Synthesis of a novel β-cyclodextrin derivative with high solubility and the electrochemical properties of ferrocene-carbonyl-β-cyclodextrin inclusion complex as an electron transfer mediator

A facile strategy for preparing water-soluble β-cyclodextrin derivative, carbonyl-β-cyclodextrin, was developed by partial oxidation of β-cyclodextrin. The solubility of carbonyl-β-cyclodextrin was greatly enhanced due to the breaking of intramolecular hydrogen bond network of β-cyclodextrin. Ferrocene was included into the cavity of carbonyl-β-cyclodextrin to form Fc-carbonyl-β-cyclodextrin inclusion complex. The electrochemical properties of Fc-carbonyl-β-cyclodextrin were studied. The Fc-carbonyl-β-cyclodextrin complex exhibited high solubility and was shown to be good electrochemical probe and efficient mediator for bioelectrocatalysis of glucose oxidase. The bioelectrocatalytic efficacy of Fc-carbonyl-β-cyclodextrin complex opened up homogeneous applications of ferrocene in amperometric biosensor systems.     

Characterization of the inclusion complex of β-cyclodextrin with sorbic acid in the solid state and in aqueous solution

Crystal structure of β-cyclodextrin (β-CD) complexes with sorbic acid, usually as food preservative, has been determined by single-crystal X-ray diffraction at 113 K. The space group of β-cyclodextrin-sorbic acid complex is P1 with unit cell dimensions of a = 15.284(3) Å, b = 15.402(3) Å, c = 17.981(4) Å, α = 99.67(3)°, β = 112.83(3)°, γ = 102.48(3)° and Z = 1. The result indicates that the β-CD molecules form head-to-head dimers which pack in the intermediate mode. Each dimer contains two guest molecules whose methyl groups are located at the dimer interface while the carboxyl groups protrude from the β-CD primary faces. Water molecules (25.5) are distributed outside the cyclodextrin cavity over 31 sites. Furthermore, nuclear magnetic resonance spectroscopy (¹H NMR) has been employed to investigate the inclusion behavior between the host β-CD and guest sorbic acid in aqueous solution. The results obtained enabled us to structurally characterize the β-CD inclusion complex with sorbic acid.     

Characterization of β-cyclodextrin inclusion complex with procaine hydrochloride by 1H NMR and ITC

The inclusion of local anesthetic drug procaine hydrochloride by β-cyclodextrin was investigated by 1D and 2D proton NMR spectroscopy and isothermal titration calorimetry (ITC) at 298 K. The stoichiometry of the complex was determinate by the method of continuous variation, using the chemical induced shift of both host and guest protons. The association constant K, of the obtained complex was calculated and found to be 293.17 M^?1. Rotating frame NOE spectroscopy, was used to ascertain the solution geometry of the host–guest complex. The result reveals that the procaine molecule penetrates into the β-cyclodextrin cavity with the aromatic ring. The energetics of complexation process is investigated by ITC technique. The analysis indicates that the complexation of procaine by β-CD is an exothermic process and show that both enthalpy and entropy contribute to the binding process. The obtained value for the association constant is in good agreement with that obtained from NMR.     

Synthesis and characterization of inclusion complex of the vasodilator drug minoxidil with β-cyclodextrin

The inclusion complex of β-cyclodextrin and minoxidil (2,4-diamino-6-piperidinopyrimidine 3-oxide) was synthesized using two methods—kneading and freeze-drying—and characterized by UV-Vis spectroscopy, infrared spectroscopy, powder X-ray diffractometry, differential scanning calorimetry, thermal gravimetric analysis, and nuclear magnetic resonance spectroscopy. These techniques have demonstrated the existence of inclusion compound formation between the host and guest with a molar ratio of 1:1. The studies of solubility and the data obtained by nuclear magnetic resonance spectroscopy showed a weak interaction between the guest and the cyclodextrin molecules in solution.     

Phase solubility and FTIR-ATR studies of idebenone/sulfobutyl ether β-cyclodextrin inclusion complex

The favourable accessibility offered by sulfobutyl ether β-cyclodextrin (SBE-β-CD) for the complexation with idebenone (IDE) has been probed, as a function of temperature, in liquid state, by phase solubility study, and, in solid state, by FTIR-ATR technique. The phase solubility results indicated the formation of a IDE/SBE-β-CD inclusion complex with 1:1 molar ratio (A_L type diagram), whose apparent stability constants at T = 300, 310, and 320 K have been estimated according to the Higuchi–Connors method. The formation of the inclusion complex has been confirmed on a freeze-dried and a co-precipitated product by FTIR-ATR spectroscopy, monitoring the changes induced by complexation on some characteristic vibrational bands of IDE. Quantitative studies, performed in a wide T range, from T = 250 K to T = 340 K, allowed us to extract information on the effect of temperature on the different hydrogen-bonded environments involving host, guest, and crystallization water molecules. Again, complexation is proved to enhance the stability of the guest, at least in the explored T range.     

Solid state characterization of the inclusion complex of valsartan with methyl β-cyclodextrin

In this work, we illustrate the usefulness of cyclodextrins, namely, methyl-β-cyclodextrin (MβCD), an amorphous, methylated derivative of the natural β-cyclodextrin, as a tool to form an inclusion complex with Valsartan (VAL), a poorly water soluble drug. The phase solubility study showed A_L type of curve with slope less than one indicating the formation of complexes in 1:1 molar ratio of drug and CD. The stability constant was found to be 538.14 ± 5.4 Mole^?1. Solid binary systems between VAL and MβCD were prepared experimentally in a stoichiometry 1:1 by different techniques (physical mixing, kneading, co-evaporation). Afterward these products were characterized by Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), Scanning electron microscopy (SEM) and ¹H Nuclear magnetic resonance study (¹H NMR). The results obtained suggested that co-evaporation methods yield a higher degree of amorphous entities suggesting the formation of inclusion complex between VAL and MβCD. The dissolution of VAL from the binary systems was studied to select the most appropriate system for the formulation development. It was concluded that the preparation technique played an important role in the dissolution behavior of the drug and the inclusion complex between VAL and MβCD obtained by co-evaporation method allowed better performance.     

Excimer fluorescence and structures of the inclusion complexes of β-cyclodextrin with naphthalene and its derivatives

Fluorescence of the inclusion complexes with different compositions formed by naphthalene-h₈, naphthalene-d₈, 2,7-dimethylnaphthalene (DMN), and 2-benzylnaphthalene (BN) with β-cyclodextrin (β-CD) in water was studied. Two types of fluorescence are observed, monomer (MF) and excimer (EF_ fluorescence. The excimer fluorescence of the 2∶2 complex emitted by aggregated light-dispersing crystals forming a precipitate, whereas is the MF is concentrations, EF predominates for the resulting complexes. A proposed structure of the inclusion complexes was derived from MNDO/PM3 semiempirical quantum-chemical calculations. The EF is caused by the structure of the complex, in which both naphthalene molecules are separated by a distance of 4.7 Å: they lie in parallel orientation to each other, whereby one ring is displaced from the other by one-fourth of the length of the naphthalene ring. The complexes of 2,7-DMN and 2-benzylnaphthalene with β-CD do not exhibit EF. For the 2∶2 complex of 2,7-DMN with β-CD, this is due to the fact that the aromatic fragments are removed too far from one another 2-Benzylnaphthalene is unable to form an inclusion complex with β-CD, in whose structure the aromatic fragments inside the cavity could be arranged in parallel planes; instead, it forms a 1∶2 complex with β-CD.     

The structural analysis of the inclusion complex of β-cyclodextrin with m-nitrophenoxyacetic acid

The inclusion complex of β-cyclodextrin with m-nitrophenoxyacetic acid was studied by single crystal X-ray diffraction,2D NMR spectroscopy and semi-empirical methods AMI.The crystallographic study shows that two β-cyclodextrins are held together by hydrogen bonds to form head-to-head dimers.The disordered guest molecule adjusts itself to attain the most stable accommodation into the cavity in which the nitro group is located at the dimer interface while the carboxyl group is buried in the primary hydroxyl groups of β-cyclodextrin.The guest inside the cavity is disordered over two sites and exhibits mobility.Moreover,2D NMR spectroscopy and theoretical study show the same inclusion behavior.In comparison to the inclusion complex of β-cyclodextrin with p-nitrophenoxyacetic acid,the host-guest stoichiometries are different,i.e.,2:1 for m-nitrophenoxyacetic acid and 1:1 for p-nitrophenoxyacetic acid,while the inclusion orientation and the packing pattern of the host are similar in both complexes.     

Electrochemical and associated techniques for the study of the inclusion complexes of thymol and β-cyclodextrin and its interaction with DNA

Journal of Solid State Electrochemistry - Thymol, a potent agent for microbial, fungal, and bacterial disease, has low aqueous solubility and it is genotoxic, i.e., is capable of damaging...     

Spectroscopic investigation of interaction of 6-methoxyflavanone and its β-cyclodextrin inclusion complex with calf thymus DNA

The interaction of 6-methoxyflavanone (6MF, 6-methoxy-2-phenyl-4H-1-benzopyran-4-one) with calf thymus DNA (ctDNA) was investigated by absorption spectroscopy, fluorescence spectroscopy, and cyclic voltammetry in the presence and absence of ??-cyclodextrin (??-CD) acting as capping agent. Molecular modelling was used to optimise the study of 6MF-??-CD and 6MF-DNA interactions. Enhancement in the fluorescence intensity of 6MF was observed due to the formation of 1 : 1 complex with ??-CD. In the presence and absence of DNA, 6MF showed different characteristics such as hyperchromic effect, red shift of absorption spectra and fluorescence quenching of 6MF due to binding between 6MF and ctDNA. The nature of the binding group was found to be different for the 6MF-ctDNA and 6MF-ctDNA-??-CD systems. An increase in fluorescence intensity was observed for the 6MF-ctDNA system while varying the concentration of ??-CD due to encapsulation of a part of 6MF in cyclodextrin. The results are compatible with the possibility of the interaction of dihydrobenzopyran-4-one moiety of 6MF with ctDNA as well as with ??-CD. Cyclic voltammetric studies confirmed the binding interaction between 6MF and ctDNA in the absence and presence of ??-CD and molecular modelling explains the site of the interaction of 6MF with cyclodextrin and ctDNA.     

Preparation and characterization of the inclusion complex of baicalein with γ-cyclodextrin: an antioxidant ability study

The formation of the complex of Baicalein with γ-cyclodextrin (γ-CD) was studied by UV–Vis absorption spectroscopy, fluorescence spectra and nuclear magnetic resonance spectroscopy (NMR) in solution. The solid inclusion complex of Baicalein with γ-CD was synthesized by the co-precipitation method. The characterization of the solid inclusion complexes have been proved by infrared spectra. The formation constant (K) of complex was determined by fluorescence method. The results suggested that in different pH solutions, γ-CD has different inclusive capacity to different forms of Baicalein. γ-CD was most suitable for inclusion in neutral media. In addition, the experimental resulted confirmed the existence of 1:1 inclusion complex of Baicalein with γ-CD. Kinetic studies of DPPH? with Baicalein and γ-CD complex were done. The results obtained indicated that the Baicalein/γ-CD complex was the most reactive form. Special configuration of complex has been proposed on NMR technique.     

Preparation and properties of inclusion compound of cyclopentadienylmanganese tricarbonyl complex with a ß-cyclodextrin dimer

The host-guest inclusion compound of cyclopentadienylmanganese tricarbonyl (guest) with ß-cyclodextrin dimer (host) bridged with two 1,2-diaminoethane has been prepared as the first example of cyclodextrin dimer inclusion compounds with organotransition metal complexes and characterized by elemental analysis and IR spectra as well as thermogravimetric analysis. The manganese complex included in the dimer is thermally more stable than the free complex. ¹H NMR spectroscopy has established that the cyclopentadienylmanganese complex and the dimer form an inclusion compound in aqueous solution with a stability constant (β₂, 195 mol⁻²l²) at 22°C. The spectroscopic studies and the results of elemental analysis revealed that stoichiometry (1:2, host: guest) of the inclusion compound in water is identical to its stoichiometry in solid state.     

Preparation and characterization of theβ-cyclodextrin inclusion complex with sulfafurazole

The 1 : 1 inclusion complex involving sulfafurazole (SF) and-cyclodextrin (-CD) is prepared by the freeze-drying method and characterized on the basis of its chemical analysis, thermal behavior, infrared spectrum, X-ray powder pattern and¹³C NMR spectrum in DMSO-d₆ solution. The stability constant of the inclusion complex was determined by the solubility method. The effect of cyclodextrin on the UV absorption spectrum of sulfafurazole was also observed.     

Investigation of the inclusion complex of tolfenamic acid with β-cyclodextrin: Geometry and NBO analysis

Quantum chemical calculations were carried out to investigate geometry and driving forces for inclusion complexes of tolfenamic acid (TA) into β-CD (at 1:1 stoichiometry). Two possible orientations of TA in the β-CD cavity were considered. Both PM3MM and ONIOM2 method evidence that TA is encapsulated in the β-CD cavity for A and B orientation. Finally, charge transfer between the donor and acceptor orbitals of each TA and β-CD play an important role to stabilize the inclusion complex.     

Pharmacology and structures of the free base of the anaesthetic kazcaine and its complex with β-cyclodextrin

The base form of the local anaesthetic kazcaine (BFK, [1-(2-ethoxyethyl)-4-ethynyl-4-benzoyloxypiperidine, C₁₈H₂₃NO₃]) and β-cyclodextrin (β-CD) co-crystallized as BFK:β-CD inclusion complex in 1:2 M ratio from a mixture of water and ethanol while the filtered mother liquor yielded crystals of free BFK. X-ray diffraction showed that the crystals of BFK and its inclusion complex with β-CD belong to monoclinic (P2₁/c) and triclinic (P1) space groups, respectively. The crystals of free BFK are stabilized by pairs of C–H?O, C–H?π and ≡C–H?O type interactions and van der Waals contacts. In the 1:2 BFK:β-CD complex the two β-CD molecules are in hydrogen-bonding contact with their primary hydroxyl groups, the 1-(2-ethoxyethyl)-4-ethynyl-piperidine moiety being located in one and the benzoyloxy group of BFK in the other β-CD. This crystal structure is of the channel-type, the β-CD molecules of the 1:2 BFK:β-CD complex interacting with their secondary hydroxyl groups. The pharmacological activities of the 1:2 BFK/β-CD inclusion complex have been determined in mice, rats, porpoises and rabbits and compare favourably with those of kazcaine, procaine, dicaine, lidocaine and trimecaine. The methods used include terminal (superficial), infiltration, conduction anaesthesia, and acute toxicity.     

Investigation on the inclusion behaviour of baicalein with β-cyclodextrin and derivatives and their antioxidant ability study

The formation of the complexes of baicalein (Ba) with β-cyclodextrin (β-CD) and β-CD derivatives (HP-β-CD and Me-β-CD) was studied by UV–vis absorption spectroscopy, fluorescence method, nuclear magnetic resonance spectroscopy and phase-solubility measurement. The solid–inclusion complexes of Ba with CDs were synthesised by the co-precipitation method. The characterisations of the solid–inclusion complexes have been proved by infrared spectra and differential scanning calorimetry. Experimental conditions including the concentration of various CDs and media acidity were investigated in detail. The results suggested that the inclusion ratio of HP-β-CD with Ba was the highest among the three kinds of CDs. The binding constants (Ks) of the inclusion complexes were determined by fluorescence method and phase-solubility measurement. Kinetic studies of DPPH√ with Ba and CDs complexes were also done. The results indicated that the Ba/HP-β-CD complex was the most reactive form.     

Preparation and evaluation of inclusion complexes of diacerein with β-cyclodextrin and hydroxypropyl β-cyclodextrin

The objective of this research was to improve the aqueous solubility, dissolution rate and, consequently, bioavailability of diacerein, along with avoiding its side effect of diarrhea, by complexation with β-cyclodextrin (β-CD) and HP-β-cyclodextrin (HP-β-CD). Phase solubility curve was classified as an A_N type for both the CDs, which indicated formation of complex of diacerein with β-CD and HP-β-CD in 1:1 stoichiometry and demonstrating that both CDs are proportionally less effective at higher concentrations. The complexes were prepared by kneading method and were evaluated to study the effect of complexation on aqueous solubility and rate of dissolution in phosphate buffer (pH 6.8). Based on the dissolution profile HP-β-CD was selected for preparing fast disintegrating tablet of diacerein which was compared with marketed formulation (MF-J). The HP-β-CD complex was probed for Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction studies which evidenced stable complex formation and increase in amorphousness of diacerein in complex. In brief, the characterization studies confirmed the inclusion of diacerein within the non-polar cavity of HP-β-CD. HP-β-CD complex showed improved in vitro drug release profile compared to pure drug and similar to that of marketed formulation respectively.