Thermodynamics of inclusion complexes between cyclodextrins and isoniazid

Complex formation of α- and β-cyclodextrins with isoniazid, a antituberculous pharmaceutical, is studied using such methods as calorimetry and ¹H NMR at 298.15 K. On the basis of the obtained experimental data, it is shown that α- and β-cyclodextrins form 1 : 1 inclusion complexes with isoniazid, which are characterized by low stability in aqueous solution. Along with this, deeper penetration of isoniazid into the cavity of β-cyclodextrin, accompanied by more intensive dehydration of the reagents, is observed. The results are interpreted in terms of influence of structure of reagents and their state in solution on the binding mode, driving forces, and thermodynamic parameters of the complex formation.     

Phosphorescence of lyophilized complexes between cyclodextrins andβ-arylpropiophenones

-Arylpropiophenones do not phosphoresce in homogeneous solution as a result of excited state quenching by the -aryl group. In the presence of cyclodextrins the parent substrate, -phenylpropiophenone, shows readily detectable phosphorescence. The complexes show strong phosphorescence after lyophilization to dryness. The phosphorescence intensity of ring-substituted derivatives is strongly dependent upon molecular size and cavity dimensions, suggesting that the -arylpropiophenones can be used to probe these properties.Issued as NRCC-23907     

Evidence of different stoichiometries for the limiting carbonate complexes across the lanthanide(III) series: a capillary electrophoresis-mass spectrometry study

The electrophoretic mobilities (mu ep,Ln) of twelve lanthanides (not Ce, Pr and Yb) were measured by CE-ICP-MS in 0.15 and 0.5 mol L(-1) Alk2 CO3 aqueous solutions for Alk+ = Li+, Na+, K+ and Cs+. In 0.5 mol L(-1) solutions, two different mu ep,Ln values were found for the light (La to Nd) and the heavy (Dy to Tm) lanthanides, which suggests two different stoichiometries for the carbonate limiting complexes. These results are consistent with a solubility study that attests the Ln(CO3)3(3-) and Ln(CO3)4(5-) stoichiometries for the heavy (small) and the light (big) lanthanides, respectively. The Alk+ counterions influence the mu ep,Ln Alk2 CO3 values, but not the overall shape of the mu ep,Ln Alk2 CO3 plots as a function of the lanthanide atomic numbers: the counterions do not modify the stoichiometries of the inner sphere complexes. The influence of the Alk+ counterions decreases in the Li+ > Na+ > K+ > Cs+ series. The K3,Ln stepwise formation constants of the Ln(CO3)3(3-) complexes slightly increase with the atomic numbers of the lanthanides while K4,Ln, the stepwise formation constants of Ln(CO3)4(5-) complexes, slightly decrease from La to Tb, and is no longer measurable for heavier lanthanides.     

Cryptophane-xenon complexes in organic solvents observed through NMR spectroscopy

The interaction of xenon with cryptophane derivatives is analyzed by NMR by using either thermal or hyperpolarized noble gas. Twelve hosts differing by their stereochemistry, cavity size, and the nature and the number of the substituents on the aromatic rings have been included in the study, in the aim of extracting some clues for the optimization of (129)Xe-NMR based biosensors derived from these cage molecules. Four important properties have been examined: xenon-host binding constant, in-out exchange rate of the noble gas, chemical shift, and relaxation of caged xenon. This work aims at understanding the main characteristics of the host-guest interaction in order to choose the best candidate for the biosensing approach. Moreover, rationalizing xenon chemical shift as a function of structural parameters would also help for setting up multiplexing applications. Xenon exhibits the highest affinity for the smallest cryptophane, namely cryptophane-111, and a long relaxation time inside it, convenient for conservation of its hyperpolarization. However, very slow in-out xenon exchange could represent a limitation for its future applicability for the biosensing approach, because the replenishment of the cage in laser-polarized xenon, enabling a further gain in sensitivity, cannot be fully exploited.     

The utility of cyclodextrins in lipase-catalyzed transesterification in organic solvents: enhanced reaction rate and enantioselectivity

The use of enzymes as valuable catalysts in organic solvents has been well documented. However, some of their features limit their application in organic synthesis, especially the frequently lower enzyme activity under nonaqueous conditions, which constitutes a major drawback in the application of enzymes in organic solvents. In addition, many enzymatic reactions are subject to substrate or product inhibition, leading to a decrease in the reaction rate and enantioselectivity. To overcome these drawbacks and to make enzymes more appealing to organic chemists, we demonstrate the use of cyclodextrins as regulators for the Pseudomonas cepacia lipase (PSL) and macrocyclic additives to enhance the reaction rate and enantioselectivity E in lipase-catalyzed enantioselective transesterification of 1-(2-furyl)ethanol in organic solvents. Both reaction rate and enantioselectivity were significantly enhanced by several orders of magnitude when using co-lyophilized lipase in the presence of cyclodextrins. The effect of cyclodextrin derivatives as well as solvents on the improvement of the reaction parameters has been studied. The observed enhancement was tentatively interpreted in terms of their ability to give a certain flexibility to the enzyme and to form a host-guest complex, thus avoiding product inhibition and leading to enhancement of the reaction rate and enantioselectivity. The effect of cyclodextrin additives on the enzyme morphology has been studied using scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) of the co-lyophilized lipase with cyclodextrins. The ability of cyclodextrins to form a host-guest complex to avoid product inhibition, which leads to the observed enhancement, has been proved by NOESY, COSY, 13C and 1H NMR.     

Inclusion complexes between cyclic siloxanes and cyclodextrins: synthesis and characterization

Molecular inclusion complexes between cyclodextrins and cyclic siloxanes were prepared and characterized via a combination of liquid and solid state NMR, FT-IR, TGA, powder X-ray diffraction, SEM–EDS and elemental analyses. The crystalline complexes adopted the channel-type conformation. Depending from the size of both the cyclic sugar cavity and the silicon guest, various yields (between 0 and 41%) and host–guest molar ratios (between 1:1 and 4:1) were obtained. α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) were observed to form crystalline inclusion complexes only with D₃ (cyclic dimethyltrisiloxane) due to steric effects, whereas the larger γ-cyclodextrin (γ-CD) formed inclusion complexes both with D₃, D₄ (cyclic dimethyltetrasiloxane) and D₅ (cyclic dimethylpentasiloxane). This study is believed to be the first step towards the selective removal of cyclic siloxanes impurities from commercial PDMS preparations.     

Relationships between the stability,circular dichroism spectrum and type of substitution in inclusion complexes formed between phenophthalein and different cyclodextrins

The perturbation of the three-site interaction of phenolphthalein on complexation with different cyclodextrins (CDs) has been investigated as a function of the type and degree of substitution of the CD. The UV visible spectra are practically identical, while the circular dichroism spectra change dramatically both in intensities and signs. Parallel to this, the stability constants are influenced not only by the size of the cavity but also by the substitution of its rims, particularly by that of the primary hydroxyls. The two phenomena can be related to allow conclusions concerning the mode of inclusion.     

The solubilities of denatured proteins in different organic solvents

The solubilities of heat-denatured and reduced, S-carboxymethylated proteins have been investigated in various organic solvents. Polar, protic solvents (formic acid, trifluoroacetic acid, 3-mercaptopropionic acid) were found to be good solvents for the denatured proteins (20-40 mg ml-1), and the solubilities of the reduced, S-carboxymethylated proteins were generally higher than those of the heat-denatured forms. Most other organic solvents were less effective in solubilizing the denatured proteins. Apolar solvents did not solubilise denatured proteins, but low solubilizing powers were observed for polar, aprotic solvents. Heat-denaturation was observed to result in the formation of large intermolecular aggregates, which, for ovalbumin and lysozyme, were formed by intermolecular S-S bonds, but for bovine serum albumin involved intermolecular isopeptide bonds.     

Investigation of the effects of cyclodextrins and organic solvents on the separation of cationic surfactants in capillary electrophoresis

The use of alpha- and beta-cyclodextrin (CD) to understand and to improve the separation of a series of cationic surfactants, homologues of alkylbenzyldimethyl ammonium compounds (ABDACs) with an alkyl chain of varying length (C10-C18), in capillary electrophoresis (CE) is reported for the first time. Similar to the effects of organic solvents, the presence of alpha- or beta-CD in the running buffer was found to reduce peak tailing/loss for the longer-chain ABDACs. Based on fluorescence measurements, it was found that formation of host-guest complexes occurred between alpha- or beta-CD and various ABDACs, with the likelihood that the hydrophobic alkyl chain including into the CD cavity and the positively charged ammonium group remaining outside the cavity. The effects of alpha- or beta-CD can be interpreted in terms of a shift away from the formation of (1) micelles in the buffer system and (2) surfactant aggregates at the fused-silica capillary walls, as a result of the formation of inclusion complexes between alpha- or beta-CD and ABDACs.     

Supramolecular complexes of spin-labelled cyclodextrins

EPR spectra of cyclodextrins labelled with TEMPO derivatives (SL-CDs) are sensitive to complexation with large guest molecules. We used SL-CDs to explore the behaviour of concentrated PEG/PPG solutions. The relationship between rotational correlation times and solvent viscosity showed significant deviations from the Debye-Stokes-Einstein equation, probably due to self-aggregation of alkylene glycols in concentrated solutions. The data fit the fractional Debye-Stokes-Einstein equation well. We have also studied complexation of SL-CDs with adamantane-functionalised DAB dendrimers. The strength of binding increases with dendrimer generation; formation of supramolecular aggregates at high concentrations was observed with the generation 3 dendrimer.     

NMR spectroscopic investigation of inclusion complexes between cyclodextrins and the neurotoxin tetramethylenedisulfotetramine

The binding stoichiometry, strength and structure of inclusion complexes formed between the neurotoxin tetramethylenedisulfotetramine (TETS) and both native and modified cyclodextrins (CyDs) were investigated using nuclear magnetic resonance (NMR) spectroscopy. Of all six examined cases, native β‐cyclodextrin (β‐CyD) and its chemically modified counterpart heptakis‐(2,3,6‐tris‐(2‐hydroxypropyl))‐β‐cyclodextrin (2HP‐β‐CyD) were found to associate most strongly with TETS as reflected in the magnitude of their binding constants (K = 537 ± 26 M^?1 for β‐CyD and K = 514 ± 49 M^?1 for 2HP‐β‐CyD). Two‐dimensional rotating‐frame Overhauser effect spectroscopy NMR experiments confirm close proximity of the TETS molecule to both β‐CyD and 2HP‐β‐CyD as intermolecular, through‐space interactions between the H3 and H5 protons located in the interior of the CyD cavity and the methylene protons of TETS were identified. Copyright © 2012 John Wiley & Sons, Ltd.     

Inclusion complexes of amlodipine besylate and cyclodextrins

In this paper the procedure for the preparation of inclusion complexes of amlodipine besylate with β-cyclodextrin (β-CD) and 2-hydrohypropyl-β-cyclodextrin (HPβ-CD) and their structural characterization was described. Molecular inclusion complexes of amlodipine besylate are prepared by the coprecipitation method and characterised by the application of spectroscopic methods FTIR, ¹H-NMR and XRD. The photosensitivity of amlodipine besylate in the inclusion complexes was also determined with respect to uncomplexed agent. DSC curves indicate the loss of the clear peak due to melting of amlodipine besylate at about 200°C, while on XR diffractograms certain reflections are lost belonging to amlodipine besylate in complexes. This indicates its inclusion in the vacancies of the host. The inclusion of amlodipine besylate with cyclodextrins increases the stability, i.e. decreases the photosensitivity of amlodipine besylate.      

Solubility and limiting activity coefficient of simvastatin in different organic solvents

Equilibrium mole fraction solubility of Zocor^® (simvastatin) a pharmaceutically important compound, was measured between 279 and 315 K, in fifteen different industrial-relevant organic solvents including: methyl acetate, ethyl acetate, propyl acetate, iso-propyl acetate, butyl acetate, iso-butyl acetate, sec-butyl acetate, tert-butyl acetate, and ethanol, propanol, 1-butanol, 2-butanol, 1-pentanol, 1-hexanol, and 1-octanol. Fusion enthalpy, Δ_fusH, melting point temperature, T_m, were measured to be 32,169 J/mol, 412.6 K, respectively; and the difference in the molar heat capacity (at constant pressure) of the liquid, and solid form of simvastatin, ΔC_P, was approximated (by extrapolation) to be 230 J/mol K. Dissolution of simvastatin was found to be endothermic, and entropically favorable. The activity coefficient at infinite dilution of simvastatin in each solvent was calculated from the experimental data, then fitted to Gibbs–Helmholtz equation to estimate the limiting partial molar excess enthalpies, , and the limiting partial molar excess entropies, . The data was also fitted to the non-random-two-liquid (NRTL) activity coefficient equation to generate the model interaction parameters for dissolution of simvastatin in the organic solvents studied here.     

Transfer activity coefficients of crown ethers and their complexes with univalent metal ions between pairs of polar organic solvents

From a comparison of transfer activity coefficients, [(LM⁺)]_PC,2 between propylene carbonate and solvent S₂ of alkali or silver ions complexed with dibenzo-substituted crown ethers (L=DB-18-cr-6, DB-21-cr-7, DB-24-cr-8, DB-30-cr-10) it can be concluded that in the complex LM⁺ both L and M⁺ are solvated, particularly in solvents of high donicity, e.g., N,N-dimethylformamide. From the abnormally low ionic mobility of DB-30-cr-10K⁺ in acetonitrile and the high value of the association constant of the ion pair DB-30-cr-10KBr it is concluded that the outer solvent shell is stripped upon formation of the ligand separated ion pair. A linear relation is found between [log (LM⁺)]_PC,2 and [log(M⁺)]_PC,2 only when L is 18-cr-6, B-18-cr-6, or DB-18-cr-6. Deviation from the linearity of complexes of the larger dibenzo crown ethers is attributed to the flexibility of L. It is shown that solution of 18-cr-6, DB-18-cr-6 and DB-30-cr-10 is enthalpy assisted to a greater extent in acetonitrile than in methanol, while the entropy of solution is more favorable in the latter.     

Distribution of carboxylic acids between water and nonpolar organic solvents

Equations which describe the distribution of carboxylic acids between water and nonpolar organic solvents, and which make allowance for their dimerization in the organic solvent, their association with water molecules, and the nonideal nature of the organic phase, have been examined. It has been shown that it is necessary to study the distribution of the carboxylic acid and water between the phases in order to determine the constants for the distribution, hydration, and dimerization of the carboxylic acids.     

Determination of metal-ligand stoichiometries for inorganic complexes using total reflection X-ray fluorescence

The methods usually used to determine the ratio metal-ligand in inorganic complexes require a set of solutions with different concentrations for both the ligand and metal. We propose a new method using the total reflection X-ray fluorescence technique, in which the ratio between metal and ligand is determined precisely, easily, and quickly. Experimental results provide evidence that for different chemical complexes, the ligand-metal ratio determined by this technique deviates at most from stoichiometric values by 6%. The technique is restricted usually to elements with Z above 14, and its detection limit is on the order of 10(-8) g/g.     

Solubility of naproxen in several organic solvents at different temperatures

By using the van’t Hoff and Gibbs equations the thermodynamic functions Gibbs free energy, enthalpy, and entropy of solution, were evaluated from solubility data of naproxen (NAP) determined at several temperatures in octanol, isopropyl myristate, chloroform, and cyclohexane, as pure solvents. The water-saturated organic solvents also were studied except cyclohexane. The excess free energy and the activity coefficients of the solutes, and the mixing and solvation thermodynamic quantities were also determined. The NAP solubilities were higher in chloroform and octanol with respect to those obtained in cyclohexane. In addition, by using literature values for NAP aqueous solubility, the thermodynamic functions relative to transfer of this drug from water to organic solvents were also estimated.     

Self-assembly of the pre-formed inclusion complexes between cyclodextrins and alkanethiols on gold electrodes

A new kind of self-assembled monolayer (SAM) formed in aqueous solution through the pre-formed inclusion complexes (abbreviated CD · C_n) between α, β-cyclodextrins (CDs) and alkanethiols (CH₃(CH₂)_n−1)SH, n = 10, 14 and 18) was prepared successfully on gold electrodes. High-resolution ¹H NMR was used to confirm the formation of CD · C_n. X-ray photoelectron spectroscopy, cyclic voltammetry and chronoamperometry were used to characterize the resulting SAMs (denoted as M_CD·Cn). It was found that M_CD·Cn were more stable against repeated potential cycling in 0.5 M H₂SO₄ than SAMs of CH₃(CH₂)_n−1SH (denoted as M_Cn), with a relative sequence of M_β−CD·Cn > M_α−CD·Cn > M_Cn. In addition, an order of blocking the electron transfer between gold electrodes and redox couples (both Fe(CN)³₆ and Ru(NH₃)³⁴₆) in solution, M_CD·C10 > M_CD·C14 > M_CD·C18, was observed. A plausible explanation is provided to elucidate some of the observations.     

A radiotracer technique for determining the solubilities of thallium crown ether complexes in organic solvents

A radiotracer method to measure the solubility of thallium crown ether complexes is reported. Tl-204 is used as the radiotracer. The method is capable of a precision of 1% or better. The solubilities of 18-crown-6-bis-/thallium-o-nitrophenoxide/ in acetonitrile, benzene, chloroform and DMF were measured.     

混配铂(Ⅱ)配合物堆积异构平衡的溶剂效应

在三元混配配合物中配体与配体之间的分子内芳环堆积是配体分子间的一种特殊作用形式 ,并且在溶液中存在着堆积异构平衡。这种由芳环堆积所产生的异构平衡也同样存在于生物体系内 ,并有着重要的生理效应[1 ,2 ] 。因而有关三元混配配合物分子内芳环堆积异构平衡的研究十分活跃[3～ 5] 。本文选定了羧酸系列配体 (ＣＡ)和另一配体 1 ,1 0 邻菲绕啉 (Ｐｈｅｎ)与铂 (Ⅱ)形成的三元混配配合物作为体系 ,系统研究了溶剂极性对三元混配配合物分子内芳环堆积异构平衡的影响。1　实验部分1 1　试剂和溶液标定氯铂酸钾 [Ｋ2 (ＰｔＣｌ4) ]、硝酸 (…