Stability Constants Of Inclusion Complexes Research Articles

In Vitro Cytotoxicity and In Vivo Antitumor Efficacy of Tetrazolato-Bridged Dinuclear Platinum(II) Complexes with a Bulky Substituent at Tetrazole C5

Tetrazolato-bridged dinuclear platinum(II) complexes ([{cis-Pt(NH3)2}2(μ-OH)(μ-5-R-tetrazolato-N2,N3)]2+; tetrazolato-bridged complexes) are a promising source of next-generation platinum-based drugs. β-Cyclodextrin (β-CD) forms inclusion complexes with bulky organic compounds or substituents, changing their polarity and molecular dimensions. Here, we determined by 1H-NMR spectroscopy, the stability constants for inclusion complexes formed between β-CD and tetrazolato-bridged complexes with a bulky, lipophilic substituent at tetrazole C5 (complexes 1–3, phenyl, n-nonyl, and adamantyl substitution, respectively). We then determined the in vitro cytotoxicity and in vivo antitumor efficacy of complexes 1–3 against the Colon-26 colorectal cancer cell line in the absence or presence of equimolar β-CD. Compared with the platinum-based anticancer drug oxaliplatin (1R,2R-diaminocyclohexane)oxalatoplatinum(II)), complex 2 had similar cytotoxicity, complex 3 was moderately cytotoxic, and complex 1 was the least cytotoxic. The cytotoxicity of the complexes decreased in the presence of β-CD. When we examined the in vivo antitumor efficacy of complexes 1–3 (10 mg/kg) against homografted Colon-26 colorectal tumors in male BALB/c mice, they showed a relatively low tumor growth inhibition compared with oxaliplatin. However, in the presence of β-CD, complex 3 had higher in vivo antitumor efficacy than oxaliplatin, suggesting a new direction for future research into tetrazolato-bridged complexes with high in vivo antitumor activity.

Retention of Cyclodextrins under the Conditions of Reversed-Phase Chromatography and Determining the Stability Constants of Inclusion Complexes of Antocyanins with β-Cyclodextrein

The chromatographic behavior of α, β, and γ-cyclodextrins on three types of reversed-phase chromatography of stationary phases—С4, С8, and С18—is investigated. Patterns of sorption are determined experimentally, and modeling is used to determine the nature of interaction between cyclodextrins and grafted phases. Based on the obtained results and considering experiments on the formation of a complex of β-cyclodextrin and n-hexane, it is suggested that the probability of modifying surfaces of the C4 phase with cyclodextrins in aqueous–acetonitrile mobile phases with low contents (from 5 vol %) of organic modifier is low, and the C18 phase could be used without surface modification of the sorbent when the acetonitrile content is above 10 vol %. To corroborate these conclusions, the constants of complex formation of β-cyclodextrin with some anthocyanins are determined by adding β-cyclodextrin to the mobile phase under the conditions of chromatography on the C4 phase; the same is impossible using the C18 phase.

Preparation, physicochemical characterization and release behavior of the inclusion complex of trans-anethole and β-cyclodextrin

Trans-anethole (AT) has a variety of antimicrobial properties and is widely used as food functional ingredient. However, the applications of AT are limited due to its low water solubility, strong odor and low physicochemical stability. Therefore, the aim of this work was to encapsulate AT with β-cyclodextrin (β-CD) for obtaining inclusion complex by co-precipitation method. The measurements effectively confirmed the formation of inclusion complex between AT and β-CD. The results showed that the inclusion complex presented new solid crystalline phases and was more thermally stable than the physical mixture and β-CD. The phase solubility study showed that the aqueous solubility of AT was increased by being included in β-CD. The calculated stability constant of inclusion complex was 1195M−1, indicating the strong interaction between AT and β-CD. Furthermore, the release study suggested that β-CD provided the protection for AT against evaporation. The release behavior of AT from the inclusion complex was controlled.

Determination of stability constants of inclusion complexes of betulin derivatives with β-cyclodextrin by capillary electrophoresis

Determination of stability constants of inclusion complexes of betulin derivatives with β-cyclodextrin by capillary electrophoresis

Preparation and characterization of inclusion complexes formed between baicalein and cyclodextrins

This study investigates the solubility of baicalein (Ba) with the addition of modified cyclodextrins using phase solubility method. The solubility of Ba in the presence of natural (α-, β-, and γ-) cyclodextrins and its derivatives, namely, hydroxypropyl-β-cyclodextrin (HP-β-CD) and (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), was higher than that of free Ba. In particular, the stability constant of inclusion complex with DM-β-CD was 13672.67lmol−1, which was the highest among the examined cyclodextrins. The inclusion complexes of Ba and DM-β-CD were prepared via freeze-drying method, which were both characterized in the solution and solid state by UV–vis spectroscopy, differential scanning calorimetry (DSC), proton nuclear magnetic resonance (1H NMR), scanning electron microscopy (SEM), and X-ray powder diffractometry (XRPD). The UV–vis, DSC, 1H NMR, SEM, and XRPD results proved the formation of inclusion complex between Ba and DM-β-CD. Furthermore, the dissolution rate and thermal stability of the inclusion complex were significantly enhanced compared with the pure drug. Therefore, using DM-β-CD can effectively improve the solubility and thermal stability of free Ba, which is a promising approach to promote its clinical application.

Investigation of the inclusion complex of β-cyclodextrin with mycophenolate mofetil

The acid–base equilibrium of mycophenolate mofetil is studied in the absence and presence of β-cyclodextrin (β-CD). The conditional acidity constants are obtained by rank annihilation factor analysis (RAFA) as a function of β-CD concentrations. Also the stability constants for inclusion complexes of β-CD with both acidic and basic forms are calculated. The conditional acidity constant decreases by increasing β-CD concentration. The calculated stability constants show that the acidic form of mycophenolate mofetil forms more stable inclusion complex (552±7M−1) than its basic anionic form (158±2M−1).

Interactions of β - and Hydroxypropyl-β-Cyclodextrin with Some Purine Alkaloids:Thermodynamic Study

The effect of native and hydroxypropylated beta-cyclodextrin on the solubility and activity of some purine alkaloids was examined. For this purpose, the solubility of purine alkaloids in pure water and in aqueous solutions of mentioned beta-cyclodextrins was determined at 298.15 K. Stability constants of inclusion complexes and their stoichiometry were obtained from solubility diagrams. Enthalpic characteristics of interactions occurring between beta-cyclodextrins and purine alkaloids in aqueous solution were calculated from the direct calorimetric measurements. It was found, that beta-cyclodextrin forms with purine alkaloids weak complexes which are stabilized only by the entropy term. Due to very low complexing affinity of both beta-cyclodextrins to studied purine alkaloids their solubilizing effect is insignificant. The influence of structure of purine alkaloids and beta-cyclodextrin on the thermodynamic parameters of interaction was discussed.

Influence of Cyclodextrin Complexation on the Vibrio fischeri Toxicity of Phenylsulfonyl Carboxylates

This paper describes the research about the β -cyclodextrin influence on Vibrio fischeri toxicity of 10 phenylsulfonyl carboxylates. It is illustrated that the formation of 1:1 cyclodextrin-solute inclusion complexes dominates the toxicity influence of phenylsulfonyl carboxylates to Vibrio fischeri and greatly weakens the toxicity level. Using the octanol-water partition coefficients lg K OW, the grouped electrotopological state (E-state) index S (> SO2) and the stability constants of inclusion complexes lg K S , three models with high squared correlation coefficients r2 adj at 0.908, 0.951 and 0.917, respectively were constructed to evaluate the β-cyclodextrin influence on Vibrio fischeri toxicity. For the type of phenylsulfonyl carboxylates, the inclusion stability constants lg K S can reliably model and predict the β-cyclodextrin influence on Vibrio fischeri toxicity (TI).

Determination of the Stability Constants of Inclusion Complexes of p-H-37-(2-carboxy-methyloxy)-calix-[6]-arene and p-sulphonato-37-(2-carboxy-methyloxy)-calix-[6]-arene with 15 Amino acids by RP-HPLC

Reversed-phase high performance liquid chromatography (Separon SGX CN, UV detection at 254~nm and water as mobile phase) was applied to thestudy of the host–guest complexation ofp-H-37-(2-carboxy-methyloxy)-calix-[6]-arene (1) and p-sulphonato-37-(2-carboxy-methyloxy)-calix-[6]-arene (2)with 15 amino acids in the mobile phase. It was established that the formation ofthe inclusion complexes results in changes in the retention times and capacity factorsof amino acids. Stability constants of the complexes were determined. The variations instability constant values may be explained in terms of the different interactions, whichmay occur between amino acids and 1 and 2.

ChemInform Abstract: A Comparative Study of the Determination of the Stability Constants of Inclusion Complexes of p‐Sulfonatocalix[4]arene with Amino Acids by RP‐HPLC and 1H NMR.

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A comparative study of the determination of the stability constants of inclusion complexes of p-sulfonatocalix[4]arene with amino acids by RP-HPLC and 1H NMR

Reversed-phase high-performance liquid chromatography (Separon SGX C 18, UV detection at 254 nm and acetonitrile–water–trifluoroacetic acid (70∶30∶0.5, v/v), and methanol–water–trifluoroacetic acid (3∶97∶0.5, v/v) as mobile phases) was applied to the study of the host–guest complexation of p-sulfonatocalix[4]arene (SC[4]A) with amino acids as guests in the mobile phase. It was established that the formation of the inclusion complexes results in changes in the retention times of the amino acids. Stability constants of the complexes were determined. The variations in stability constants may be explained in terms of the various interactions (ion-pairing, hydrophobic, aromatic–aromatic and electrostatic interactions) that may occur between a given amino acid and SC[4]A. For the amino acids aspartic acid and proline the association constants were also derived from 1H NMR experiments.

Cyclodextrin Inclusion Complexes of Two Non-Steroidal Antiinflammatory Drugs and of an Analgesic Drug

U.v .-visible spectrophotometric studies of the interactions of Naproxen, Ibuprofen and Panadol with α-cyclodextrin , β-cyclodextrin, γ-cyclodextrin and dimethyl β- cyclodextrin enable the determination of stability constants of inclusion complexes when their formation gives rise to appreciable spectral changes. The magnitudes of the stability constants are discussed in terms of the relative sizes and the chemical natures of the cyclodextrins and the included molecules.

Simple Prediction of Stability Constants for Inclusion Complexes of β-Cyclodextrin with various Drug Molecules Using β-Cyclodextrin Bonded Phases(Cyclobond I Column)

AbstractThe stability constants(Kc) for inclusion complexes of cyclodextrin with sulfonamides, sulfonylureas and p-aminobenzoic acid esters were investigated by high performance liquid chromatography (HPLC) using the cyclodextrin bonded phase. The retention time(Rt) of these drugs on a Cyclobond® I column showed a good relationship to K, values obtained by the solubility method and/or conventional HPLC method. The advantages of this method were that the K, values could be rapidly predicted by a simple procedure using a minimum quantity of the drugs.

Simple Prediction of Stability Constants for Inclusion Complexes of β-Cyclodextrin with various Drug Molecules Using β-Cyclodextrin Bonded Phases(Cyclobond® I Column)

The stability constants(Kc) for inclusion complexes of cyclodextrin with sulfonamides, sulfonylureas and p-aminobenzoic acid esters were investigated by high performance liquid chromatography (HPLC) using the cyclodextrin bonded phase. The retention time(Rt) of these drugs on a Cyclobond® I column showed a good relationship to K, values obtained by the solubility method and/or conventional HPLC method. The advantages of this method were that the K, values could be rapidly predicted by a simple procedure using a minimum quantity of the drugs.

Application of freezing point depression to drug interaction studies. I. Interaction between cyclodextrins and alcohols.

The osmotic pressure of dilute aqueous solutions of a cyclodextrin and an alcohol were measured separately and in combination by the freezing point depression method with a commercially available osmometer. The results could be classified into two categories; in one, the osmotic pressure of combined solutes was equal to the sum of the individual values obtained seprately. In the other case, such additivity was not maintained. In the latter case, it was assumed that the two substances form a complex. On the basis of this assumption, stability constants for inclusion complexes of cyclodextrin with a variety of alcohols were determined. The stability constants obtained here were in fair agreement with those obtained previously by other methods. Therefore, it was concluded that measurement of freezing point depression is a useful method for determination of the stability constants for complex formation in an aqueous solution. The advantages and disadvantages of this method are discussed.

Inclusion complexes of isomeric chloronitrobenzenes with α- and β-cyclodextrins studied by polarography: Analysis of the possibilities of the method

Inclusion complexes of isomeric chloronitrobenzenes with α- and β-cyclodextrins in 0.1 and 0.5 M phosphate buffer (pH = 7) have been studied by polarographic and voltammetric methods. The stability constants and the diffusion coefficients of the corresponding complexes have been determined. The possibilities of the polarographic method based on the determination of diffusion coefficients for the calculation of the stability constants of inclusion complexes have been discussed and checked using digital simulations.

Protective effects of cyclodextrins on drug-induced hemolysis in vitro.

beta-Cyclodextrin (beta-CyD) significantly protected the human erythrocytes from hemolysis and shape changes induced with chlorpromazine and flufenamic acid in isotonic solution. A good correlation between the stability constants of inclusion complexes (beta- greater than gamma- greater than alpha-CyD) and the inhibitory effects on drug-induced hemolysis was found. From the observations of drug uptake into erythrocytes and changes in surface tension, the protective effects of CyDs appeared to be due to the decrease in effective concentration of drug through inclusion complexation rather than the direct interaction of CyDs with erythrocyte membrane.

Determination of the stability constants for inclusion complexes of cyclodextrins with various drug molecules by high performance liquid chromatography.

Stability constant (Ke) for 1 : 1 inclusion complexes of α-and β-cyclodextrins with barbiturates, phenothiazines, sulfonylamides, and sulfonylureas were determined by high performance liquid chromatography (HPLC). The retention times of the drugs following the binding to cyclodextrins in aqueous mobile phase on ion exchange support were quantitatively treated to obtain the Ke values. The Ke values obtained by HPLC method were in fair agreement with those obtained by other methods such as solubility and spectroscopic methods. The advantages of HPLC method developed here were that Ke values could be rapidly obtained by simple procedure with minimum quantity of the drugs and reproducibility and accuracy were not less than other methods. Furthermore, this method was proved to be particularly suitable for chemically unstable compounds such as phenothiazines.