Spectroscopic Study of the Inclusion Complexes of Phenylbutazone and Oxyphenbutazone with Cyclodextrins in Polar Reaction Media

The formation of inclusion complexes of -, -, hydroxypropyl-- (HP--) and -cyclodextrins with phenylbutazone and oxyphenbutazone has been studied in aqueous buffer solution (pH 7.5 and 0.1 mol dm^-3 NaCl), dimethylsulfoxide, and 25, 50 and 75% dimethylsulfoxide/water mixtures. These complexation reactions have been followed by UV electronic absorption spectroscopy. In addition, 1D and 2D ¹H NMR spectra were recorded to obtain structural information about the inclusion complexes formed in solution; 136 binding constant values were determined at five different temperatures (288, 293, 298, 303 and 310 K) from the electronic absorption data and, from these H_binding and S_binding values were obtained. At the studied cyclodextrin and guest concentration ranges, 1 : 1 inclusion complexes were detected. Only in three cases were 1 : 2 complexes detected, those of phenylbutazone and oxyphenbutazone with -cyclodextrin in aqueous, and oxyphenbutazone with hydroxypropyl--cyclodextrin in 75% dimethylsulfoxide/water solutions.     

Complexation of Ketoconazole by Native and Modified Cyclodextrins

Complexation of ketoconazole (KET), a broad-spectrum antifungal drug, with β- and γ-cyclodextrins (CDs), heptakis (2,6-di-O-methyl)-β-CD (2,6-DM-β-CD), heptakis (2,3,6-tri-O-methyl)-β-CD (TM-β-CD), 2-hydroxypropyl-β-CD (2HP-β-CD) and carboxymethyl-β-CD (CM-β-CD) was studied. The stability constants were determined by the solubility method at pH = 6 and for 2,6-DM-β-CD and CM-β-CD at pH = 5. At pH = 6, the stability constants increased in the order: TM-β-D < γ-CD < 2HP-β-CD < β-CD < CM-β-CD < 2,6-DM-β-CD. At pH = 5, due to the increased ionization of KET, the stability constant with CM-β-CD increased and with 2,6-DM-β-CD decreased. For complexes of KET with 2HP-β-CD and 2,6-DM-β-CD, the thermodynamic parameters of complexation were determined from the temperature dependence of the corresponding stability constants. For β–γ and TM-β-CD complexes, calculations using HyperChem 6 software by the Amber force field were carried out to gain some insight into the host–guest geometry.     

On Chloralose-Cyclodextrin Complexes by <Emphasis Type="Italic">ESI</Emphasis>-Mass Spectrometry

α-Chloralose is a useful mild anaesthetic, providing stable but not deep anaesthesia. Host–guest complexes of α-chloralose with α-, β- and γ-cyclodextrin (CD) were studied using electrospray ionisation (ESI-MS) mass spectrometry and molecular modelling (MD). As it is currently administered, chloralose is transported in a convenient water-soluble complex, and released to react on a physiological level with the reactor sites. It is believed that the chloraloses (α and its isomer β) are encapsulated within the CD cavity. However, the ESI spectra did not reveal such the presence of inclusion compounds. Searching of alternative mechanisms of transportation of these anaesthetic agents, we found that outer-cavity complexes of inserted chloraloses, as found from MD calculations, do have a reasonable stability.This revised version was published online in July 2005 with a corrected issue number.     

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.     

Electrochemical Study on Reactive Red 15 and its Interaction with Cyclodextrins

In this paper, the electrochemical behavior of the interaction of Reactive Brilliant Red K-2G (C.I. Reactive Red 15) with cyclodextrins in 0.1 mol · l⁻¹ NaCl (pH 6.9) has been studied by polarography and voltammetry. In a supporting electrolyte of NaCl (pH 6.9), a sensitive second derivative reduction peak (i _p ″) of Reactive Red 15 was found by linear sweep voltammetry (LSV). The peak potential is about −0.78 V (versus SCE). On the addition of CDs into the Reactive Red 15 solution, the reduction peak current (i _p ″) of Reactive Red 15 decreases and the peak potential (E _p ) shifts to a more positive potential. The study shows that Reactive Red 15 can form 1:1 inclusion complexes with nine CDs. The inclusion constants were calculated by “electric current method”. Furthermore, the inclusion ability of different kinds of cyclodextrins was compared, which provided some elemental data for application of Reactive Red 15 and cyclodextrins.     

Host–Guest Interactions of Risperidone with Natural and Modified Cyclodextrins: Phase Solubility, Thermodynamics and Molecular Modeling Studies

The solubility of risperidone (Risp) in aqueous buffered cyclodextrin (CD) solution was investigated for α-, β-, γ- and HP-β-CD. The effects of pH, ionic strength and temperature on complex stability were also explored. Neutral Risp tends to form higher order complexes (1:2) with both β- and HP-β-CD, but only 1:1 type complexes with α-, and γ-CD. The tendency of Risp to complex with cyclodextrins is in the order β-CD > HP-β-CD > γ-CD > α-CD. The 1:1 complex formation constant of Risp/HP-β-CD increases with increasing ionic strength in an opposite trend to the inherent solubility (S ₀) of Risp, thus indicating significant hydrophobic effect. The hydrophobic effect contributes to the extent of 72% towards neutral Risp/HP-β-CD complex stability, while specific interactions contribute only 4.7 kJ/mol. Thermodynamic studies showed that 1:1 Risp/HP-β-CD complex formation is driven by a favorable enthalpy change (ΔH ⁰=−31.2 kJ/mol, ΔS ⁰=−7 J/mol.K) while the 1:2 complex is largely driven by entropy changes (ΔH ⁰=−5.0 kJ/mol, ΔS ⁰=42 J/mol.K). Complex stability was found to vary with pH, with a higher formation constant for neutral Risp. Molecular mechanical computations using MM (atomic charges and bond dipole algorithms) and Amber force fields, which were carried out to explore possible sites of interactions between Risp and CDs and to rationalize complex stoichiometry, produced similar results concerning optimal inclusion complex geometries and stoichiometries.     

Formation of Inclusion Complexes between Cyclodextrins and Carbaryl and Characterization of the Complexes

The solubility of carbaryl increased with increasing concentrations of-CD, G₂--CD, and M--CD. The result suggests theformation of soluble inclusion complex. Solubility increase was highestin M--CD-carbaryl, being 18.4 fold higher than that of carbaryl when 100 mM M--CD was used. The apparent formation constant for the complex calculated from phase solubility diagram was 223.18 M^-1. The preparation of the complex in solid form for characterization was successful by kneading andfreeze-drying. The DSC curves for kneading and freeze-drying mixture didnot show the endothermic peak characteristic of carbaryl, but a small new endothermic peak was observed. FTIR analysis showed a shift of the major peak of carbonyl group in carbaryl molecule from 1717 to 1744 and 1734 cm^-1 in kneading and freeze-dried mixtures, respectively. M--CD-carbaryl complex demonstrated higher dissolution rate, higher thermal and UV stability but lower toxicity than its parent carbaryl compound.     

Spectroscopic and Molecular Docking Study of the Interaction between Neutral Re(I) Tetrazolate Complexes and Bovine Serum Albumin

Re(I) complexes have potential in biomedical sciences as imaging agents, diagnostics and therapeutics. Thus, it is crucial to understand how Re(I) complexes interact with carrier proteins, like serum albumins. Here, two neutral Re(I) complexes were used (fac-[Re(CO)₃(1,10-phenanthroline)L], in which L is either 4-cyanophenyltetrazolate (1) or 4-methoxycarbonylphenyltetrazole ester (2) , to study the interactions with bovine serum albumin (BSA). Spectroscopic measurements, calculations of thermodynamic and Förster resonance energy transfer parameters, as well as molecular modelling, were performed to study differential binding between BSA and complex 1 and 2 . Induced-fit docking combined with quantum-polarised ligand docking were employed in what is believed to be a first for a Re(I) complex as a ligand for BSA. Our findings provide a basis for other molecular interaction studies and suggest that subtle functional group alterations at the terminal region of the Re(I) complex have a significant impact on the ability of this class of compounds to interact with BSA.     

Synthesis of Highly Insulated Molecular Wires by Polymerization of Organic-Soluble Symmetrical Linked Inclusion Complex Monomers

Summary: We developed a new method for synthesizing an organic-soluble permethylated cyclodextrin-based insulated molecular wire (IMW); this method involves the polymerization of a symmetrical linked inclusion complex as a monomer. This monomer was synthesized by dimerization of linked inclusion complexes at the terminal alkynyl groups by Glaser coupling. The polyrotaxane thus obtained is highly soluble in a variety of organic solvents and has a high covering ratio, regioregularity, and photoluminescence efficiency.     

A Simulation on the Complexation of Cyclodextrins with Phospholipid Headgroups

The inclusion complexes of α-, β- and γ-cyclodextrin (CD) with three isolated phospholipid (PI – phosphatidylinositol; PS – phosphatidylserine; and PE – phosphatidylethanolamine) headgroups were studied using a flexible docking algorithm FDOCK based on molecular mechanics (CFF91 force filed). In the three phospholipid headgroups, PI headgroup exhibits the strongest affinity for CD, and the affinity of PS headgroup is greater than that of PE headgroup. By investigating the energy distribution and the complex structure in the inclusion procedure, it can be found that the van der Waals force is the main driving force responsible for the complexation. For the α-CD complex of PI headgroup, more than one inclusion complex should coexist due to the steric hindrance, which is reasonably consistent with the experimental results. Furthermore, analyses of the complex of PS and PE headgroup with α-CD also show that two or three possible complexes may appear in the inclusion process, and the complex structure with full inclusion is of the lowest energy and should be the most stable structure in the mixture. For β-␣and γ-CD, the energies of the most stable complexes structures for the three phospholipids headgroups were also discussed.     

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.     

Electroanalytical Method of Acid Blue 120 and its Supramolecular System with Cyclodextrins

In this paper, a simple, rapid, sensitive and accurate electroanalytical method of Acid Blue 120 (AB120) has been established by polarography. In a supporting electrolyte of 0.01 mol l⁻¹ Na₂HPO₄–KH₂PO₄ (pH 7.04) solution, a sensitive first derivative reduction peak (ip′) of AB120 was found by Linear Sweep Voltammetry (LSV). The peak potential is −820 mV (versus SCE). The peak current (ip′) is proportional to the concentration over the range 2.0 × 10⁻⁷–5.0 × 10⁻⁵ mol l⁻¹ (r=0.9961–0.9991) and the limit of detection (LOD) is 1.0 × 10⁻⁷ mol l⁻¹. The recovery of AB120 varied from 95.3 to 103.0% and the relative standard deviation (RSD) was 2.2% (n=8). The method has been expected to determination of wastewater in dye industry. In addition, the supramolecular system of AB120 with cyclodextrins has been studied. It can form 1:1 inclusion complex with six CDs. The inclusion constants were calculated and the inclusion ability of different kinds of CDs was compared. Furthermore, the inclusion mechanism was also preliminarily discussed, which provided some valuable information for further application of AB120 and CDs.     

Molecular Interactions and Thermodynamic Aspects of the Complexation Reaction between Gentian Violet and Several Cyclodextrins

The complexation process between gentian violet (CV+) and four different cyclodextrins (-, -, -, and HP--CDs) has been investigated under different reaction conditions (pH, solvent, and temperature) by electronic absorption and 1H NMR (NOE and NOESY) spectroscopies. All the binding constants were determined by the direct spectroscopic method. The H and S complexation values have been evaluated and discussed according to the diverse factors that affect the chemical interactions in these systems. A simple association takes place between the secondary hydroxyl or the hydroxypropyl groups of and HP--cycloamyloses, respectively, with the amine group of the gentian violet, while the binding between CV+ and - or -CDs corresponds to a real inclusion. Also, a CV22+ dimmeric species within the -CD cavity was detected in aqueous solution, while two molecules of -CD react with one molecule of gentian violet in DMSO at 294 K. In all the reaction media the -CD forms 1 : 1 complexes, but in the buffered aqueous solution at pH 7.5 the inclusion is deeper than in the other solvents. It is important to point out that the solvophobic effect is the most important binding factor in the complexation of the CV+ with the - and HP--CDs, while the complexes with -, and -cyclodextrins are mainly stabilized by van der Waals interactions between the guest and the host cavity. In all cases, the inclusion orientation is probably determined by the ion-dipole interactions between gentian violet and the solvent.     

环糊精-苯丙氨酸超分子体系的包合现象与分子识别

通过紫外-可见光谱探讨了水溶液中α-环糊精(CD 1),β-CD 2,七(2, 6-二-o-甲基)-β-CD 3和γ-CD 4与D-、L-、D,L-苯丙氨酸(Phe)形成超分子包合物的稳定常数(K)。手性或外消旋苯丙氨酸与同一主体结合能力的强弱顺序为:L- >D,L- >D-Phe,各体系的K_L/K_D值在1.65～3.01之间,给出了较好的异构体分离。但三种形式的苯丙氨酸与这些主体的缔合常数均较小(K< 3×10²mol·L^-1)。就不同主体而言,K值的次序为:3 >1 >4 >2,并不完全等同于K_L/K_D的顺序:2 >1 >3 >4。     

The Interaction of Piroxicam with Neutral (HP-β-CD) and Anionically Charged (SBE-β-CD) β-cyclodextrin

The interaction of piroxicam (PX) with sulfobutylether-β-cyclodextrin (SBE-β-CD) was studied by fluorescence spectroscopy and compared with that of hydroxypropyl-β-cyclodextrin (HP-β-CD). The stability constants (K) values for the PX-CDs complexes were obtained by steady-state fluorescence measurements. Inclusion conditions including concentrations of the two cyclodextrins and pH values were investigated for the complex formation in detail. The results suggested that the interaction of PX with charged CD (SBE-β-CD) is much stronger than that with uncharged CD (HP-β-CD) at any pH studied, in terms of a synergetic effect of hydrophobic and additional electrostatic interactions.     

A Cyclodextrin‐Based Photoresponsive Molecular Gate that Functions Independently of Either Solvent or Potentially Competitive Guests

The photoinduced interconversion between cinnamido‐substituted cyclodextrins constitutes a gating switch through which the substituent moves to open or block access to the cyclodextrin cavity. Most unusually for a cyclodextrin‐based device, the operation of this gate is solvent‐independent and unaffected by potentially competitive guests. It occurs in MeOH and DMSO, as well as in water. This contrasts with other cyclodextrin inclusion phenomena that are usually driven by hydrophobic effects and limited to aqueous media.     

Cations in a Molecular Funnel: Vibrational Spectroscopy of Isolated Cyclodextrin Complexes with Alkali Metals

The benchmark inclusion complexes formed by α‐cyclodextrin (αCD) with alkali‐metal cations are investigated under isolated conditions in the gas phase. The relative αCD‐M⁺ (M=Li⁺, Na⁺, K⁺, Cs⁺) binding affinities and the structure of the complexes are determined from a combination of mass spectrometry, infrared action spectroscopy and quantum chemical computations. Solvent‐free laser desorption measurements reveal a trend of decreasing stability of the isolated complexes with increasing size of the cation guest. The experimental infrared spectra are qualitatively similar for the complexes with the four cations investigated, and are consistent with the binding of the cation within the primary face of the cyclodextrin, as predicted by the quantum computations (B3LYP/6‐31+G*). The inclusion of the quantum‐chemical cation disrupts the C₆ symmetry of the free cyclodextrin to provide the optimum coordination of the cations with the ‐CH₂OH groups in C₁, C₂ or C₃ symmetry arrangements that are determined by the size of the cation.     

环糊精超分子包络物的相变行为及其热分析研究进展

本文概述了近年来国内外报道的关于环糊精(CD)超分子包络物的相变温度与热释出行为和主客体结构之间的关系.基于这些文献中热重、差示扫描量热和气相色谱耦合时间飞行质谱等方法提供的CD超分子包络物的热力学数据比较发现,在超分子包络物中CD与客体的相变温度及客体的释出形式依赖于客体被包结前的物相与主客体分子间相互作用的强度.客体的类型如:形态、结构、极性和体积等都会影响主客体之间的相互作用,进而导致包络物展现不同的相变和热释出温度.而且,主客体分子间的相互作用越强,超分子包络物的释出温度越高.     

A Theoretical Study on the Inclusion Complexation of Cyclodextrins with Inorganic Cations and Anions

PM3 and B3LYP/3-21+g(d) calculations were performed on theinclusion complexation of- and -cyclodextrin with inorganic cationsand anions includingLi⁺, Na⁺, F^-, and Cl^-. Both the gas-phase interaction and solvent effect weretaken into consideration. The CD complex with an anionwas more stable than that with acation, which was in agreement with the experimentalfindings. It was proposed thathydrogen bonding between the anion and the cyclodextrincavity was the physical origin ofsuch behavior.     

Circular Dichroism Study of the Inclusion-Dissociation Behavior of Complexes between a Molecular Nanotube and Azobenzene Substituted Linear Polymers

We have investigated the inclusion properties of molecular nanotubes composed ofcrosslinked -cyclodextrin. Induced circular dichroism was used to probe theformation and dissociation of complexes between the nanotubes and azobenzenemodified linear polymers. The polymer was poly(ethylene glycol) (PEG), either withor without a hydrophobic alkyl chain.It was found that the inclusion complex betweenthe nanotubes and polymers formed at room temperature, and that the polymers dissociated from the nanotubes with increasing temperature. Further, the polymer with hydrophobic alkyl chain was bound inside the nanotube more strongly and dissociated more abruptly with increasing temperature than its hydrophilic counterpart as expected theoretically.