Spectroscopic investigation of β-cyclodextrin -metoprolol tartrate inclusion complexes

Aqueous-solution complexes of β-cyclodextrin (β-CD) with metoprolol tartrate (MET) have been analysed with ¹H NMR and UV–vis spectroscopy. With ¹H NMR a [1:1] stoichiometry could be established for the β-CD-MET complex while its stability constant was determined with UV–vis spectroscopy. Powder diffraction data of a polycrystalline sample of the β-CD-MET complex show that a novel product has been formed, likely to be a β-CD-MET [1:1] inclusion complex. Also Hyperchem MM+ molecular-dynamics results suggest an inclusion complex and from ¹H NMR data it is inferred that probably the MET is docked in the CD with the formers methoxyethyl-benzene moiety in front. Mihaela Toma is Socrates/Erasmus student at UNED Madrid     

Preparation and spectral investigation on inclusion complex of beta-cyclodextrin with rutin

Solid inclusion complex of rutin with beta-cyclodextrin (beta-CD) was prepared by coprecipitate method. The formation of inclusion complex was confirmed by differential scanning calorimetry (DSC) and X-ray diffraction. The formation constant was obtained by steady-state fluorescence measurements and the result suggested the complex preferred 1:1 (rutin:CD) stoichiometry. Furthermore, the spatial configuration of the complex has been proposed based on NMR and molecular modeling.     

Synthesis and characterization of beta-cyclodextrin inclusion complex containing di(8-hydroxyquinoline) magnesium

The beta-cyclodextrin (beta-CD) inclusion complex containing di(8-hydroxyquinoline)magnesium was prepared. The product was characterized by NMR, IR, differential thermal thermogravimetric analysis (DT-TGA), spectrofluorimetry, and elemental analysis, indicating the formation of inclusion complex in which the quinoline rings of the guest were encapsulated within the beta-CD cavities. The Job's method provided 2:1 stoichiometry for the inclusion complex between beta-CD and di(8-hydroxyquinoline)magnesium. The association constant calculated with the modified Benesi-Hildebrand equation at 25 degrees C was determined. And the mean association constant was 3577 (L/mol)2, R.S.D. was 2.58%. The thermal stability and solubility of di(8-hydroxyquinoline)magnesium were improved when forming inclusion complex.     

Inclusion complex of 2-naphthylamine-6-sulfonate with beta-cyclodextrin: intramolecular charge transfer versus hydrogen bonding effects

The photophysical characteristics of the ground and excited states of 2-naphthylamine-6-sulfonate (2-NA-6-S) were investigated in different solvents and in beta-cyclodextrin (beta-CD). The spectral shifts are well correlated with Kamlet-Taft relationship. Multiple linear regression analysis indicated that both non-specific dipolar interaction and specific hydrogen bonding interactions play competitive roles in determining the position of the absorption maximum, while the dipolar interaction is the dominating parameter in determining the emission maximum. For the Stokes shift, both the nonspecific interaction and the hydrogen donation property of the solvent are participating equally. The molecular encapsulation of 2-NA-6-S by beta-CD in aqueous solution has been studied by different spectroscopic techniques. Fluorescence measurements show that the dielectric constant of beta-CD experienced by the included 2-NA-6-S is intermediate between water and methanol. The changes observed in the absorption and fluorescence spectra of 2-NA-6-S upon inclusion in beta-CD allowed the association constant to be calculated and found to be 465+/-100 and 495+/-100 M-1, respectively. The changes observed for the chemical shifts of 2-NA-6-S and beta-CD 1H NMR spectra and the corresponding 1H NMR spectra of their mixture confirmed the formation of the inclusion complex and showed that 2-NA-6-S is encapsulated in beta-CD cavity in a tilted equatorial approach.     

Host-guest interaction of L-tyrosine with beta-cyclodextrin

The inclusion complexes of beta-cyclodextrin (beta-CD) with l-tyrosine (l-TYN) were investigated by using spectrophotometers. The absorption and fluorescence enhancement occurs with beta-CD and l-TYN forms 1:1 inclusion complex. The unusual blue shift of hydroxyl ion in the beta-CD medium confirms OH groups present in the interior part of the beta-CD cavity and -COOH group present in the upper part of the beta-CD cavity. A mechanism is proposed to explain inclusion process. The inclusion interaction was examined and the thermodynamic parameters of inclusion process DeltaG, DeltaH and DeltaS were determined. The results indicated that the inclusion process was an exergonic and spontaneous process. Stable solid inclusion complexes were established and characterized by FT-IR, scanning electron microscope (SEM) methods.     

High Resolution NMR Spectroscopic Study of Complexation of Hydroxyzine Hydrochloride with β‐Cyclodextrin in Aqueous Solution

Hydroxyzine hydrochloride forms two 1:1 inclusion complexes with β‐cyclodextrin in aqueous solution as confirmed by the ¹H NMR titration and ROESY studies. One complex is formed by the deep penetration of the chlorophenyl ring from the wider rim side, while the mode of entry of the phenyl ring into the β‐CD cavity is not clear. The stoichiometry and overall association constant of the complexes have been determined by the treatment of ¹H NMR shift data. Some chiral discrimination by the host between the two enantiomers of hydroxyzine hydrochloride is also indicated.     

Possibilities and limitations of synchrotron X-ray powder diffraction with double crystal and double multilayer monochromators for microscopic speciation studies

The performance of a combined microbeam X-ray fluorescence/X-ray powder diffraction (XRF/XRPD) measurement station at Hamburger Synchrotronstrahlungslabor (HASYLAB) Beamline L is discussed in comparison to that at European Synchrotron Radiation Facility (ESRF) ID18F/ID22. The angular resolution in the X-ray diffractograms is documented when different combinations of X-ray source, optics and X-ray diffraction detectors are employed. Typical angular resolution values in the range 0.3–0.5° are obtained at the bending magnet source when a ‘pink’ beam form of excitation is employed. A similar setup at European Synchrotron Radiation Facility beamlines ID18F and ID22 allows to reach angular resolution values of 0.1–0.15°. In order to document the possibilities and limitations for speciation of metals in environmental materials by means of Hamburger Synchrotronstrahlungslabor Beamline L X-ray fluorescence/X-ray powder diffraction setup, two case studies are discussed, one involved in the identification of the crystal phases in which heavy metals such as chromium, iron, barium and lead are present in polluted soils of an industrial site (Val Basento, Italy) and another involved in the speciation of uranium in depleted uranium particles (Ceja Mountains, Kosovo). In the former case, the angular resolution is sufficient to allow identification of most crystalline phases present while in the latter case, it is necessary to dispose of an angular resolution of ca. 0.2° to distinguish between different forms of oxidized uranium.     

NMR spectroscopic study of the inclusion complex of desloratadine with β-cyclodextrin in solution

Desloratadine (DES) is an antihistamine used in the treatment of allergies and chronic urticaria. ¹H NMR spectroscopic study of varying ratios of DES and β-Cyclodextrin (β-CD) in D₂O suggests the formation of a 1:1 inclusion complex formed by the penetration of Cl-substituted aromatic ring into the β-CD cavity. The stoichiometry and binding constant of the complex were determined by Scott’s method.     

Infrared spectroscopy of racemic and enantiomeric forms of atenolol

The molecular structure of conformational isomorphs given by X-ray diffraction for racemic and enantiomeric atenolol were optimized at the HF/6-31G* level of theory and the infrared spectra of the structure were calculated. These spectra are used to characterize the differences between the various atenolol conformers. The spectra of the (R,S)- and S-atenolol solid forms were recorded and the bands corresponding to the functional groups identified with the aid of the calculated spectra, fitting analysis, temperature effect and H/D isotopic exchange. Particular attention was paid to the stretch vibration modes of the functional groups present in the atenolol.     

Spectral properties and inclusion of 3-(4'-dimethylaminophenyl)-1-(2-furanyl)prop-2-en-1-one in organized media of micellar solutions, beta-cyclodextrin and viscous medium

On the line of a previous work on the spectral properties of some of heteroaryl chalcone, the absorption and fluorescence emission spectral properties of 3-(4'-dimethylaminophenyl)-1-(2-furanyl)prop-2-en-1-one (DMAFP), have been investigated in organized media of aqueous micellar and beta-cyclodextrin (beta-CD) solutions. While the absorption spectra are less sensitive to the nature of the added surfactant or beta-CD, the characteristics of the intramolecular charge transfer (ICT) fluorescence are highly sensitive to the properties of the medium. The ICT maximum is strongly blue-shifted with a great enhancement in the fluorescence quantum yield on adding micellar or beta-CD. This indicates the solubilization of DMAFP in the micellar core and formation of an inclusion complex with beta-CD. The critical micelle concentrations (CMC) as well as the polarity of the micellar core of SDS, CTAB and TX-100 have been determined. The CMC values are in good agreement with the reported values while the polarity is lower indicating that DMAFP molecules are incorporated in the micellar core not at the micellar interface. The inclusion constants of binding of DMAFP in micellar or beta-CD have been also determined. The thermodynamic parameters of formation of DMAFP:CD inclusion complex have been calculated from the temperature dependence of the fluorescence spectra of the formed complex. The highly negative value of formation entropy (DeltaS=-98.0Jmol(-1)K(-1)) reflects the high restrictions imposed on the movement of both the host and included guest molecules which is consistent with the increase of the fluorescence yield and blue shift of the fluorescence maximum.     

Spectral characteristics of tramadol in different solvents and β-cyclodextrin

Effect of solvents and β-cyclodextrin on the absorption and fluorescence spectra of tramadol drug has been investigated and compared with anisole. The solid inclusion complex of tramadol with β-CD is investigated by FT-IR, ¹H NMR, scanning electron microscope (SEM), DSC and semiempirical methods. The thermodynamic parameter (ΔG) of inclusion process is determined. A solvent study shows (i) the spectral behaviour of both tramadol and anisole molecules is similar to each other and (ii) the cyclohexanol group in tramadol is not effectively conjugated with anisole group. However, in β-CD, due to space restriction of the CD cavity, a weak interaction is present between the above groups in tramadol. β-Cyclodextrin studies show that tramadol forms 1:2 inclusion complex with β-CD. A mechanism is proposed for the inclusion process.     

Spectroscopic study and antioxidant properties of the inclusion complexes of rosmarinic acid with natural and derivative cyclodextrins

Measurement of total antioxidant activity/capacity of polyphenols in various solvent media necessitates the use of cyclodextrins to solubilize lipophilic antioxidants of poor aqueous solubility. The inclusion complexes of the slightly water soluble antioxidant, rosmarinic acid (RA), with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), 2-hydroxyethyl-β-cyclodextrin (HE-β-CD), and methyl-β-cyclodextrin (M-β-CD) were investigated for the first time. The effect of cyclodextrins (CDs) on the spectral features of RA was measured in aqueous medium using UV-vis and steady-state fluorescence techniques by varying the concentrations of CDs. The molar stoichiometry of RA-CD inclusion complexes was verified as 1:1, and the formation constants of the complexes were determined from Benesi-Hildebrand equation using fluorescence spectroscopic data. Among the CDs, maximum inclusion ability was measured in the case of M-β-CD followed by HP-β-CD, HE-β-CD, β-CD and α-CD. Solid inclusion complexes were prepared by freeze drying, and their functional groups were analyzed by IR spectroscopy. Antioxidant capacity of CD-complexed rosmarinic acid was measured to be higher than that of the lone hydroxycinnamic acid by the CUPric Reducing Antioxidant Capacity (CUPRAC) method. The mechanism of the TAC increase was interpreted as the stabilization of the 1-e oxidized o-catechol moiety of RA by enhanced intramolecular H-bonding in a hydrophobic environment provided by CDs, mostly by M-β-CD.     

Structures and crystal chemistry of the double perovskites Ba2LnB′O6 (Ln=lanthanide B′=Nb and Ta): Part I. Investigation of Ba2LnTaO6 using synchrotron X-ray and neutron powder diffraction

The structure of 14 compounds in the series Ba₂LnTaO₆ have been examined using synchrotron X-ray diffraction and found to undergo a sequence of phase transitions from I2/m monoclinic to I4/m tetragonal to cubic symmetry with decreasing ionic radii of the lanthanides. Ba₂LaTaO₆ is an exception to this with variable temperature neutron diffraction being used to establish that the full series of phases adopted over the range of 15-500 K is P2₁/n monoclinic to I2/m monoclinic to rhombohedral. The chemical environments of these compounds have also been investigated and the overbonding to the lanthanide cations is due to the unusually large size for the B-site in these perovskites.     

Unusual spectral shifts on fast violet-B and benzanilide: Effect of solvents, pH and β-cyclodextin

The absorption and fluorescence spectra of fast violet-B (FVB) and benzanilide (BA) have been analysed in different solvents, pH and β-cyclodextrin. The inclusion complex of FVB with β-CD is investigated by UV–visible, fluorimetry, AM 1, FTIR and SEM. The absorption maximum of FVB (anilino substitution) is red shifted than that of BA, but the benzoyl substitution hardly changed the ground state structure of BA. Compared to BA, the emission maxima of FVB largely blue shifted in cyclohexane and aprotic solvents, but red shifted in protic solvents and the longer wavelength maxima in FVB is due to the intramolecular charge transfer (TICT). In BA, the normal emission originates from a locally excited state and the longer wavelength band due to intramolecular proton transfer in non-polar/aprotic solvents and in protic solvents it is due to TICT state. β-CD studies reveal that, FVB forms 1:2 complex from 1:1 complex and BA forms 1:2 complex with β-CD.     

In silico strategies to describe the formation of the inclusion complex between β-cyclodextrin and β-naphtyloxyacetic acid: a preliminary step towards prediction of log K

Ligand/cyclodextrin is a peculiar type of ligand/receptor system. We report the results of a docking procedure using β-naphtyloxyacetic acid as ligand and various models of β-cyclodextrin as receptor. The results indicate that docking strategies can successfully be applied to any ligand/cyclodextrin system with the final aim of predicting log K values.     

High Performance Liquid Chromatographic Enantioresolution of Benzoyl Amino Acid,Dipeptides and Tripeptide on β-Cyclodextrin Bonded Stationary Phase Using Polar-Organic Acetonitrile as the Mobile Phase

The enantiomeric resolution of several dipeptides, amino acid (i.e., isoleucine) and tripeptide (i.e., Leu-Gly-Phe) with two stereogenic centers on β-cyclodextrin bonded chiral stationary phase (β-CD CSP) using polar-organic acetonitrile as the mobile phase is examined through pre-column chemical derivatization with a series of tagging reagents such as benzoyl chloride, benzenesulfonyl chloride and 1-naphthalenesulfonyl chloride. These tagging reagents are similar in structure; however, the enantioselectivity for the same analyte derivatized with these tagging reagents is quite different and found to be the best with benzoyl chloride. In the reversed-phase mode or on the γ-CD CSP under the same chromatographic conditions, the enantioresolution diminishes for all tagged enantiomers that were examined in this study. Dipeptides derivatized by benzoyl chloride appear to be better resolved than by dansyl chloride as reported previously. Interestingly, no enantioresolution for most derivatized amino acids with single stereogenic center was observed. Finally, enantioresolution can be enhanced by replacing the basic additive such as triethylamine with tripropylamine in the polar-organic mobile phase.     

UV–vis absorption properties of polyazomethine in base and protonated with 1,2-(di-2-ethylhexyl)ester of 4-sulfophthalic acid form

The UV–vis absorption properties of undoped and doped 1,4-phenylenemethylidynenitrilo-1,4-phenylenenitrilomethylidyne (PAZ) in various temperatures are reported. It is demonstrated that the absorption spectra can be modified not only by changing the temperature from 193 K to 413 K, but also via acid–base doping involving the protonation of nitrogen atom in imine group. The use of special protonating agent, i.e. 1,2-(di-2-ethylhexyl)ester of 4-sulfophthalic acid (PSA) lead to the modification of the absorption spectrum of the PAZ. The imine band in UV–vis spectrum of the doped with the PSA polyazomethine is 85 nm red shifts in comparison with unprotonated one. The thermochromism of PAZ included the conformational changes in the conjugating backbone structure of the undoped and doped polyazomethine.     

Preparation of inclusion complex between polyaniline and β‐cyclodextrin in aqueous solution

Two routes have been developed inorder to prepare an inclusion complex of polyaniline (PANI) and β‐cyclodextrin (βCyD). The first route was to in situ polymerize N‐phenyl‐1,4‐phenylenediamine (PPD) which was encapsulated in βCyD in advance. The formation of an inclusion complex was confirmed by UV‐vis, circular dichroism (CD), and NMR spectra. It was found that the synthesized complex was readily dissolved in a range of solvents due to the solubility of βCyD. In these solvents, PANI was well encapsulated by βCyD with some conformation change in the chain of PANI, which was proved by the CD spectra of PANI. The second route involved preparing the inclusion complex by post‐encapsulation of PANI emeraldine base (EB) into βCyD in aqueous solution at room temperature. The encapsulation of EB into βCyD was confirmed by FT‐IR and UV‐vis spectra. The band shift in UV‐vis spectra indicated that the inclusion complexation was a gradual process, and the change in the chain conformation of PANI was also observed after it was encapsulated into βCyD. Copyright © 2003 John Wiley & Sons, Ltd.     

NMR spectroscopic characterization of inclusion complexes comprising cyclodextrins and gallated catechins in aqueous solution: cavity size dependency

The structure of inclusion complexes of γ‐cyclodextrin (γ‐CD), (–)‐gallocatechin gallate (GCg), and (–)‐epigallocatechin gallate (EGCg) in D₂O was investigated using several NMR techniques. GCg formed a 1:1 inclusion complex with γ‐CD in which the A and C rings of GCg were inserted deep at the head of the A ring into the γ‐CD cavity from the wide secondary hydroxyl group side. In the 1:1 inclusion complex with GCg and γ‐CD, the GCg moiety maintained a conformation in which the B and B′ rings of GCg took both pseudoequatorial positions with respect to the C ring. The structure of the inclusion complex of GCg and γ‐CD obtained from NMR experiments supported well that determined from PM6 semiempirical SCF MO calculations. However, ¹H NMR experiments suggested that EGCg did not form any inclusion complex with γ‐CD in D₂O. The marked difference between GCg and EGCg in inclusion behavior toward γ‐CD may be explained in terms of the stabilization energy calculated with the PM6 method. Copyright © 2008 John Wiley & Sons, Ltd.     

Hydroxypropyl chitosan bearing beta-cyclodextrin cavities: synthesis and slow release of its inclusion complex with a model hydrophobic drug

Hydroxypropyl chitosan-graft-carboxymethyl beta-cyclodextrin (HPCH-g-CM beta-CD) was synthesized by grafting CM beta-CD onto HPCH using water soluble 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as the condensing agent. Due to the presence of hydrophobic beta-CD rings onto the HPCH backbone, this polymer can be used as a matrix for controlled drug release. The adsorption of a hydrophobic model drug, ketoprofen, by HPCH-g-CM beta-CD microparticles (using tripolyphosphate as an ionic crosslinking agent) fitted well in the Langmuir isotherm equation. The drug dissolution profile showed that HPCH-g-CM beta-CD microparticles provided a slower release of the entrapped ketoprofen than chitosan, and the release behavior was influenced by the pH value of the medium. These results suggest that beta-CD grafted with chitosan derivatives may become a potential biodegradable delivery system to control the release of hydrophobic drugs with pH-responsive capability.