their metabolites (as toxic species of phthalates in human body) is highly recommended. A novel dispersive liquid–liquid microextraction (DLLME) coupled with Gas Chromatography–Mass Spectrometry (GC-MS) has been developed for the determination of seven phthalate metabolites in human plasma for the first time. Plasma proteins were efficiently precipitated by adding of 0.2mg dry trichloroacetic acid to 10 mL plasma samples, incubation and centrifuging. For DLLME, a mixture of extraction solvent (chlorobenzene, 10 µL) and dispersive solvent (acetonitrile, 750 µL) were rapidly injected into 5.0 mL aqueous sample for the formation of cloudy solution, the analytes in the sample were extracted into the fine droplets of chlorobenzene. After extraction, phase separation was performed by centrifugation and the enriched analytes in the sedimented phase were subjected to GC-MS analysis. All important parameters affecting DLLME performance were investigated and optimised. Under the optimum extraction condition, the method yields a linear calibration curve for all target analytes in the concentration range from 5 to 5000 ng mL^?1. The limits of detection and relative standard deviations for all phthalate metabolites were between 1.21–2.09 ng mL^?1 and 4.8–6.8%, respectively. This is a very simple, rapid and reproducible method, which requires low volume of sample and toxic solvents.     

Extraction of cadmium with trilaurylamine–kerosine through a flat-sheet-supported liquid membrane

Cadmium has been extracted as a chloride complex through a flat-sheet-supported liquid membrane (SLM), using the tertiary amine Alamine 304-1 (mainly trilaurylamine or TLA) in kerosine.The typical permeability of the membrane was 1.1×10⁻⁶ m s⁻¹. The rate limiting step is diffusion through the membrane. The cadmium loading of the extractant at the feed–membrane interface is high. Trilaurylammonium chloride crystallizes at the surface of the membrane above 0.2 M TLA. This salt blocks the pores and lowers the extraction rate up to a factor of 3. Apart from this blocking effect, the permeability through the membrane is described well with the presented model, using physically realistic parameter values. When the precipitation can be minimized, the system has good potentials for the extraction of cadmium chloride complexes.     

Determination of carbohydrates in tobacco by pressurized liquid extraction combined with a novel ultrasound-assisted dispersive liquid–liquid microextraction method

A novel derivatization-ultrasonic assisted-dispersive liquid–liquid microextraction (UA-DLLME) method for the simultaneous determination of 11 main carbohydrates in tobacco has been developed. The combined method involves pressurized liquid extraction (PLE), derivatization, and UA-DLLME, followed by the analysis of the main carbohydrates with a gas chromatography-flame ionization detector (GC-FID). First, the PLE conditions were optimized using a univariate approach. Then, the derivatization methods were properly compared and optimized. The aldononitrile acetate method combined with the O-methoxyoxime-trimethylsilyl method was used for derivatization. Finally, the critical variables affecting the UA-DLLME extraction efficiency were searched using fractional factorial design (FFD) and further optimized using Doehlert design (DD) of the response surface methodology. The optimum conditions were found to be 44 μL for CHCl₃, 2.3 mL for H₂O, 11% w/v for NaCl, 5 min for the extraction time and 5 min for the centrifugation time. Under the optimized experimental conditions, the detection limit of the method (LODs) and linear correlation coefficient were found to be in the range of 0.06–0.90 μg mL⁻¹ and 0.9987–0.9999. The proposed method was successfully employed to analyze three flue-cured tobacco cultivars, among which the main carbohydrate concentrations were found to be very different.