Inclusion Complex of 4-Hydroxycoumarin with Cyclodextrins and Its Characterization in Aqueous Solution

The physicochemical properties of 4-hydroxy-7-methoxy-3-phenyl-2H-chromen-2-one (4HC) and β-cyclodextrins (CDs) inclusion complexes were investigated. The phase solubility profile of 4HC with β-cyclodextrin derivatives was classified as A_L-type. Stability constants for complexes with 1:1 molar ratios were calculated from the phase solubility diagrams and indicate the following trend: DMβCD>HPβCD>βCD. The highest value of the binding constant was for 4HC-DMβCD; the binding association constant (K _a) for this complex was determined at different temperatures and the thermodynamic data indicate that 4HC-DMβCD association is mainly an entropically driven process. ¹H NMR and ROESY were carried out, revealing that 4HC is embedded in the apolar cavity of DMβCD with the 4OH group buried in the cyclodextrin cavity with the phenyl group outside, near the primary rim. These results are in agreement with ORAC_FL values; the decrease in the antioxidant activity of 4HC-DMβCD is explained by the effective protection of the hydroxyl group due to complexation.     

Inclusion Complexation of a Seleno-Organic Antioxidant, Ebselen, with Cyclodextrins in Aqueous Solution

The interaction of ebselen, 2-phenyl-1,2-benzisoselenazol-3(2H)-one, a novel neuroprotective agent, with cyclodextrins (CyDs) in aqueous solution was studied by the solubility method and spectroscopic methods. The ability of sulfobutyl ether -CyD (SBE7--CyD, average degree of substitution= 6.2) to solubilize ebselen was greater, and its stability constant (> 2000 M^-1) was significantly higher than those (< 1000 M^-1) of other CyD complexes employed. The stability constant of the complexes rose as hydrophobicity of the substituents of CyDs increased, whereas it was negligibly affected by change in ionic strength of the medium, indicating a significant contribution of hydrophobic interaction in the complexation. SBE7--CyD gave positive and negative CD bands at around 320 and 350 nm, respectively, indicating that the guest is embedded in the asymmetric locus of the CyD cavity. ¹H-NMR spectroscopic studies suggested that the mono-substituted benzene ring of ebselen is preferably included in the cavity of SBE7--CyD. The results indicate that SBE7--CyD is useful as a solubilizing agent for ebselen.     

Study of Inclusion Complexes of Cyclodextrins with Orange II

Inclusion reactions of - and -CD with Orange IIwere measured by means of a stopped-flow method and UV-spectra. The forward rate constants (k₊), backward rateconstants (k_-) and the equilibrium constants (K) for the inclusion reactions were determined. Theinclusion processes of CD with Orange II follow a one-step reaction mechanism. The value of the forward rate constantat neutral and alkaline conditions for Orange II binding to -CD cavity was large. This suggests that thenaphthalene side is partially included in the final complex form. In the case of -CD, only marginal differenceis shown.It is probable that inclusion covers the whole naphthalene group and part of the azo group as well,resulting ina small effect from the pH variation. The results show that the equilibrium constant at pH 7 for the binding ofOrange II to -CD is the largest because the included part of Orange II matches the cavity of -CD well.     

Inclusion Complexes of Cyclodextrins with 4-Amino-1,8-Naphthalimides

The formation of inclusion complexes between 4-amino-1,8-naphthalimides and cyclodextrins (CDs) was investigated. The naphthalimides used in the study were 4-amino-1,8-naphthalimide (I) and4-(2-phosphonoethylamino)-N-(2-phosphonoethyl)-1,8-naphthalimide,tetraethylester (II). The CDs employed were -CD, -CD, -CD, HP--CD, HP--CD andHP--CD (HP = hydroxypropyl). Evidence for complex formation was obtained from the changes in the fluorescence spectra of the dyes in the presence of increasing amounts of the CDs. The most striking changes were observed with HP--CD and HP--CD. Treatment of the data using Benesi–Hildebrand plotswas consistent with a 1:1 inclusion model. The determined stabilityconstants were (K_eq, M^-1): 106 (I:HP--CD, pH = 2.0), 193 (I:HP--CD, pH = 7.0), 113 (I:HP--CD, pH = 7.0), 155(II:HP--CD, pH = 2.0), 121 (II:HP--CD,pH = 7.0), 301 (II:HP--CD, pH = 7.0). It can beconcluded that compound I forms a more stable complex with HP--CD than with HP--CD. Compound II, on the other hand, forms a more stable complex with HP--CD than with HP--CD.     

水溶液中环糊精包结物的包结常数的测定方法

环糊精（CD）是由6，7，8个葡萄糖基构成的环状化合物，分别叫做α、β、γ-CD，它们具有“外亲水，内疏水”的独特性质，可以与多种物质形成包结物，而改变物质的特性，因而被广泛应用于各行各业中，在以往研究的基础上，总结了多种测定环糊精包结常数的方法，以便能更好地研究并开发利用具有极大潜力的环糊精。     

Fast Atom Bombardment Mass Spectroscopic Investigation of Inclusion Complexes of Cyclodextrins with 4-Nitrophenol and Benzoic Acid

Mixtures of -, -, and -cyclodextrins and 4-nitrophenol (or benzoic acid) were investigated by means of fast atom bombardment mass spectroscopy. In the gas phase, inclusion complexes of -, , and -cyclodextrins with 4-nitrophenolate and benzoate, which have a 1 : 1 cyclodextrin–guest stoichiometry, were observed in negative-ion mode. In addition, guest anions, clusters of two and three guest molecules, and guest–matrix complexes were observed.     

Interaction of Nonaromatic Amino Acids with Cyclodextrins in Aqueous Solution

Weak interactions of nonaromatic amino acids with - and -cyclodextrins in aqueous solutions at 298.15 K were studied calorimetrically. The structure and solvation of these compounds noticeably affect the thermodynamic characteristics of interparticle interactions.     

Paramagnetic Relaxation Enhancements in Acetate and Its Fluorine Derivatives Interacting with Gd3+: Complex Formation,Structure, and Transmetallation

The relative spatial distribution and motion with respect to Gd³⁺ of the ¹H and ¹⁹F nuclei in the acetate ion and its fluorine derivatives are studied in D₂O solutions through the paramagnetic relaxation rate enhancements (PREs) of these nuclei. We derive general theoretical expressions of the longitudinal PRE in terms of the analytical concentrations of metal and ligands, formation constants of the complexes, metal–nucleus distances, and coordination lifetimes of the ligands. The observed formation constants of the 1 metal: 1 ligand complexes markedly decrease with increasing number of fluorine atoms, the electronegativity of which reduces the negative partial charge of the coordinating COO^? group. The coordination lifetimes are very short at the scale of the relaxation times of the protons of metal bound acetate, that is, shorter than about 10 μs. The average distance of the acetate protons from Gd³⁺ is in fair agreement with independent crystallographic determination. The release of free Gd³⁺ from the very stable Gddtpa (dtpa=diethylene‐triaminepentaacetate) complex caused by the competition of Zn²⁺ for dtpa, is evidenced by an increase of the PREs with Zn²⁺ concentration. The observed PRE increase is consistent with the known equilibrium constants governing the speciation involving Gd³⁺, Zn²⁺, and dtpa. The present case study illustrates a method which easily yields experimental tunable properties suitable to test the ongoing theories of lanthanide Ln³⁺ complexation in solution.     

Spectroscopic Characterization and Properties of Some Bioactive- Peroxovanadium Complexes in Aqueous Solution

1　ＩＮＴＲＯＤＵＣＴＩＯＮＰｅｒｏｘｏｖａｎａｄｉｕｍ ( ｐＶ )ｃｏｍｐｌｅｘｅｓａｒｅ ｐｏｔｅｎｔｐｒｏｔｅｉｎｔｙｒｏｓｉｎｅｐｈｏｓｐｈａｔａｓｅｉｎ ｈｉｂｉｔｏｒｓｗｉｔｈｉｎｓｕｌｉｎ ｍｉｍｅｓｉｓｐｒｏｐｅｒｔｉｅｓａｎｄｃｏｕｌｄｐｏｓｓｉｂｌｙｂｅｄｅｖｅｌｏｐｅｄｉｎｔｏａｎｅｗｋｉｎｄｏｆｏｒａｌｄｒｕｇｆｏｒｔｈｅｔｒｅａｔｍｅｎｔｏｆｄｉａｂｅｔｅｓ[1～ 3].Ｒｅｃｅｎｔｌｙ ,ｔｈｉｓｋｉｎｄｏｆｃｏｍｐｏｕｎｄｈａｓｒｅｃｅｉｖｅｄｃｏｎｓｉｄｅｒａｂｌｅａｔｔｅｎｔ…     

Preparation and Properties of Inclusion Compounds of Cyclodextrins with Organotransition Metal Complexes

Inclusion compounds of transition metal complexes of cycloocta-1,5-diene (cod) and norbornadiene (nbd) with cyclodextrins were prepared. Two-to-one (cyclodextrin:guest) inclusion compounds were obtained in high yields by the treatment of β-cyclodextrin (β-CD) with [(L)RhCl]₂ (L = nbd or cod) and 1:1 inclusion compounds were obtained by the reaction of β-CD with (cod)PtX₂ (X = Cl, Br, or I) in high yields, while γ-CD formed 1:1 inclusion compounds with (cod)PtX₂ (X = Br or I). The formation of inclusion compounds is selective. α-CD did not form inclusion compounds with any transition-metal complexes with cycloocta-1,5-diene. Thermogravimetric measurements show that the complexes are stabilized by inclusion in cyclodextrin cavities. The inclusion compounds were characterized by ¹ H-NMR, IR, UV, and circular dichroism spectra.     

Quantitative Raman Analysis of Carotenoid Protein Complexes in Aqueous Solution

Carotenoids are naturally abundant, fat-soluble pigmented compounds with dietary, antioxidant and vision protection advantages. The dietary carotenoids, Beta Carotene, Lutein, and Zeaxanthin, complexed with in bovine serum albumin (BSA) in aqueous solution, were explored using Raman spectroscopy to differentiate and quantify their spectral signatures. UV visible absorption spectroscopy was employed to confirm the linearity of responses over the concentration range employed (0.05–1 mg/mL) and, of the 4 Raman source wavelengths (785 nm, 660 nm, 532 nm, 473 nm), 532 nm was chosen to provide the optimal response. After preprocessing to remove water and BSA contributions, and correct for self-absorption, a partial least squares model with R² of 0.9995, resulted in an accuracy of the Root Mean Squared Error of Prediction for Beta Carotene of 0.0032 mg/mL and Limit of Detection 0.0106 mg/mL. Principal Components Analysis clearly differentiated solutions of the three carotenoids, based primarily on small shifts of the main peak at ~1520 cm⁻¹. Least squares fitting analysis of the spectra of admixtures of the carotenoid:protein complexes showed reasonable correlation between norminal% and fitted%, yielding 100% contribution when fitted with individual carotenoid complexes and variable contributions with multiple ratios of admixtures. The results indicate the technique can potentially be used to quantify the carotenoid content of human serum and to identify their differential contributions for application in clinical analysis.     

抗抑郁化合物SIPI5358与环糊精形成的非共价复合物

用电喷雾电离质谱(ESI-MS)和串级质谱(MS/MS),并结合紫外光谱、荧光光谱等方法,研究一种芳烷醇哌嗪类抗抑郁化合物SIPI5358与α-、β-、γ-环糊精(CD)制备得到的非共价复合物.质谱分析结果显示,SIPI5358分子可以和α-CD生成配合比为1∶1的非共价复合物,而与β-、γ-CD生成不同配合比的非共价复合物.串级质谱的结果进一步验证β-CD与SIPI5358非共价复合物的组成.用紫外光谱和荧光光谱实验对液相中非共价复合物的形成进行了辅助研究,结果均再次验证了非共价复合物的生成.荧光光谱实验测得SIPI5358与β-CD反应的生成常数Kf=3.45×103 mol.L-1.     

A New Tetracycle from Dimerization of the N-Methylpyridazinium Ion in Aqueous Solution

In a one-pot synthesis at room temperature the N-methylpyridazinium ion ( 1 ) dimerizes stereospecifically and with 100 % conversion in a series of OH⁻-catalyzed processes to give a new tetraazafluorene ( 2 ). Four of the individual steps can be identified directly and monitored by ¹H NMR spectroscopy.     

Inclusion Complexes of Cyclodextrins with Tetrakis(4-carboxyphenyl)porphyrin and Tetrakis(4-sulfonatophenyl)porphyrin in Aqueous Solutions

In neutral and alkaline solutions, tetrakis(4-carboxyphenyl)porphyrin (TCPP) and tetrakis(4-sulfonatophenyl)porphyrin (TSPP) form 1:1 and 2:1 host–guest inclusion complexes with -cyclodextrin (-CD), -cyclodextrin (-CD), and 6-deoxy-6-diethylamino--CD (DEA--CD), except for DEA--CD in alkaline solution. On the other hand, TCPP and TSPP form only 1:1 inclusion complexes with 6-deoxy-6-dihexylamino--CD (DHA--CD). The limited solubilities of DEA--CD in alkaline solution and DHA--CD are likely responsible for no observation of the 2:1 inclusion complex containing DEA--CD in alkaline solution and that containing DHA--CD. The equilibrium constants (Ks) of TCPP and TSPP for the formation of the inclusion complexes have been estimated from the absorption and/or fluorescence intensity changes in neutral and alkaline solutions. The K₂ values, which are the equilibrium constants for the formation of the 2:1 host–guest inclusion complex from the 1:1 inclusion complex, are about one tenth the corresponding K₁ values, except for the -CD–TSPP system in alkaline solution. In neutral solution, where DEA--CD and DHA--CD are in protonated forms, the electrostatic force operates between DEA--CD (DHA--CD) and TCPP (TSPP), leading to the greater K values than those in alkaline solution, where DEA--CD and DHA--CD exist as neutral species.     

Inclusion Modes of Berberine with β-Cyclodextrin in Aqueous Solution

The possible inclusion modes of berberine(Berb)with β-cyclodextrin(BCD)in aqueous solution were predicted by molecular docking,molecular dynamics(MD)simulation and binding free energy calculations.Firs...     

Simulation of 59Co NMR Chemical Shifts in Aqueous Solution

⁵⁹Co chemical shifts were computed at the GIAO‐B3LYP level for [Co(CN)₆]^3?, [Co(H₂O)₆]³⁺, [Co(NH₃)₆]³⁺, and [Co(CO)₄]^? in water. The aqueous solutions were modeled by Car–Parrinello molecular dynamics (CPMD) simulations, or by propagation on a hybrid quantum‐mechanical/molecular‐mechanical Born–Oppenheimer surface (QM/MM‐BOMD). Mean absolute deviations from experiment obtained with these methods are on the order of 400 and 600 ppm, respectively, over a total δ(⁵⁹Co) range of about 18 000 ppm. The effect of the solvent on δ(⁵⁹Co) is mostly indirect, resulting primarily from substantial metal–ligand bond contractions on going from the gas phase to the bulk. The simulated solvent effects on geometries and δ(⁵⁹Co) values are well reproduced by using a polarizable continuum model (PCM), based on optimization and perturbational evaluation of quantum‐mechanical zero‐point corrections.     

Stability,Morphology, and Effects of In Vitro Digestion on the Antioxidant Properties of Polyphenol Inclusion Complexes with β-Cyclodextrin

Polyphenols are inversely associated with the incidence of chronic diseases, but therapeutic use is limited by poor stability and bioaccessibility. Encapsulation has been shown to overcome some of these limitations. A selection of polyphenols (catechin, gallic acid, and epigallocatechin gallate) and their combinations were encapsulated in beta-cyclodextrin (βCD). Encapsulation was characterized and the thermal and storage stability was evaluated using the 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. The samples were then subjected to in vitro digestion using a simple digestion (SD) model (gastric and duodenal phases) and a more complex digestion (CD) model (oral, gastric, and duodenal phases). Thereafter, the chemical (oxygen radical absorbance capacity assay) and cellular (dichlorofluorescein diacetate assay in Caco-2 cells) antioxidant and antiglycation (advanced glycation end-products assay) activities were determined. Inclusion complexes formed at a 1:1 molar ratio with a high encapsulation yield and efficiency. Encapsulation altered the morphology of the samples, increased the thermal stability of some and the storage stability of all samples. Encapsulation maintained the antioxidant activity of all samples and significantly improved the antiglycation and cellular antioxidant activities of some polyphenols following SD. In conclusion, the formed inclusion complexes of βCD with polyphenols had greater storage stability, without altering the beneficial cellular effects of the polyphenols.     

Novel Hydrazone‐Based Tripodal Sensors: Single Selective Colorimetric Chemosensor for Acetate in Aqueous Solution

A series of novel tripodal colorimetric anion sensors based on hydrazone CHN NH groups have been synthesized and their recognition behavior with anionic guests has been studied. In DMSO solutions, sensors 1 and 2 show colorimetric responses for F⁻, H₂PO⁻₄ and AcO⁻, while in DMSO/H₂O (9:1, V/V) solutions, sensor 1 shows single selectivity for AcO⁻. ¹H NMR titration confirms that the tripodal sensors could bind anions through the collaboration of three hydrazone groups and anions residing in the central cavity of the sensors.     

A Study of b-Cyclodextrin Inclusion Complexes with Progesterone and Hydrocortisone Using Rotating Frame Overhauser Spectroscopy

Summary.  Inclusion complexes of β-cyclodextrin with two steroid derivatives, progesterone (pregn-4-ene-3,20-dione) and hydrocortisone (11,17,21-trihydroxy-pregn-4-ene-3,20-dione), were studied in the liquid state by NMR spectroscopy. The complex formation process was monitored by intermolecular dipolar interactions between ¹H signals in the hydrophobic β-cyclodextrin cavity (H-3 and H-5 of the α-glucose units) and the steroid moiety in ROESY spectra. The data revealed that progesterone is fully immersed in the β-cyclodextrin cavity; however, complete inclusion of the hydrocortisone molecule was prevented by the polar hydroxyl groups on its surface. Received April 26, 2001. Accepted (revised) May 18, 2001