Β-cyclodextrin In Aqueous Solution Research Articles

Unusual Solubility Properties of Polymethacrylamides as a Result of Supramolecular Interactions with Cyclodextrin

Clearing things up. Hydrophobic polymers that undergo complex formation with β-cyclodextrin in aqueous solution display reversible thermosensitive solubility. Supramolecular effects lead to a new kind of LCST behavior (LCST=lower critical solution temperature), which is evident from clouding and clearing points at defined temperatures (see picture). The polymer was synthesized by free-radical polymerization of the complexed monomer in water.

Molecular dynamics in aqueous solutions of β-cyclodextrin

Water molecule mobility in ion-containing and nonionic aqueous solutions of β-cyclodextrin was studied by quasielastic neutron scattering (QENS). The total self-diffusion coefficients and their components corresponding to the contributions from collective (Lagrange type) and single-particle (jump diffusion) parts of molecular motions were determined. From the data obtained, one can conclude that the molecular mobility of free water in nonionic aqueous solutions of β-cyclodextrin with guest molecules (2-aminopyridine) proceeds by a single-particle mechanism. The addition of Pb 2+ ions into the solution leads to increase in self-diffusion coefficients and growth of a bound water fraction.

Spectroscopic studies of inclusion complexes of 1-naphthol-4-sulfonate with β-cyclodextrin in aqueous solution

The photophysical properties of 1-naphthol-4-sulfonate (1N4S) in some solvents and in aqueous β-cyclodextrin solution have been investigated. The effect of β-cyclodextrin on the fluorescence quantum yield and on the proton transfer is examined. Fluorescence measurements show 1:1 inclusion of 1N4S in the β-cyclodextrin cavity with an association constant of 108 M −1. NMR studies are used to study the inclusion phenomena and to provide information on the geometry of 1N4S inside the cavity of β-cyclodextrin.

Anion Binding to a Ferric Porphyrin Complexed with Per-O-methylated β-Cyclodextrin in Aqueous Solution

5,10,15,20-Tetrakis(4-sulfonatophenyl)porphinato iron(III) (Fe(III)TPPS) forms a very stable 1:2 complex with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TMe-beta-CD), whose iron(III) center is located at a hydrophobic cleft formed by two face-to-face TMe-beta-CD molecules. Various inorganic anions (X(-)) such as F(-), Cl(-), Br(-), I(-), N(3)(-), and SCN(-) coordinate to Fe(III)TPPS(TMe-beta-CD)(2) to form five-coordinate high-spin Fe(III)TPPS(X)(TMe-beta-CD)(2), while no coordination occurs with ClO(4)(-), H(2)PO(4)(-), NO(3)(-), and HSO(4)(-). Except for F(-), none of the anions investigated coordinate to Fe(III)TPPS in the absence of TMe-beta-CD due to extensive hydration to the anions as well as to Fe(III)TPPS. The present system shows a high selectivity toward the N(3)(-) anion. The thermodynamics suggests that Lewis basicity, hydrophilicity, and shape of an X(-) anion are the main factors to determine the stability of the Fe(III)TPPS(X)(TMe-beta-CD)(2) complex.

NMR spectroscopy of inclusion complex of d-(-)-chloramphenicol with β-cyclodextrin in aqueous solution

1HNMR spectroscopic study in D 2O of mixtures of d-(-)-chloramphenicol (guest), present in two tautomeric forms in solution, and β-cyclodextrin (host) revealed the formation of 1:1 inclusion complex in which aromatic ring of the guest is tightly held by the host cavity. There seems no discrimination between the aromatic rings of two tautomers by the host.

Ultrasonic relaxation due to inclusion complex of amino acid by β-cyclodextrin in aqueous solution

Ultrasonic absorption coefficients in the frequency range of 0.8-95 MHz were measured in aqueous solutions of L-methionine or L-norleucine (guest) in the presence and absence of beta-cyclodextrin (beta-CD, host) at 25 degrees C. A single relaxational absorption was observed only in the solutions containing the guest and host. The ultrasonic relaxation was attributed to a perturbation of a chemical equilibrium associated with an interaction between beta-CD and the amino acid to form the host-guest complex. The kinetic and thermodynamic parameters in the system of L-norleucine with beta-CD were determined from the concentration dependence of the relaxation frequency and the maximum absorption per wavelength. Because of the concentration independence of the relaxation frequency in L-methionine system with beta-CD, the equilibrium constant and the standard volume change of the complexation reaction were estimated first from the concentration dependence of maximum absorption per wavelength, and subsequently the rate constants were calculated with the help of the estimated equilibrium constant and the observed relaxation frequency. The results obtained in this study were compared with those for systems of beta-CD with other amino acids or alcohols having comparable hydrophobicity.

Multimodal inclusion complexes of ampicillin with β-cyclodextrins in aqueous solution

The inclusion complexation of ampicillin (ABPC) with β-cyclodextrin (βCD) and 2-hydroxypropyl-β-cyclodextrin (HPCD) in aqueous solution has been investigated by microcalorimetry, NMR spectrometry and molecular dynamics simulation (MDS). The heat of reaction of the complexation decreased as the pH value increased. ABPC and β-cyclodextrins formed one or two types of inclusion complexes by hydrophobic interactions and the complexation significantly depended on the species of ABPC based on the pH values of the solutions. Two different types of inclusion complexes with a 1:1 stoichiometry were realized for the cation species of ABPC in the strong acid solution. In the first type of inclusion with higher association constants of (6.0–10)×10 3 M −1, the penam ring of ABPC was inserted in the cyclodextrin cavity, whereas in the second type with lower association constants of 1.0×10 3 M −1, the phenyl ring seemed to penetrate into the cavity. The β-lactam ring of ABPC was included in both types to be protected from the acid-catalyzed hydrolysis. The zwitterion and anion species of ABPC formed only one type of inclusion complex with β-cyclodextrins, where the phenyl ring and the penam ring were included, respectively. These association constants and enthalpic changes were smaller than those for the first type inclusion complex of the cation species. These results indicate that the inclusion complexes of ABPC with β-cyclodextrins would be useful to the drug delivery system.

Global and distribution analysis of fluorescence decays and spectrofluorimetric determination of stoichiometry and association constant of the inclusion complex of 2-amino-5,6-dimethyl-benzimidazole with β-cyclodextrin

The steady state and time-resolved fluorescence study of 2-amino-5,6-dimethyl-benzimidazole (ADBI) have been studied in aqueous solution of β-cyclodextrin (β-CD). The fluorescence decays were analyzed by global analysis and distribution analysis in order to get insight about the inclusion process. The fluorescence lifetime of ADBI is increased in β-CD and an enhancement of the emission, is observed, together with negligible changes in the energy of ADBI in β-CD. The experimental data show that β-CD reacts with ADBI to form a 1:1 host–guest complex with association constant was determined to be 2074±77 M −1. Both global analysis and distribution analysis of the fluorescence decays support the formation of only 1:1 inclusion complex. AM1 calculation shows that the size of ADBI was appropriate for good insertion within the β-CD cavity and the inclusion of ADBI inside the β-CD cavity should takes place from the side of the amino group substituent.

Molecular dynamics simulations of β-cyclodextrin in aqueous solution

Molecular dynamics (MD) simulations of β-cyclodextrin (β-CD) have been carried out in aqueous solution at 300 K over a period of about 200 ps using Tripos force field. The atomic trajectories obtained by these simulations have been analysed by means of the occurrence of hydrogen bonds. The MD simulations lead to an association of seven water molecules into the β-CD cavity which is in a good agreement with X-ray crystallography experiments. This demonstrates that the force field used in the simulations is able to reproduce the experimentally observed hydrophilic–hydrophobic characteristics of β-CD molecule.

Diffusion coefficients of sodium dodecylsulfate in aqueous solutions and in aqueous solutions of β-cyclodextrin

Differential diffusion coefficients have been measured of sodium dodecylsulfate (SDS) in aqueous solutions of β-cyclodextrin (β-CD) at 298.15 K over the concentration range 0.001 M to 0.0817 M using a conductimetric cell and an automatic apparatus to follow the diffusion. The cell uses an open ended capillary method, while a conductimetric technique is used to follow the diffusion process by measuring the resistance of a solution inside the capillaries, at various recorded times. The β-CD is known to for strong 1:1 complexes with SDS, and the effect of this on the diffusion of this electrolyte was investigated. The presence of β-cyclodextrin can influence the diffusion coefficients of sodium dodecylsulfate both above and below the critical micelle concentration (cmc) of this surfactant. For concentrations of β-cyclodextrin of 0.001 mol dm−3 the behaviour of the diffusion of SDS in aqueous solutions is the same in the absence or the presence of β-cyclodextrin. In contrast, when the β-CD concentration is 0.016 mol dm−3 we obtain diffusion coefficients higher than those obtained in aqueous solutions. Further, we do not observe the dramatic decrease in diffusion normally found at the cmc of the surfactant. These results are interpreted in terms of the effect of incorporation of dodecylsulfate chains inside the cyclodextrin cavities.

Determination of budesonide R(+) and S(−) isomers in pharmaceuticals by thin-layer chromatography with UV densitometric detection

A new HPTLC separation and determination of budesonide R(+) and S(−) isomers by densitometry metry at 245 nm has been developed. A cellulose-coated TLC plate and a 1% aqueous solution of β-cyclodextrin with methanol as mobile phase were used for the separation. Under the conditions established high sensitivity was achieved, with detection limits 34.64–43.72 ng, as well as a high recovery 98.76–103.60% for the individual isomers. Validation of the method confirmed the high precision and accuracy of the results.

Molecular Recognition Kinetics of Leucine and Glycyl-Leucine by β-Cyclodextrin in Aqueous Solution in Terms of Ultrasonic Relaxation

Ultrasonic absorption coefficients in the frequency range of 0.8−95 MHz were measured in aqueous solution of leucine and glycyl-leucine in the presence and absence of β-cyclodextrin (β-CD) at 25 °C. A single relaxational absorption was found in both solutions although it was not observed in the absence of β-CD. The cause of the relaxation was attributed to a perturbation of a chemical equilibrium associated with an interaction between β-CD and the amino acid or the dipeptide. The rate and thermodynamic constants for the association and dissociation reaction of the complex in the system of glycyl-leucine and β-CD were determined from the concentration dependence of the relaxation frequency and the maximum absorption per wavelength. On the other hand, another analysis was applied for the system with leucine and β-CD to calculate the rate and thermodynamic constants due to the indistinguishable concentration dependence of the relaxation frequency. Therefore, first the equilibrium constant was estimated from ...

The self-association of the drug acemetacin and its interactions and stabilization with β-cyclodextrin in aqueous solution as inferred from NMR spectroscopy and HPLC studies

Strongly concentration dependent, 1H NMR chemical shifts of the non-steroidal anti-inflammatory drug acemetacin sodium salt (sodium {[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetoxy}acetate), were observed in aqueous solution. Self-titration and nOe experiments, point to a self-association model where stacking takes place via the indole portion of the drug. In addition, conformational isomerism (atropisomerism) of the anti to syn form was confirmed. Further increase of the concentration eventually led to stable chemical shifts and nearly simultaneous appearance of microcrystals. In the presence of βCD, 1:1 inclusion complexation occurred through the p-chlorobenzoyl part of the drug, whereas with excess βCD the indole part seemed to participate to a minor degree. The anti isomer is suggested to be involved in the inclusion process. In addition, aggregation of acemetacin was also evident, as competing with the conformational and inclusion equilibria. The present case demonstrates that many competitive processes are simultaneously active in a seemingly simple system. The measurements were strongly dependent upon the pH and use of buffered solutions was mandatory. Finally, for the quantitative analysis of acemetacin in the presence of βCD, a special HPLC method was developed. The stability of the drug, studied by the identification of the degradation products and the pseudo-first order rate of hydrolysis, was found to be unaffected by the presence of βCD.

Temperature Induced Crystallization Transition in Aqueous Solutions of β-Cyclodextrin, Heptakis(2,6-di-O-methyl)-β-cyclodextrin (DIMEB), and Heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TRIMEB) Studied by Differential Scanning Calorimetry

Methylated cyclodextrins were investigated to shed light on their solubility behavior in water where they exhibit a negative temperature coefficient, contrasting the positive temperature coefficient of unmodified cyclodextrins. Both heptakis(2,6-di-O-methyl)-β-cyclodextrin (DIMEB) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TRIMEB) show two different conditions of crystallization. At low temperatures around 18 °C, highly hydrated clathrates are formed, whereas, at high temperatures around 60−70 °C, DIMEB crystallizes as an anhydrate and TRIMEB as a monohydrate. The crystallization at high temperature is driven by entropy gain of water to compensate for the positive enthalpy change associated with this crystallization process, as could be shown by differential scanning calorimetry experiments in H2O and D2O.

Synthesis and coordination properties of functionalized β-cyclodextrins. Thermodynamic of proton and copper(II) complexes of 3A-deoxy-3A-(2-methylaminopyridine)-2A( S),3A( R)-β-cyclodextrin in aqueous solution

The 3A-deoxy-3A-(2-methylaminopyridine)-2A( S),3A( R)-β-cyclodextrin (CDampy3) was synthesized and characterized by NMR spectroscopy. The proton and copper(II) complex formation and stability of this new β-cyclodextrin derivative were determined by potentiometric and calorimetric investigations, carried out in aqueous solution at 25 °C and I=0.1 mol dm −3 (KNO 3). The Δ H° and Δ S° values allowed to bring to light the role of the hydrogen bond between the amine and the hydroxyl groups in the basicity decrease of NH group of this 3-functionalized β-cyclodextrin. The comparison between the log K values of copper(II) complexes with CDampy3 and those of 6-deoxy-6-(2-methylaminopyridine)-β-cyclodextrin (CDampy6) allowed to determine the donor atoms involved in the coordination to metal ion. The high stability constant of [Cu(CDampy3)] 2+ in comparison with [Cu(CDampy6)] 2+ was attributed to the involvement of the OH groups in the binding to copper(II) ion.

Resonance Rayleigh scattering technology as a new method for the determination of the inclusion constant of β-cyclodextrin

The interaction of procaine hydrochloride and β-cyclodextrin in aqueous solution was studied using resonance Rayleigh scattering technology. The molar ratio of the inclusion complex was 1:1 established by spectrophotometry. The resonance Rayleigh scattering technology was first applied in the determination of the β-cyclodextrin inclusion constant. The inclusion constant of procaine hydrochloride–β-cyclodextrin complex K f is 1.23×10 2 and 1.27×10 2 l mol −1 for method I and 1.15×10 2 and 1.21×10 2 l mol −1 for method II. These determination results were in correspondence with the results of the spectrophotometric and fluorescence methods. Therefore, the resonance Rayleigh scattering method can be used as a new technology for the determination of the inclusion constant.

Thermodynamics of the interactions of ascorbic acid with α- and β-cyclodextrins in aqueous solutions

As found by calorimetry and densimetry, ascorbic acid forms a molecular 1:1 complex with α- but not with β-cyclodextrin in aqueous solution.

Calorimetric study of the molecular recognition of nucleic acid bases by β-cyclodextrin in aqueous solution

As found by calorimetry, β-cyclodextrin can recognise nucleic acid bases and their derivatives in aqueous solutions by forming inclusion complexes with only purine bases (adenine and caffeine).

Cyclodextrin-Induced Room-Temperature Phosphorescence of 1-Bromo-2-naphthol upon Formation of Ternary Complexes

The inclusion constant for the 1:1 binary complex between 1-bromo-2-naphthol and β-cyclodextrin in aqueous solution was determined by a spectrofluorimetric method. On the basis of MO calculations, a possible structure of this complex was proposed and compared with those formed by two related naphthol derivatives. After the addition of different alcohols (linear, branched, and cyclic) to the 1-bromo-2-naphthol–β-cyclodextrin solution, a significant enhancement of the room-temperature phosphorescence (RTP) was observed. Both the formation constants and stoichiometries of the formed ternary complexes were determined from RTP data with the use of the computational program EPSILON. It was verified that RTP was also induced by adding different apolar liquids (cyclohexane and 1,3-dibromopropane) as the third component instead of alcohols. Of all the examined compounds, cyclohexanol produced both the largest RTP signal and the more stable ternary complex. The RTP calibration graph for 1-bromo-2-naphthol in the presence of both β-cyclodextrin and cyclohexanol was linear for the range of concentrations between 0.6 and 4.0 μg mL−1 with a limit of detection of 0.2 μg mL−1, with a relative standard deviation ( n = 4) of 4%, for 2.2 μg mL−1.

Influence of the Preparation Method on the Physicochemical Properties of Tolbutamide/Cyclodextrin Binary Systems

Tolbutamide (TBM) was found to form an inclusion complex with β-cyclodextrin (β-CD) in solution and in solid state. Inclusion complex formation between tolbutamide and β-cyclodextrin in aqueous solution was studied by phase solubility and spectral shift methods. The apparent stability constant Ks calculated by these techniques, in water, were estimated as 195.7 and 236.5 M−1, respectively. The phase solubility studies revealed a BS-type diagram with an inclusion complex of 1:2 molar ratio. The solid inclusion complexes of TBM and β-CD were prepared at a molar ratio of 1:2 by kneading, coprecipitation, freeze-drying, and spray-drying methods. In addition, the physical mixture was prepared. Characterization of TBM:β-CD inclusion was performed using differential scanning calorimetry (DSC), Raman spectroscopy, and X-ray diffractometry and by application of a so-called ether wash method. All the inclusion systems investigated led to a significant improvement in the dissolution over free TBM, and the dissolution rate of the active material was observed to be independent of the preparation method.