Formation Constants Of Inclusion Complexes Research Articles

Stability of the Inclusion Complexes of Dodecanoic Acid with α-Cyclodextrin, β-Cyclodextrin and 2-HP-β-Cyclodextrin

In the presented work, the stability of the formation of inclusion complexes of dodecanoic acid (lauric acid) with three cyclodextrins, α-cyclodextrin, β-cyclodextrin and 2-HP-β-cyclodextrin, was analyzed from the point of view of the size of the cavity in cyclodextrins, their molar mass and the structure of the studied fatty acid. The measurements were made in a wide temperature range of 283.15-318.15K. The conductometric method was used for these studies. The results obtained allowed us to determine the value of the theoretical limiting molar conductivity (Λm0) of the studied complexes, the values of the inclusion complex formation constants (Kf) and the values of thermodynamic functions (ΔG0, ΔH0 and ΔS0) describing the complexation process in the studied temperature range.

Enantioseparation of three constitutional isomeric 2-(methylphenyl)propanoic acids by countercurrent chromatography

2-(3-Methylphenyl)propanic acid and 2-(4-methylphenyl)propanoic acid were successfully enantioseparated by countercurrent chromatography using hydroxypropyl-β-cyclodextrin (HP-β-CD) as a chiral selector. 2-(2-Methylphenyl)propanoic acid was also studied to compare the enantioseparation ability of three isomeric 2-(methylphenyl)propanoic acids. Totally 20 mg of 2-(3-methylphenyl)propanic acid and 20mg of 2-(4-methylphenyl)propanic acid were enantioseparated individually by countercurrent chromatography. Recovery for the (±)-2-(3-methylphenyl)propanic acid enantiomer was in the range of 85%-90% with 98.0%-98.8% purity and recovery for the (±)-2-(4-methylphenyl)propanic acid enantiomer was in the range of 80%-83% with 97.0%-98.0% purity. The enantioseparation factor in countercurrent chromatography for 2-(4-methylphenyl)propanic acid and 2-(3-methylphenyl)propanic acid were 1.31 and 1.26, and the peak resolution in HPLC reached 2.2 and 1.4. However, no enantioseparation could be found for 2-(2-methylphenyl)propanic acid. In addition, the inclusion complexes were investigated by UV spectrophotometer. The inclusion formation constant of inclusion complex between 2-(4-methylphenyl)propanic acid, 2-(3-methylphenyl)propanic acid, 2-(2-methylphenyl)propanic acid and HP-β-CD were determined as 121.73 mol/L, 78.12 mol/L and 53.18 mol/L, respectively. The present results showed that enantiorecognition was greatly affected by substituted positions of methyl group on the benzene ring. Combined with our previous results, the steric hindrance had a significant effect on inclusion interaction between HP-β-CD and racemic 2-(substitutedphenyl)propanoic acids. No enantiorecognition could be achieved for 2-(substitutedphenyl)propanoic acids with ortho-substituent group on benzene, while the influence of meta- and para- group on enantiorecognition varies with different substituent groups on benzene ring.

New insights on the spectrophotometric determination of melatonin pKa values and melatonin-βCD inclusion complex formation constant

Using UV–Vis spectrophotometry a stability study of melatonin at different pH values was done in aqueous media, finding that at acidic pH melatonin is unstable when interacting with the environment, however it becomes stable protecting it from light and oxygen. From the UV–Vis spectra and SQUAD software, melatonin pKa values, in a completely protected aqueous medium, were estimated as 5.777±0.011 and 10.201±0.024. Using the same techniques, the melatonin and β-cyclodextrin inclusion complex formation constants were assessed at pH3, 7 and 11.5, giving the values of log β=(3.07±0.06), (2.94±0.01) and (3.07±0.06) M−1, respectively. From the global acidity formation constants and the complexes' formation constants, the molar fractions were determined for each species of MT and MT−βCD, to build the molar fraction–[βCD]–pH 3D diagram and the molar fraction-pH 2D diagrams, where it was possible to observe the predominance of the MT species with and without βCD. A voltammetric study at pH3, allowed obtaining a value of log β=(3.15±0.01) M−1, which corroborates that obtained through UV–Vis spectrophotometry, supporting strongly the rationale behind using simple, straightforward techniques.

PREPARATION AND SPECTRA PROPERTIES OF INCLUSION COMPLEXES OF VITAMIN E WITH β-CYCLODEXTRIN

ABSTRACT Preparation of the inclusion complex of vitamin E (VE) with β-cyclodextrin (β-CD) was carried out by three kinds of methods including solution, ultrasonic and microwave radiation. The influence of temperature, inclusion time and molar ratio of VE to β-CD on the inclusion rate was investigated. The spectrum properties of inclusion complex were characterized by the ultraviolet, Fourier transformation-infrared spectroscopy and fluorescence spectrums. The experiment results confirmed the existence of 1:1 inclusion complex of VE with β-CD. The formation constant of inclusion complex was also determined by fluorescence spectrometry. It can be seen that fluorescence signals are significantly increased and enhanced with increasing concentration of β-CD. PRACTICAL APPLICATIONS Vitamin E (VE) is a strong and effective free radical scavenger; its main function is to protect the body cells and biological macromolecules from the radical attacks, and it has a good effect in the anti-aging, the prevention and treatment of cardiovascular diseases and anti-tumor. But its effect is damaged when it is exposed to oxygen, ultraviolet, alkaline, iron salt and lead salt. In pharmaceutical industries, the inclusion process of pharmaceutical molecules with cyclodextrins led to important modifications of pharmaceutical properties of guest molecules. The inclusion complex of VE with β-cyclodextrin extends to enhance solubility, chemical stability and bioavailability of poorly soluble drugs, to reduce toxicity and to control the rate of release. Therefore, it is essential to comprehensively understand the effects of inclusion about pharmaceutical molecules.

Separation and migration behavior of positional and structural naphthalenesulfonate isomers by cyclodextrin-mediated capillary electrophoresis

The effects of the type of buffer system, buffer pH, the polarity of electrode, and both the type and the concentration of cyclodextrins (CDs) on the separation and migration behavior of seven positional and structural naphthalenesulfonate isomers in CD-mediated capillary electrophoresis were systematically investigated. The most effective separation conditions were to use 20 mM phosphate buffer with β-CD at pH 3.0, while the polarity of the electrodes were reversed across the capillary. Under such conditions, these isomers can be separated in 10 min. The results also indicate that the interactions of naphthalenesulfonate derivatives with CDs are strongly affected by the position of the substituent(s) on the aromatic ring. The inclusion complex formation constants of these compounds were evaluated to improve our understanding of the interaction between the naphthalenesulfonate derivatives and CDs. Moreover, the formation constants of naphthalene-2-sulfonate to β-CD agreed closely with the data in the literature obtained by a spectrophotometric method and by CE methods in various pH buffers.

Analytical Improvement in Measuring Formation Constants of Inclusion Complexes between β-Cyclodextrin and Phenolic Compounds

Inclusion complex formation betweensixteen para-substituted phenols andβ-cyclodextrin have been investigated in orderto establish Quantitative Structure AffinityRelationships. An analytical methodology is proposed,in order to obtain reliable evaluation of bindingaffinities. Potentiometry and circular dichroism havebeen applied to define experimental conditions and toconfirm postulated equilibriums. In addition, the useof algorithmic treatments and concentrationoptimisation to determine formation constants leads tocoherent values between 1H NMR, direct UVSpectroscopy and the spectral displacement method. Theresults emphasise the contribution of van der Waalsinteractions, provided that no significant differencein the dipole of the molecule arises from thepara-substituent.

Determination of formation constants of cyclodextrin inclusion complexes using affinity capillary electrophoresis

The present study describes the application of the method of affinity capillary electrophoresis (ACE) to investigate interactions between five types of cyclodextrins (CD) and model drugs. While the drugs were injected as sample solution, the effect of different CD types and concentrations in the run buffer was studied. Mathematical models were developed to evaluate the inclusion complex formation constants and the mobilities of the complexes. Further stoichiometric constants were determined, and different models for interpretation of these results were suggested. It was evident that size and hydrophobicity of drugs have a stronger influence on the formation of inclusion complexes than the charge of drugs. β-CD and its derivatives show the strongest interactions with drugs. The handling of the described technique as well as the mathematical description are very simple. The evaluation of the different mathematical models yielded similar results. The use of a nonlinear equation enables an improved fit to experimental data. The present results demonstrate that ACE is valuable as a rapid screening method to characterize inclusion complexes between drugs and CDs. ©1999 John Wiley & Sons, Inc. J Micro Sep 11: 215–222, 1999

The equilibrium constant of β-cyclodextrin–phenolphtalein complex; influence of temperature and tetrahydrofuran addition

The temperature influence on creation of a supramolecular complex in which β-cyclodextrin (β-CD) is the host molecule and phenolphtalein (PP) is the guest has been studied in aqueous solution by UV-visible absorption spectroscopy. The decrease of temperature of β-cyclodextrin-phenolphtalein system resulted in a decrease in absorbance of the UV-vis spectrum. Under favourable conditions (0.1 mM β-CD, 30 μM PP) the termochromic effect is very significant (≅0.1 U of absorbance/10°C). The formation constant of inclusion complex was determined at various temperatures (from 10 to 70°C) using Scott’s equation. The association constants (K11) for the binding in 0.02 M sodium carbonate (pH 10.5) at 10 and 70°C are 7.44 and 0.26×104 M−1, respectively. The stoichiometric ratio of investigated complex was found to be 1:1 on wide range of β-cyclodextrin:phenolphtalein concentration ratio (from 0.8:1 to 427:1). Additionally, strong interaction between cyclodextrin and tetrahydrofuran (THF) was observed and the inhibitory effect of tetrahydrofurane on the association of β-CD–PP complex was studied. From linear Van’t Hoff plots thermodynamic parameters such as: the change of enthalpy (ΔH°) and change of entropy (ΔS°) were estimated and interpreted.

Capillary electrophoretic separation of mono- and dimaltosyl-β-cyclodextrins and determination of the stability constants of their benzoate complexes

Capillary zone electrophoresis method has been developed for the separation (and determination) of monoand dimaltosyl-β-cyclodextrins using indirect UV absorbance detection. The separation is based on inclusion complex formation with benzoate ion which is used as background electrolyte and absorbance provider simultaneously. Good resolution of cyclodextrin mixtures can be achieved optimizing the pH and the benzoic acid concentration in the background electrolyte. Capillary zone electrophoresis method has also been developed for the determination of formation constants of inclusion complexes.

Inclusion complex formation constants of α-, β-, γ-, δ-, ε-, ζ-, η- and θ-cyclodextrins determined with capillary zone electrophoresis

In contrast to the well known small cyclodextrins (CD), cyclomaltohexaose ( α-CD), cyclomaltoheptaose ( β-CD) and cyclomaltooctaose ( γ-CD), very limited information is available on larger CD and their inclusion complex forming properties. Using capillary electrophoresis, the binding constants of inclusion complexes formed with cyclomaltononaose ( δ-CD), cyclomaltodecaose ( ε-CD), cyclomaltoundecaose ( ζ-CD), cyclomaltododecaose ( η-CD) and cyclomaltotridecaose ( θ-CD) and various anions were determined and compared to the corresponding binding constants of α-, β- and γ-CD. All of the large CD were capable to form inclusion complexes. Dependent on the type of guest molecules, δ- and ε-CD were the weakest complex formers. The complex forming ability of ε, ζ-, η-, and θ-CD increased with increasing size of the ring structure and θ-CD displayed inclusion complex formation constants comparable to γ-CD.

Capillary electrophoresis of glutamate and aspartate in rat brain dialysate Improvements in detection and analysis time using cyclodextrins

Addition of cyclodextrins (CDs) to the electrolyte buffer in the capillary zone electrophoresis (CZE) separation of derivatized amino acids was evaluated in terms of fluorescence signal enhancement, resolution, and migration time effects. Maximum fluorescence signal enhancement was observed with separation buffers containing 4M β-cyclodextrin or 10 m M hydroxypropyl β-cyclodextrin. Resolution values decreased as the CD concentrations increased. Migration times were dependent on CD concentration. Inclusion complex formation constants calculated using changes in migration time showed slight agreement with those calculated by the steady-state fluorescence enhancement technique. Analysis of 20 μl of rat brain microdialysate by CZE using 4 m M β-cyclodextrin in borate buffer resulted in baseline resolution of glutamate and aspartate in 3.6 min. The results of this work indicate that, when used as separation buffer additives, cyclodextrins are capable of increasing the fluorescence signal and decreasing the migration times of NDA-derivatized acidic amino acids.

Formation constants of polynuclear aromatic compounds and β-cyclodextrin inclusion complexes in β-cyclodextrin modified mobile phase high performance liquid chromatography system

The effects of molecular size and shape upon the formation of inclusion complexes of β-cyclodextrin (β-CD) and polynuclear aromatic compounds in β-CD modified mobile phase high performance liquid chromatography (HPLC) system were studied. A correlation was established between the molecular size and shape of the probe compounds and the formation constants of the inclusion complexes. The formation constants were then used to support the elucidation of inclusion complexes formation based on the structural properties.

Binding forces contributing to reversed-phase liquid chromatographic retention on a β-cyclodextrin bonded phase

Reversed-phase liquid chromatographic (RPLC) capacity factors for a number of organic solutes on a β-cyclodextrin (β-CD) bonded phase column in pure water mobile phase ( k w ) were compared with formation constants of inclusion complexes ( k′ f) between β-CD and the solutes based on the linear solvation energy relationship (LSER) in order to understand the types and relative strengths of various intermolecular forces between CD and the guest solute affecting the stability of inclusion complexes and hence retention in RPLC. A close fit of capacity factors ( k′ w) with complexation constants indicated that inclusion complexation is the major driving force in retention on the β-CD-bonded phase in RPLC. Comparison of LSERs for K f and k′ w showed that an increasing guest molecular size stabilizes the complex by virtue of increasing dispersive interactions between the hydrophobic interior of CD cavity and the guest and hence increases the RPLC retention, and that increasing guest dipolarity and hydrogen bond (HB) acceptor basicity lead to a decrease in the stability of the complex due to the stronger dipolar and HB interactions with water, and hence decrease the retention.

Capillary electrophoretic analysis of cyclodextrins and determination of formation constants for inclusion complexes.

Capillary zone electrophoresis (CZE) methods with indirect absorbance detection for analyzing mixtures of alpha-, beta-, and gamma-cyclodextrins (CDs) and their derivatives have been developed. Benzylamine, salicylic, sorbic, or 1-naphthylacetic acid (NAA) was utilized as background electrolyte (BGE) and absorbance provider. Separation of alpha-, beta-, and gamma-CD could be achieved in less than 18 min when the CZE was run in 2 mM NAA or 5 mM sorbate solution (pH 12.2) and detected by indirect absorbance at 222 or 254 nm, respectively. Mixtures of alpha- and beta-CDs, and dimethyl- and trimethyl-derivatives of beta-CD could also be analyzed by CZE, using 50 mM salicylic acid or benzylamine solution (pH 6.0) as BGE with indirect absorbance detection at 230 and 210 nm, respectively. CZE methods for determining the inclusion complex formation constants of various CDs for salicylic acid or benzylamine with either direct or indirect absorbance detection have also been developed. The formation constants of salicylate are in the range from ca. 8 +/- 0.3 mole-1 for the complex with alpha-CD to ca. 99 +/- 2 molarity-1 for the complex with methyl-beta-CD. The detection limits (determined at a signal-to-noise ratio of 3) for the NAA and the salicylate system are ca. 0.1 mM and 1 mM, respectively.

Application of Gel Chromatography to Determining Formation Constants of Inclusion Compounds of Cyclodextrins

Abstract The gel filtration technique (Hummel and Dreyer method) was applied to determining formation constants of inclusion complexes of α- and β-cyclodextrins. As guest substances, p-nitrophenolate, p-nitrophenol, benzoate, and benzoic acid were used. Formation constants were determined at room temperature (25–30 °C) using Sephadex G-10 gel in aqueous buffered solutions of a constant ionic strength of 0.5 with NaCl or with phosphate buffer, and the results were compared with literature values. The method is applicable to such guest substances as exhibit strong adsorption onto the gel matrix.

Inclusion complexes of .BETA.-cyclodextrin with tranquilizing drugs phenothiazines in aqueous solution.

The interaction of tranquilizing drugs phenothiazines with β-cyclodextrin in aqueous solution was studied by circular dichroism, ultraviolet (UV) absorption, and proton magnetic resonance spectroscopies. The induced circular dichroism bands and UV absorption changes were quantitatively investigated and stoichiometric ratio, which was found to be 1 : 1, and formation constants of inclusion complexes were obtained. In β-cyclodextrin-drug system, protons located in a cavity of β-cyclodextrin were found to be subjected to anisotropic shielding, while protons of phenyl and N-substituted groups in the drug shifted to low field, in which all peaks caused remarkable broadening. Formation constants were correlated well with partition coefficient of drug and also with the magnitude of proton magnetic resonance spectral broadening. These spectral changes strongly suggested that aromatic portion of drug was included into hydrophobic cavity of β-cyclodextrin, while N-substituents of drug interacted with the outside groups of β-cyclodextrin cavity.