Ultrasonic study of the molecular encapsulation and the micellization processes of dodecylethyldimethylammonium bromide-water solutions in the presence of β-cyclodextrin or 2,6-di-o-methyl-β-cyclodextrin

Aqueous solutions of -cyclodextrin (-CD) or 2,6-di-o-methyl--cyclodextrin (DM--CD) and dodecylethyldimethylammonium bromide (D₁₂EDMAB) have been studied from speed of sound (u) data at 298.15 K, using a pulse-echo-overlap technique. The molecular encapsulation process of the surfactant monomer into the cyclodextrin cavity and its effect in the micellization process of the surfactant have been analyzed from theu measurements: I) as a function of [D₁₂EDMAB] in the presence of several initial cyclodextrin concentrations (-CD or.DM--CD); II) as a function of [cyclodextrin] (-CD or DM--CD), for an initial micellar solution of D₁₂EDMAB and; III) as a function of the [cyclodextrin]/[surfactant] stoichiometric concentrations. Both inclusion complexes formed (-CDD₁₂EDMAB) and (DM--CDD₁₂EDMAB) have stoichiometries of 11, and their association constantK have been determined using a model proposed in this work, based on the additivity of the different contributions of the involved species to the speed of sound. The apparent critical micellar concentration, cmc^*, of D₁₂EDMAB is found to increase linearly upon the addition of cyclodextrin (-CD or DM--CD). The free surfactant concentration in the micellar region, [D₁₂EDMAB]_f, decreases in the presence of -CD and slightly increases in the presence of DM--CD. The influence of the parcial methylation of the -cyclodextrin (-CDDM--CD) and of the polar head of the surfactant (D₁₂TAB D₁₂EDMAB) on the complextion and micellar parameters are also discussed.Supplementary material available: Tables of speed of sound (14 pages) are available from the authors.     

Triclosan-loaded with high encapsulation efficiency into PLA nanoparticles coated with β-cyclodextrin polymer

The purpose was to prepare triclosan-loaded polylactic acid nanoparticles containing β-cyclodextrin polymer shell, evaluate triclosan release from the particles using Franz diffusion cells and to study the stability of the particles in presence of a model protein, bovine serum albumin. The nanoparticles were prepared by a solvent displacement process. The nanoparticles were characterized by their size, encapsulation efficiency and morphology. They were of spherical shape with hydrodynamic diameter of about 100 or 200 nm depending on the polylactic acid used. Their high encapsulation efficiency (~90%) indicated that triclosan is easily incorporated into the nanoparticles. The nanoparticles displayed slow and sustained triclosan release patterns (diffusion coefficient about 10^?22 m²/s) and the β-cyclodextrin polymer coating was stable under simulated physiological conditions. All these data indicated that these novel core–shell nanoparticles might provide a promising carrier system for controlled release of triclosan and other hydrophobic drugs after systemic administration.     

Spectrofluorimetric study and determination of desipramine in the presence of β-cyclodextrin

The native fluorescence intensity of desipramine was enhanced in the presence of β-cyclodextrin in aqueous solution. The inclusion complex formation between these compounds was studied by spectrofluorimetry. A stable complex with a 2: 1 stoichiometry of β-cyclodextrin to desipramine was formed (logβ₂ = 9.29 ± 0.01). In the presence of an optimum concentration of β-cyclodextrin, the fluorescence intensity was linearly proportional to desipramine concentration in the range of 0.1–100 μg/mL (7.2 × 10^?7?1.0 × 10^?4 M) with a limit of detection of 7 × 10^?8 M. The method was successfully applied to the detection of desipramine in its tablets.     

Computational investigation of enol/keto chloramphenicol with β-cyclodextrin

PM3 and ONIOM2 were carried out to investigate the structures and properties for the inclusion complexes of chloramphenicol tautomers into β-cyclodextrin (at 1:1 stoichiometry). Two possible orientations into host cavity were considered for both enol and keto chloramphenicol. The PM3 results gives that B orientation is more preferred for enol and keto form, the preference is of 0.63 and 1.67 kcal/mol respectively. This preference is greater in the case of ONIOM2 calculations. Finally, the chemical shifts (ppm) of free and complexed chloramphenicol were calculated at B3LYP/6-31G(d) by (GIAO method) and compared with experimental data taken from the literature.     

The effect of β-cyclodextrin on the properties of cetyltrimethylammonium bromide micelles

The effect of ß-cyclodextrin (ß-CD) on cetyltrimethylammonium bromide (CTAB) micellar properties was studied by the determination of the diffusion coefficient, D. When the CTAB micelles have a spherical structure, D firstly increased and then remained unchanged, while the micellar aggregation number, N, decreased with the addition of ß-CD. When the CTAB concentration was less than the first critical micellar concentration, CTAB molecules could be included into ß-CD cavities with the molar ratio of CTAB to ß-CD being about 1:1. However, when the CTAB concentration was higher than the first critical micellar concentration, mixed spherical micelles were formed with the molar ratio of CTAB to ß-CD being 9:1.     

A quartz crystal microbalance study of β-cyclodextrin self assembly on gold and complexation of immobilized β-cyclodextrin with adamantane derivatives

Quartz crystal microbalance (QCM) was used to study the self-assembly of per-6-thio-β-cyclodextrin (t₇-βCD) on gold surfaces, and the subsequent inclusion interactions of immobilized βCD with adamantane-poly(ethylene glycol) (5,000 MW, AD-PEG), 1-adamantanecarboxylic acid (AD-C) and 1-adamantylamine (AD-A). From a 50 μM solution of t₇-βCD in 60:40 DMSO:H₂O, a t₇-βCD layer was formed on gold with surface density of 71.7 ± 2.7 pmol/cm², corresponding to 80 ± 3% of close-packed monolayer coverage. Gold sensors with immobilized t₇-βCD were then exposed alternately to six different concentrations of AD-PEG, 500 μM AD-C or 500 μM AD-A aqueous solutions for association, and water for dissociation. Association of AD-PEG conformed to a Langmuir isotherm, with a best fit equilibrium constant K = 125,000 ± 18,000 M⁻¹. For AD-C and AD-A, association (k _a ) and dissociation (k _d ) rate constants were extracted from kinetic profiles by fitting to the Langmuir model, and equilibrium constants were calculated. The parameters for AD-C were found to be: k _a = 100 ± 5 M⁻¹ s⁻¹, k _d = 110 (±18) × 10⁻⁴ s⁻¹, and K = 9,400 ± 1,700 M⁻¹. For AD-A, k _a = 58 ± 6 M⁻¹ s⁻¹, k _d = 154 (±7) × 10⁻⁴ s⁻¹, and K = 3,800 ± 400 M⁻¹. The results demonstrate the utility of QCM as a tool for studying small molecule surface adsorption and guest–host interactions on surfaces. More specifically, the kinetic and thermodynamic data of AD-C, AD-A, and AD-PEG inclusion with immobilized t₇-βCD form a basis for further surface association studies of AD-X conjugates to advance surface sensory and coupling applications.     

A study on the inclusion complexation of 3,4,5-trihydroxybenzoic acid with β-cyclodextrin at different pH

Effect of β-cyclodextrin (β-CD) on the absorption and fluorescence spectra of 3,4,5-trihydroxybenzoic acid (THB) have been studied buffer solutions of different pHs (pH ~1, pH ~7 and pH ~10). The study reveals that in all the above pHs THB forms 1:1 inclusion complex. The hydroxyl groups are present in the interior part of the β-CD cavity and carboxyl group is present in the hydrophilic part of the β-CD cavity. Dual luminescence is observed at pH ~1 and pH ~7 solutions which shows that intramolecular charge transfer present at these pH. The broad spectral maximum at pH ~10 indicates that intramolecular proton transfer is present in THB.     

Investigation on the inclusion behaviour of baicalein with β-cyclodextrin and derivatives and their antioxidant ability study

The formation of the complexes of baicalein (Ba) with β-cyclodextrin (β-CD) and β-CD derivatives (HP-β-CD and Me-β-CD) was studied by UV–vis absorption spectroscopy, fluorescence method, nuclear magnetic resonance spectroscopy and phase-solubility measurement. The solid–inclusion complexes of Ba with CDs were synthesised by the co-precipitation method. The characterisations of the solid–inclusion complexes have been proved by infrared spectra and differential scanning calorimetry. Experimental conditions including the concentration of various CDs and media acidity were investigated in detail. The results suggested that the inclusion ratio of HP-β-CD with Ba was the highest among the three kinds of CDs. The binding constants (Ks) of the inclusion complexes were determined by fluorescence method and phase-solubility measurement. Kinetic studies of DPPH√ with Ba and CDs complexes were also done. The results indicated that the Ba/HP-β-CD complex was the most reactive form.     

Influence of β-cyclodextrin on the protolytic and complexing ability of p-aminobenzoic acid

UV spectroscopy was used to study the protolytic properties and determine the ionization constants of p-aminobenzoic acid in the presence of β-cyclodextrin. Formation of supramolecular structures of 1: 1 composition was established. Stability constants of the β-cyclodextrin-p-aminobenzoic acid inclusion complex were calculated, as were the thermodynamic parameters (ΔG°, ΔH°, and ΔS°) of its formation. The complexing process between β-cyclodextrin and p-aminobenzoic acid was found to occur spontaneously in the temperature range under investigation while being accompanied by energy liberation and leading to a reduction in the system’s entropy.     

Combined computational and experimental study on the inclusion complexes of β-cyclodextrin with selected food phenolic compounds

Phenolic compounds, such as caffeic acid, trans-ferulic, acid and p-coumaric acid that are commonly found in food products, are beneficial for human health. Cyclodextrins can form inclusion complexes with various organic compounds in which the physiochemical properties of the included organic molecules are changed. In this study, inclusion complexes of three phenolic compounds with β-cyclodextrin were investigated. The complexes were characterized by various analytical methods, including nuclear magnetic resonance (NMR) spectroscopy, Fourier IR (FT-IR) spectroscopy, mass spectrometry, differential scanning calorimetry, and scanning electron microscopy. Results showed that the phenolic compounds used in this study were able to form inclusion complexes in the hydrophobic cavity of β-cyclodextrin by non-covalent bonds. Their physicochemical properties were changed due to the complex formation. In addition, a computational study was performed to find factors that were responsible for binding forces between flavors and β-cyclodextrin. The quantum-mechanical calculations supported the results obtained from experimental studies. Thus, ΔH_f for the complex of p-coumaric acid and β-cyclodextrin has been found as ??11.72 kcal/mol, which was about 3 kcal/mol more stable than for inclusion complexes of other flavors. Energies of frontier orbitals (higher occupied molecular orbital (HOMO) and lower unoccupied molecular orbital (LUMO)) were analyzed, and it was found that H-L gap for the complex of p-coumaric acid and β-cyclodextrin had the largest value (8.19 eV) in comparison to other complexes, which confirmed the experimental findings of the most stabile complex.

     

Inclusion of Paracetamol into β-cyclodextrin nanocavities in solution and in the solid state

We report on steady-state UV-visible absorption and emission characteristics of Paracetamol, drug used as antipyretic agent, in water and within cyclodextrins (CDs): β-CD, 2-hydroxypropyl-β-CD (HP-β-CD) and 2,6-dimethyl-β-CD (Me-β-CD). The results reveal that Paracetamol forms a 1:1 inclusion complex with CD. Upon encapsulation, the emission intensity enhances, indicating a confinement effect of the nanocages on the photophysical behavior of the drug. Due to its methyl groups, the Me-β-CD shows the largest effect for the drug. The observed binding constant showing the following trend: Me-β-CD>HP-β-CD>β-CD. The less complexing effectiveness of HP-β-CD is due to the steric effect of the hydroxypropyl-substituents, which can hamper the inclusion of the guest molecules. The solid state inclusion complex was prepared by co-precipitation method and its characterization was investigated by Fourier transform infrared spectroscopy, 1H NMR and X-ray diffractometry. These approaches indicated that Paracetamol was able to form an inclusion complex with CDs, and the inclusion compounds exhibited different spectroscopic features and properties from Paracetamol.     

Effects of solvent, pH and β-cyclodextrin on the fluorescent behaviour of lomustine

Fluorescent behaviour of lomustine, a DNA cross-linking agent, was investigated in different solvents, pH and in the presence of β-cyclodextrin (β-CD). The solvents in which fluorescence spectra were observed play a major role in determining the spectral intensity of fluorophore, since it was found to exhibit new fluorescent properties essentially influenced by intermolecular interactions, particularly by intermolecular H-bonding formed with solvents. The pH-dependence profile was typically U-shape with a maximum at pH between 3.51 and 6.58. It was corroborated that the fluorescence emission band of lomustine is significantly intensified in the presence of β-CD. From the changes in the fluorescence spectra, it was concluded that β-CD forms a 1:1 inclusion complex with lomustine and its association constant was calculated.     

Calculation study on complex formation of catechins with β-cyclodextrin using density function theory

Journal of Inclusion Phenomena and Macrocyclic Chemistry - The inclusion of catechins with cyclodextrin (CD) is performed for the purpose of improving the water solubility and reducing the...     

Computational insights about the dynamic behavior for the inclusion process of deprotonated and neutral aspirin in β-cyclodextrin

A high-efficiency microwave irradiation (MW) assisted protocol was proposed to synthesize series SPE-β-CD with specific degree of substitution (DS) in the sodium hydroxide solution. This protocol provided an eco-friendly way to modify the cyclodextrins with bulky sulfopropyl substituent on the purpose of avoiding organic solvents and high quantities of thermal energy. Temperature and energy distribution became more uniform under the new method accordingly. Therefore, not only the reaction time reduced significantly from over 20 h to a few hours, but also the DS increased up according to ¹H NMR spectroscopy, MS and elemental analysis results. Most importantly, the effects of reaction parameters on DS were compared both under MW method and conventional heating method, and were sufficiently studied to guarantee the aforementioned results could be better reproduced and DS of products could become more specific through the synthesis process. Products structures were characterized by FT-IR, DSC, and ¹³C NMR spectroscopy.     

Conductivity studies of the molecular encapsulation of sodium perfluoroctanoate byβ-cyclodextrin derivatives

The molecular encapsulation of sodium perfluoroctanoate (SPFO) by hydroxypropyl--cyclodextrin (HP--CD) or 2,6-di-O-methyl--cyclodextrin (DM--CD) has been analyzed by measuring the conductivity in solution of the ternary systems formed by CD + SPFO + H₂O. The studies were carried out at 25 °C using a fully computerized electrical conductivity technique. The measurements were made as a function of CD concentration at various non-micellar concentrations of SPFO, and as a function of CD and SPFO concentrations with [CD]/[SPFO] constant at stoichiometric ratio. The inclusion complexes, HP--CD-SPFO and DM--CD-SPFO, were characterized through the stoichiometry, which has been found to be 1 : 1 in both cases, and the binding constants, which have been evaluated from the conductivity data with a model proposed by us considering the variation of the ionic molar conductivities with the concentration and the association of the surfactant counterion to the inclusion complex. The resultingK values indicate that the interaction between the CD cavity and the monomeric SPFO is strong and similar in both cases.     

Kinetic studies on the thermal dissociation of the inclusion complex of β-cyclodextrin with cinnamic aldehyde

The stability of the inclusion complex of -CD with cinnamic aldehyde was investigated by means of TG and DSC. The mass loss takes place in three stages: dehydration occurs at 50–120°C; dissociation of -CD·C₉H₈O proceeds in the range 200–260°C; and decomposition of -CD begins at 280°C. The kinetics of the dissociation of -CD·C₉H₈O was studied by means of thermogravimetry both at constant temperature and with linearly increasing temperature. The results demonstrate that the dissociation of -CD·C₉H₈O is dominated by a one-dimensional diffusion process. The activation energyE is 160 kJ mol^–1, and the pre-exponential factorA is 5.8×10¹⁴ min^–1. Scanning electron microscope observations and the results of crystal structure analysis are in good agreement with those of thermogravimetry.     

Characterization and mechanism study of micrometer-sized secondary assembly of β-cyclodextrin

We herein report a β-cyclodextrin-based secondary assembly (β-CD SA) obtained from an aqueous solution. It was found that the addition of a very small amount of organic molecule 2-phenyl-5-(4-diphenylyl) 1,3,4-oxadiazole (PBD) into an aqueous solution of 10 mM β-CD led to the formation of a micrometer-sized rodlike SA, which made the mixture turbid immediately. After careful characterization, the structure and the formation mechanism of the β-CD SA were suggested. PBD first induces β-CDs to form rigid nanotubes through head-to-head or tail-to-tail routes. Using the "solid" nanotubes as recrystallization centers, other β-CDs assembled to channel in the c axis direction and hexagonally aligned in the b axis direction, leading to the formation of a β-CD SA. In the β-CD SA, most of the β-CDs were not occupied by PBD. In the course of formation , intermolecular hydrogen-bonding plays a prominent role. The results reported herein would be helpful in constructing cyclodextrin-based architectures in water.     

Inclusion of the Antidepressant Paroxetine in β-cyclodextrin

The X-ray structure and thermal stability of a -cyclodextrin inclusion complex of the antidepressant paroxetine [(3S-trans)-3-[(1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine], with the formula ( -cyclodextrin)₂...paroxetine...28H₂O, are reported. On heating, the crystals dehydrate in two stages and begin to decompose from approximately 270 °C. An X-ray diffraction study at 173K showed that the complex crystallizes in the monoclinic system, space group P2₁ with a = 15.2262(3), b = 31.4771(1), c = 15.6739(1) Å, = 104.320(1)° and Z = 2 formula units. Refinement on F² converged at R1 = 0.066, wR₂ = 0.182 (21478 reflections). On encapsulation within a head-to-head -cyclodextrin dimer, the paroxetine molecule adopts an unusual `hairpin' conformation, stabilised by intramolecular ... interaction between the phenyl rings. The guest piperidine ring is located at the primary face of one host molecule of the dimer while the fluorophenyl and benzodioxole moieties respectively occupy the dimer interfacial region and the cavity of the second host molecule. Experimental and computed X-ray powder diffraction patterns for the complex are also reported. The mode of stacking of the dimeric complex units is shown to be one of at least three distinct variants which can be identified for -cyclodextrin complexes with similar unit cell dimensions and crystallizing in the same space group.