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.     

Inclusion complexes with cyclodextrin and usnic acid

Molecular inclusion complexes of usnic acid (UA) with β-cyclodextrin (β-CD) and 2-hydroxypropyl β-cyclodextrin (HP β-CD) were prepared by the co-precipitation method in the solid state in the molar ratio of 1:1. Structural complexes characterization was based on different methods, FTIR, ¹H NMR, XRD and DSC. Parallel to the complex by the above methods, corresponding physical mixtures of UA with cyclodextrins and complexing agents (β-CD, HP β-CD and UA) were analyzed. The results of DSC analysis showed that, at around 200 °C, the endothermal peak in the complexes with cyclodextrins originating from the UA melting has disappeared. Complex diffractogram patterns do not contain peaks characteristic for the pure UA. They are more appropriate to cyclodextrin diffractogram. This fact points to the molecular encapsulation of UA in the cyclodextrin cavity. Chemical shifts in ¹H NMR spectra after the inclusion of UA into the cyclodextrin cavity, especially H-3 protons (0.0012 and 0.0102 ppm in the β-CD and HP β-CD, respectively) and H-5 and H-6 (0.0134 ppm) and hydrogen from CH₃ (0.0073 ppm) HP β-CD also points to the formation of molecular inclusion complexes. The improved solubility of UA in water was achieved by molecular incapsulation. In the complex with β-CD the solubility is 0.3 mg/cm³, with HP β-CD 4.2 mg/cm³ while the uncomplexed UA solubility is 0.06 mg/cm³. The microbial activity of UA and both complexes was tested against eight bacteria and two fungi and during the test no reduced activity of UA in the complexes was observed.     

Synthesis of β-cyclodextrin-lysozyme conjugates and their physicochemical and biochemical properties

Recently a great interest in the field of protein engineering and the design of innovative drug delivery systems employing specific ligands such as cyclodextrins is observed. The paper reports the solid state, thermal method for protein coupling with β-cyclodextrin and the physicochemical and biological properties of the obtained conjugates. The structure of the obtained conjugates was investigated via liquid chromatography-mass spectrometry, dynamic light scattering and circular dichroism analysis. The presented conjugates were biologically active and covalently bound β-cyclodextrin preserved the ability to form inclusion complexes with the model compound. This report demonstrates the great potential of cyclodextrin as a modifying unit that can be used to modulate the properties of therapeutic proteins, additionally giving such conjugates the possibility to transport many therapeutic substances in the form of inclusion complexes. In addition, the paper presents the potential of protein-cyclodextrin conjugates to construct innovative bioactive molecules for biological and medical applications.     

A study on the potential interaction between cyclodextrin and lipoxygenase

To get a more complete view on the lipoxygenase (LOX) catalysis in presence of cyclodextrin, the investigation into the interaction between cyclodextrins (CDs) and LOX was carried out. Effects of cyclodextrins on the activity and structure of LOX were explored in this work. It is confirmed that inhibition effect induced by complexation of CDs and LOX plays a leading role in inhibition factors of LOX catalysis in presence of CDs. Inhibition of β-cyclodextrin on LOX depended on concentration and tended to be intensified with the increase of β-CD. The enhancement of intrinsic fluorescence of LOX induced by β-CD was detected, which was probably due to the formation of complexes between aromatic amino acid residues of LOX and β-CD. The results of circular dichroism assay indicated that β-CD altered the secondary structure and microenvironment of LOX which was responsible for inhibition of enzyme catalysis.     

Effect of cyclodextrins on the physicochemical properties of chlorophyll a in aqueous solution

The interactions between chlorophyll a and two beta-cyclodextrins, that have the same cavity size but different substituents, were studied in aqueous solutions. These supramolecular host-guest complexes were examined by a combination of UV/vis absorption, circular dichroism, NMR, and steady-state and time-resolved fluorescence measurements. The results indicate that all cyclodextrins solubilize the pigment mainly in monomeric form in water. The pigment forms 1:1 complexes with the heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin and 1:2 complexes with the hydroxypropyl-beta-cyclodextrin. In such complexes the methyl groups of the cyclodextrin inner cavity are involved in the interaction with the pigment as evidenced by NMR measurements. We also measured the luminescence of singlet oxygen photosensitized by chlorophyll a in the inclusion complexes.     

Induced Circular Dichroism Spectra of β- and γ-Cyclodextrin Complexes with Indazolinone and Related Compounds

The magnetic circular dichroism (MCD) spectra of indazolinone, isatine, and 3-iminoisoindolinone and the induced circular dichroism (ICD) spectra of the inclusion complexes with β- or γ-cyclodextrins (CDs) have been measured. The spectra are interpreted by results of the ZINDO calculations. In the presence of cyclodextrin, the OH indazolinone tautomer is main structure that is consistent with that in the DMSO solution. The structures of the inclusion complexes are very different because of the scale of the cavity of cyclodextrin or position of quinone in molecules.     

Complex Formation of Polybutadiene with Cyclodextrins

Polybutadienes were found to form inclusion complexes with cyclodextrins in high selectivity to give crystalline compounds. α‐Cyclodextrin and β‐cyclodextrin form complexes only with polybutadienes of low molecular weight and high 1,4‐addition content. Polybutadienes with high 1,2‐content gave complexes with γ‐cyclodextrin in low yield. The yields of the γ‐cyclodextrin complexes decreased with increasing molecular weights of the polybutadienes of similar composition. Complexes were isolated and characterized by means of FT‐IR, ¹H NMR, ¹³C CP/MAS NMR, ¹³C PST/MAS NMR spectroscopies, and X‐ray diffraction. Inclusion modes are discussed.     

Fluorescence Studied of Dissociation Constant of Cyclodextrin With Phenol Derivatives

α-and β-cyclodextrins consisting of six and seven glucose residues respectively, have lipophilic cavities with different inner diameters. They form host-guest inclusion complexes with hydrophobic organic and organometallic guest molecules in aqueous solution. These host-guest complexes have proved to be excellent model systems for studying the nature of noncovalent bonding forces in aqueous media. They have provided valuable insights into the hydrophobic effect and London dispersion forces and are good model for understanding the specificity of enzyme substrate interactions [1] Evidence for the formation of inclusion complexes have been provided from calovimetric titration [2] NMR[33], circular dichroism[4], U V[1] and fluorescence spectra[5] and conductometric method[6] etc. H ere we report a new fluorimetric method for a study on the reaction of the host-guest inclusion complexes of cyclodextrin with phenols. Dissociation constants (Kd) of the inclusion complexes of some phenols with α-β-cyclodextrin are estimated based on the variation of the fluorescent intensity and modified Harad' equations.     

Binding behaviors of scutellarin with α-, β-, γ-cyclodextrins and their derivatives

A series of cyclodextrin/scutellarin inclusion complexes were prepared from α-cyclodextrin, β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin with scutellarin (SCU), and their inclusion complexation behaviors, such as stoichiometry, complex stability constants and inclusion mode, were investigated by means of UV/Vis spectroscopy, ¹H NMR and 2D NMR. The results showed that the SCU could be efficiently encapsulated in the cyclodextrin cavity in aqueous solution to produce complexes that were more soluble than free SCU. The enhanced binding ability of cyclodextrins towards SCU was discussed from the viewpoint of the size/shape-fit and multiple recognition mechanism between host and guest.     

Equilibrium and structural characterization of ofloxacin–cyclodextrin complexation

The enantiomer-specific characterization of ofloxacin–cyclodextrin complexes was carried out by a set of complementary analytical techniques. The apparent stability constants of the ofloxacin enantiomers with 20 different cyclodextrins at two different pH values were determined to achieve good resolution capillary electrophoresis enantioseparation either to establish enantioselective drug analysis assay, or to interpret and design improved host–guest interactions at the molecular level. The cyclodextrins studied differed in the nature of substituents, degree of substitution (DS), charge and purity, allowing a systematic test of these properties on the complexation. The seven-membered beta-cyclodextrin and its derivatives were found to be the most suitable hosts. Highest stability and best enantioseparation were observed for the carboxymethylated-beta-cyclodextrin (DS ~ 3.5). The effect of substitution pattern (SP) was investigated by molecular modeling, verifying that SP greatly affects the complex stability. Induced circular dichroism was observed and found especially significant on carboxymethylated-beta-cyclodextrin. The complex stoichiometry and the geometry of the inclusion complexes were determined by ¹H NMR spectroscopy, including 2D ROESY techniques. Irrespective of the kind of cyclodextrin, the complexation ratio was found to be 1:1. The alfa-cyclodextrin cavity can accommodate the oxazine ring only, whereas the whole tricyclic moiety can enter the beta- and gamma-cyclodextrin cavities. These equilibrium and structural information offer molecular basis for improved drug formulation.     

Induced Circular Dichroism Spectra of β- and γ-Cyclodextrin Complexes with Indazolinone and Related Compounds

The magnetic circular dichroism (MCD) spectra of indazolinone, isatine, and 3-iminoisoindolinone and the induced circular dichroism (ICD) spectra of the inclusion complexes with β- or γ-cyclodextrins (CDs) have been measured. The spectra are interpreted by results of the ZINDO calculations. In the presence of cyclodextrin, the OH indazolinone tautomer is main structure that is consistent with that in the DMSO solution. The structures of the inclusion complexes are very different because of the scale of the cavity of cyclodextrin or position of quinone in molecules.This revised version was published online in July 2005 with a corrected issue number.     

Inhibition of cyclodextrins on the activity of α-amylase

α-amylase activity influences both flour fermentation process and the quality of the fermented products due to its ability of breaking starch into smaller units. The inhibition of cyclodextrins on α-amylase activity was investigated in this paper. Experiment results showed that hydrophobic cavity size was an intrinsic factor during the inhibition processing. Among three types of cyclodextrin (α-, β- and γ-), β-type exhibited the most significant inhibitory activity toward α-amylase. The optimal inhibitory parameters were indicated to be pH 5.9, concentration of β-cyclodextrins 1 mmol/L, reaction temperature 45 °C and reaction time 60 min. Results suggested that the endogenous fluorescence of α-amylase was inhibited by cyclodextrins. Circular dichroism spectrum indicated that the secondary structure of α-amylase, including α-helices, β-sheets and random coils, was changed by cyclodextrins. All the results in this paper aim to provide a further understanding for α-amylase in the industry application.     

Ruthenium and Osmium Podate Cyclodextrins with Dual-function Recognition Sites for Luminescent Sensing

A multifunctionalised podand cyclodextrin ligand, β-CD-(urebpy)⁷, with urea--bipyridine binding sites leads to ruthenium and osmium, {Ru[β-CD-(urebpy)⁷]}[PF⁶]² {Os[β-CD-(urebpy)⁷]}[PF⁶]², cyclodextrins. The bipyridine ligands are preorganised by the cyclodextrin cavity encapsulating the ruthenium and osmium core to give photoactive metallocyclodextrins. The podate cyclodextrin complexes show characteristic ruthenium and osmium tri-bipyridine luminescence. It is demonstrated that the ruthenium cyclodextrins participate in sensing schemes through both the cyclodextrin cavity and the urea cage at the bottom of the cyclodextrin rim. Luminescence quenching of the ruthenium emission is observed by addition of anthraquinone guests in the cyclodextrin cavity or addition of dihydrogen phosphate anion.     

Complex Formation Between Poly(dimethylsilane) and Cyclodextrins

Poly(dimethylsilane)s form inclusion complexes with cyclodextrins in high selectivity to give crystalline compounds. β‐Cyclodextrin forms complexes with poly(dimethylsilane)s of low molecular weight only, γ‐cyclodextrin with poly(dimethylsilane)s of high molecular weight in high yield, and α‐cyclodextrin does not form complexes with poly(dimethylsilane) at all. Complexes were isolated and characterized by spectroscopic methods and X‐ray diffraction.     

Conformation of permethylated cyclodextrins and the host-guest geometry of their inclusion complexes

Macrocylic conformation of permethylated cyclodextrins and the geometry of their inclusion complexes were examined on the basis of the X-ray data of three permethylated -cyclodextrin complexes and two permethylated -cyclodextrin complexes. The host macrocyclic ring is remarkably distorted owing to steric hindrance involving the methyl groups and the inability to form intramolecular hydrogen bonds. The guest molecules are included within the host cavity, but their position and orientation are quite different from those found in the corresponding cyclodextrin complexes.     

Syntheses and characterisation of novel cyclodextrin vinyl derivatives from cyclodextrin-nitrophenol-derivatives

In this study novel reactive α-, β- and γ-cyclodextrin-esters (acrylate, pent-4-enoate and undec-10-enoate) have been synthesised and characterised. The syntheses were carried out by using nitrophenol-esters with the ability to form inclusion complexes with cyclodextrins, thereby aiming at a better control of the substitution degree and number of positional isomers of the cyclodextrin derivatives. Derivatives of α-, β- and γ-cyclodextrins modified with three different lengths of carbon-chains were successfully synthesised and characterised by MALDI-TOF MS, HPLC and LC-MS/MS, revealing some differences in LC elution patterns, substitution degrees and number of produced positional isomers. Differences were seen as an effect of changing the size of the cyclodextrin as well as the size of the side-chain being attached. The inclusion complexes between the nitrophenol esters and the different cyclodextrins were studied by ITC and selected ones by 2D ROESY NMR, showing some interesting differences in strength and structure of the complexes. These differences are speculated to be the origin of the different substitution patterns of the derivatives as observed by LC-MS/MS.     

Cyclodextrin Inclusion Compounds in Research and Industry

α-, β-, and γ-Cyclodextrins are cyclic oligosaccharides consisting of six, seven, or eight glucose units, which can be obtained on a large scale from starch. They form inclusion compounds with smaller molecules which fit into their 5—8 Å cavity. These (crystalline) complexes are of interest for scientific research as, contrary to the classical clathrates, they exist in aqueous solution and can be used to study the hydrophobic interactions which are so important in biological systems. Cyclodextrins also serve as models both for polymeric starch and, in the form of their polyiodide complexes, for “blue iodine-starch”. As cyclodextrins catalyze several chemical reactions they and their functionalized derivatives provide useful enzyme models. Cyclodextrins can be used to advantage in the production of pharmaceuticals, pesticides, foodstuffs, and toilet articles—the (micro-encapsulated) active and aromatic substances enclosed within them are protected from the effects of light and atmosphere and can be easily handled and stored in powder from. Substances which are not very soluble in water become more soluble in the presence of cyclodextrins—creams and emulsions can be stabilized, and the growth and yield of grain harvests can be increased. Cyclodextrins can be chemically modified for many different purposes; polymerized cyclodextrin or cyclodextrin bound to a polymer carrier have already been employed in gel inclusion and affinity chromatography.     

Spectroscopic investigation of the structures of dialkyl tartrates and their cyclodextrin complexes

Structures of three dialkyl tartrates, namely, dimethyl tartrate, diethyl tartrate, and diisopropyl tartrate, in CCl4, dimethyl sulfoxide (DMSO)/DMSO-d6, and H2O/D2O solvents have been investigated using vibrational absorption (VA), vibrational circular dichroism (VCD), and optical rotatory dispersion (ORD). VA, VCD, and ORD spectra are found to be dependent on the solvent used. Density functional theory (DFT) calculations are used to interpret the experimental data in CCl4 and DMSO. The trans-COOR conformer with hydrogen bonding between the OH group and the C=O group attached to the same chiral carbon is dominant for dialkyl tartrates both in vacuum and in CCl4. The experimental VA, VCD, and ORD data of dialkyl-D-tartrates in CCl4 correlated well with those predicted for dimethyl-(S,S)-tartrate molecule as both isolated and solvated in CCl4. In DMSO solvent, dialkyl tartrate molecules favor formation of intermolecular hydrogen bonding with DMSO molecules. Clusters of dimethyl-(S,S)-tartrate, with one molecule of dimethyl-(S,S)-tartrate hydrogen bonded to two DMSO molecules, are used for the DFT calculations. A trans-COOR cluster and a trans-H cluster are needed to obtain a reasonable agreement between the predicted and experimental data of dimethyl tartrate in DMSO solvent. VA, VCD, and optical rotations are also measured for dialkyl tartrate-cyclodextrin complexes. It is noted that these properties are barely affected by complexation of dialkyl tartrates with cyclodextrins, indicating weak interaction between tartrates and cyclodextrin. Binding constants of alpha-CD and beta-CD with diethyl L-tartrate in both H2O and DMSO have been determined using isothermal titration calorimetry technique. The smaller binding constants (less than 100) confirmed the weak interaction between tartrates and cyclodextrin in the solution state.     

Syntheses Characterization of Chloro-cyclopentadienyltricarbonyl-molybdenum with β-Cyclodextrin Supramolecular

Organotransition metal complex have been extensively used as homogeneous catalysts in organic reactions and much effort has been paid to improve their activity and selectively. Cyclodextrins have been studied as a model of enzyme for selective catalysis. However, so far there are only a few reports on the inclusion compounds of organometallic complexes with cyclodextrins. Breslow et al.repored high acylation rates for β-CD using ferrocene derivatives and assumed β-CD substrate complexes as intermediate [1]..larad et al reported the preparation and propertics of cyclodextrin-ferrocen inclusion compounds as the first example of cyclodextrin inclusion compounds of organotransition metal complexes[2]. Song Le-Xin et al reported the supramolecular inclusion compound of β-cyclodextrin with cyclopentadieny-tricarbonylmanganese [3] .To our knowledge, there are no reports of inclusion compounds of β-CD with molybdenum organometallic complexes. In the present work we described the preparation and properties of the supramolecular of CpMo(CO)3Cl with β-CD in details.     

Effect of the ring size and asymmetry of cyclodextrins on their inclusion ability: a theoretical study

Effect of the ring size and asymmetry upon methylation of cyclodextrins (CDs) on their inclusion ability has been demonstrated for the inclusion complexes of native α-, β-, γ-CDs, dimethylated β-CD (DIMEB) and trimethylated β-CD (TRIMEB) with piperazine (PIZ) by PM3 and ONIOM calculations. In all complexes, PIZ prefers residing mostly in the central CD cavity. The complex stability in the order TRIMEB–PIZ > DIMEB–PIZ > α-CD–PIZ > γ-CD–PIZ > β-CD–PIZ indicates that the CD-ring asymmetry promotes the macrocycle deformation and inclusion ability. Our calculation results suggest that the inclusion complexes of both native and methylated CDs with PIZ in the gas phase are energetically stable, in addition to the β-CD–PIZ inclusion complex that has been evidenced thus far by X-ray crystallographic and spectroscopic analyses. Further calculations in the presence of water and adjacent CD molecules show that the increased intermolecular hydrogen bond interactions enhance the stability of β-CD–PIZ complex.