Effect of pH and α-, β- and γ-cyclodextrin on the spectral properties of etoricoxib: spectroscopic and molecular dynamics study

The spectral properties of etoricoxib (ETR) at pH 2.0, 6.0 and 10.0 in the presence of cyclodextrins (CDs) were investigated. The absorption spectrum of ETR in acidic medium exhibited two bands centered at 236 and 273 nm, while in basic medium it exhibited two bands centered at 236 and 285 nm. No change in the spectrum was observed in the presence of CDs. The fluorescence emission spectra of ETR in acidic and basic media exhibited one band at 380 nm and another one at 484 nm. The emission band at 484 nm was enhanced when ETR was complexed with β-CD and γ-CD at pH 2.0, 6.0 and 10.0, while the band at 380 nm was enhanced selectively when ETR was complexed with α-CD at pH 2.0. Molecular dynamics simulations computations revealed that at pH 2.0, the sulfonyl moiety of H₂ETR²⁺ is preferentially included within the α-CD cavity, which is believed to cause the enhancement of the band at 380 nm. Moreover, at pH 6.0 and 10.0, the enhancement of the band at 484 nm was related to the inclusion of the chloropyridinyl and methylpyridinyl groups of the bipyridine moiety of HETR⁺ and ETR within β-CD and γ-CD cavities. Benesi–Hildebrand analysis showed that the ETR/β-CD complex adopts a 1:1 stoichiometry with association constant of K ₁₁?=?64.8 at pH 2.0, K ₁₁?=?105.4 at pH 6.0 and K ₁₁?=?520.5 at pH 10.0.     

A comparative study of the structure and properties of β-galactosidases

A comparative study of β-galactosidase amino acid sequences of E. coli and another four out of 11 microorganisms selected at the first stage was performed. It was shown that the functional amino acid residues in the catalytic domain and the ligand environment of the magnesium cation for all five sequences are identical. The mechanism of the catalytic action of E. coli and K. lactis β-galactosidases was investigated by the method of nucleophilic competition. It was shown that the mechanism of the effects of nucleophilic agents is kinetically identical both enzymes: the presence of methanol or butanediols affects the stage of degalactosylation; the presence of magnesium cations promotes the activity of both β-galactosidases; and the mechanisms of the thermal inactivation of E. coli and K. lactis β-galactosidases are different.     

Host-guest complex of nabumetone: β-cyclodextrin: quantum chemical study and QTAIM analysis

The aim of the present work is the investigation of the inclusion complex of nabumetone (NAB) and β-cyclodextrin (β-CD) using PM3, DFT, DFT-D and ONIOM2 methods. The results indicate that the most energetically favorable structure predicts a preference of the methoxy group to enter the cavity of β-CD from its wide rim. Consequently, the butanone moiety is positioned outside the cavity on the side of the secondary hydroxyls, with a total insertion of naphthalene group. The semi-empirical PM3 results are in good agreement with those obtained by the DFT optimization (with and without dispersion correction). The donor–acceptor interactions between drug and the cavity wall of the host, studied on the basis of natural bonding orbital (NBO) analysis, show the presence of weak intermolecular hydrogen bonds in addition to the most important van der Waals interactions. Furthermore, it is revealed that among the DFT and DFT-D techniques selected to quantify these interactions, WB97X-D functional provides the greatest values of stabilization energies E⁽²⁾. Finally, a detailed topological charge density analysis based on the quantum theory of atoms in molecules (QTAIM), developed by Bader and co-workers, has been accomplished using the WB97X-D and B3LYP methods on the most favorable complexes. A good correlation between the structural parameters and the electronic density is found.     

The physical properties and unusual pyrolysis behaviour of a supramolecular complex of β-cyclodextrin and potassium ferrioxalate

The thermal pyrolysis behaviour of a complex of β-cyclodextrin (CD) and potassium ferrioxalate (PF) was analyzed using gas chromatography coupled to time-of-flight mass spectrometry. Two rare inorganic ions: CO(2)(2+) and O(4)(+), neither of which was found in the cases of free β-CD and PF, were synchronously observed during the decomposition of the complex. Our observations led to proposed formation mechanisms of the ions, in which the structural transformation of a metastable intermediate ion (C(2)H(4)O(3)(+)) was employed to qualitatively explain our data. Besides this, the formation, structure and magnetic properties of the complex were evaluated carefully. First, XPS analysis indicates a decrease of electron densities of Fe(III) ions in the presence of β-CD. We think that this is due to an effect of the noncovalent complexation between PF and β-CD. This gives an indication on the effect of second sphere coordination of β-CD on the electronic structure of the Fe(III) in the first coordination sphere. Second, structural changes in stacking modes and morphologies provide further support for the noncovalent complexation. For example, the surface feature of the complex gives us an impression that both β-CD and PF are evenly dispersed with each other. Also, the complex presents a uniform sponge-like porous nanostructure with diameters of less than 50 nm. This seems to be an important reason for those changes that occurred in the thermal analysis. Finally, the result of magnetic experiments implies that the coordination compound PF upon complexation with β-CD will experience a gradual decrease in magnetization with the increase of magnetic fields. These observations have significant implications for a better understanding of the importance of the construction and deconstruction of a second sphere coordination in modifying the physical properties of an σ-coordination compound.     

Preparation and clay stabilization properties of cationic acrylamide polymer containing β-cyclodextrin

Research on Chemical Intermediates - In this study, a new family of short-chain cationic polymer, P(A-β-CD/AM/ATMAC), was synthesized via free radical-initiated aqueous system...     

Surface area and pore structure properties of urethane-based copolymers containing β-cyclodextrin

The surface area and pore structure characteristics were investigated for a series of aliphatic- and aromatic-based polyurethane (PU) copolymers containing a macromolecular porogen (β-cyclodextrin). The bi-functional diisocyanates used as crosslinker units were: 1,6-hexamethylene, 4,4'-dicyclohexylmethane, 4,4'-diphenylmethane, 1,4-phenylene, and 1,5-naphthalene diisocyanate, respectively. The macromolecular porogen content was controlled by fixing the composition of β-CD and varying the co-monomer mole ratio from unity to larger integer values. Nitrogen adsorption results reveal that copolymer materials with variable mole ratios (β-CD: crosslinker) from 1:1 to 1:3 displayed relatively low BET surface areas (SA～10(1) m(2)/g) and mesopore diameters (～16-29 nm). In contrast, a dye adsorption method in aqueous solution with p-nitrophenol (PNP) at pH=4.60 and 295 K provided estimates of the surface area (1.5-6.2×10(2) m(2)/g) for the corresponding copolymer materials. Variation of the copolymer SA was attributed to the type of diisocyanate crosslinker and its relative mole ratio. The differences in the estimated SA values from porosimetry and the UV-Vis dye adsorption method for these nanoporous copolymers were attributed to the role of solvent as evidenced by swelling of the copolymer framework in aqueous solution and the respective temperature conditions.     

Inclusion complex formation of β-cyclodextrin and Naproxen: a study on exothermic complex formation by differential scanning calorimetry

Inclusion complex formation between β-cyclodextrin and Naproxen was investigated using differential scanning calorimetry (DSC) as a function of the β-cyclodextrin-to-Naproxen molar ratio, ranging from 0:5:1 to 5:1. When these mixtures are heated above the melting temperature of Naproxen, an exothermic peak is observed at a temperature slightly higher than the melting peak of Naproxen. This peak, which has not been previously reported, has been interpreted as an exothermic energy of inclusion complex formation. The magnitude of this complex formation peak was found to be dependent upon the composition of the β-cyclodextrin and Naproxen mixture and increased in magnitude to a maximum value at a β-cyclodextrin:Naproxen molar ratio of 2:1. In addition, Naproxen recrystallization and re-melting peaks seen in the cooling and re-heating scans, respectively, decreased in magnitude with increasing molar ratio and totally disappeared for the mixture with 5:1 of β-cyclodextrin to Naproxen ratio indicative of complete inclusion of Naproxen in the cyclodextrin cavities. Complete inclusion was further reflected by the disappearance of key Naproxen peaks in Fourier transform infrared spectra of samples recovered from DSC experiments. The large excess of β-cyclodextrin needed to fully complex the Naproxen was found to be due to slow kinetics. Increasing the hold time after the initial melting led to inclusion efficiencies up to 95 % even for the 2:1 mixture. These experiments suggest that ratios of β-cyclodextrin:Naproxen 2:1 or greater facilitate the process by increasing the presence of cyclodextrin molecules in the close proximity of the drug molecules and lead to high inclusion efficiencies.     

Volumetric study on the inclusion complex formation of α- and β-cyclodextrin with 1-alkanols at different temperatures

The partial molar volumes (V_a) of 1-alkanols (carbon number, m=5, 6, 7) in - and -cyclodextrin (CD) solutions at 5.00 mmol kg^–1 have been determined as a function of alkanol concentration (C_a) between 293.2 and 308.2 K by using a dilatometer. It has been observed that with an increase in C_a, V_a increased in -CD solution but decreased in -CD solution, asymptotically to a value of V_a in CD-free water. The dependence of V_a on C_a provided the binding constant (K) of 1:1 complex, the volume change in complex formation, and the partial molar volume of complex itself. The complex formation mechanism has been discussed on the basis of these values and their carbon number dependences in the respect of geometric behavior, hydrophobic interaction, and van der Waals interaction. It is concluded that the CD cavity in water is not rigid but flexible for fitting in nicely with guest molecule.     

Inclusion complex of (−)-linalool and β-cyclodextrin

(?)-Linalool is a monoterpene alcohol which is present in the essential oils of several aromatic plants. Recent studies suggest that (?)-linalool has antimicrobial, anti-inflammatory, anticancer, antioxidant, and antinociceptive properties in different animal models. The aim of this study was to prepare and characterize inclusion complexes of (?)-linalool with β-cyclodextrin (β-CD). Equimolar binary (?)-linalool/β-CD systems were prepared by physical mixture, paste (PM), and slurry methods (SC) and characterized by differential scanning calorimetry, thermogravimetric analysis, FT-IR spectroscopy, X-ray diffractometry, Karl Fisher titration, and scanning electron microscopy. Thermal characterization indicates the occurrence of complexation, mainly in paste complexes, which is present in the interval from 140 to 280 °C a gradual mass loss (4.6 %), probably related to (?)-linalool loss. FT-IR spectra showed changes that may be related to the formation of intermolecular hydrogen bonds between (?)-linalool and β-CD. The new solid-phase formed using the PM and SC methods, had a crystal structure which was different from the original morphology of β-CD.     

A study of the physicochemical properties and structure of moxifloxacin complex with methyl-β-cyclodextrin

The physicochemical properties and structure of moxifloxacin?methyl-β-cyclodextrin complex have been studied by UV spectroscopy, FTIR spectroscopy, and computer simulation. The optimal conditions for the formation of the complex have been determined, and the dissociation constant of the complex in acidic media (K _dis = (5.0 ± 0.3) × 10^–5 М) has been obtained. It has been found that complexation significantly slows down the release of the drug in acidic media. Experimental results are in good agreement with computer simulation data. The following mechanism of complex formation has been proposed: the incorporation of the aromatic fragment of moxifloxacin into the cavity of methyl-β-cyclodextrin is followed by additional stabilization of the complex via multiple hydrophobic interactions and hydrogen bonding.     

pH-dependent complex formation of amino acids with β-cyclodextrin and quaternary ammonium β-cyclodextrin

Stability constants for the complexes of anionic, neutral (zwitterionic) and protonated forms of l- and d-enantiomers of eight amino acids with β-cyclodextrin and the positively charged quaternary ammonium β-cyclodextrin (QA-β-CD, DS?=?3.6?±?0.3) have been determined by spectrophotometric and pH-potentiometric methods. The highest stability constants have been obtained for the aromatic amino acids phenylalanine, tyrosine and tryptophan. Except the dianion of tyrosine and QA-β-CD, values for the anions in the range of 80–120 have been found, the stability constants for the zwitterionic forms are much smaller and complex formation is negligible with the protonated species. In the case of the other amino acids the differences are less pronounced. The results are interpreted in terms of hydrogen bonding, steric effects and electrostatic interactions between the amino acid moiety and the rims of the cyclodextrins, in addition to the inclusion of the side chain, and are supported by ¹H and ¹³C NMR investigations on the systems containing l-phenylalanine and l-tyrosine. The differences between the complex formation constants of the l- and d-enantiomers do not exceed the limits of experimental error in most cases.     

Study of inclusion complex of β-cyclodextrin and diphenylamine: photophysical and electrochemical behaviors

The photophysical, electrochemical and photoprototropic behaviors of diphenylamine (DPA) in aqueous β-cyclodextrin (β-CD) solution have been investigated using absorption spectroscopy and cyclic voltammetric techniques. Absorption of the neutral and cationic form of DPA is enhanced due to the formation of a 1:1 complex with β-CD. The formation of this complex has been confirmed by Benesi-Hildebrand plot and docking studies by RasMol tool methods. The solid complex of β-CD with DPA is investigated by FT-IR, XRD and AFM methods. The thermodynamic parameters (ΔG, ΔH and ΔS) of inclusion process are also determined. The pK(a) values of neutral-monocation equilibria have been determined with absorption (conjugate acid-base) titrations. A mechanism is proposed to explain the inclusion process.     

Theoretical investigation to characterize the inclusion complex of α-lipoic acid and β-cyclodextrin

We simulated the docking of α-lipoic acid (α-LA) in β-cyclodextrin (β-CD) using two models. We considered in this study complexes formed by 1:1 host–guest stoichiometry in vacuo and in aqueous phase, using PM6, DFT and ONIOM2 hybrid calculations. The results obtained with PM6 method clearly indicate that the complexes formed are energetically favored with or without solvent, model 2 (α-LA entering the cavity of β-CD from its wide side by COOH group) is found more favored than model 1 (α-LA entering into the cavity of β-CD from its wide side by cyclic group), the preference being greater in the case of ONIOM2 calculations. In addition, NBO analysis gives that mutual interactions between the donor and acceptor orbitals of α-lipoic acid and β-CD plays an important role to the stabilization of such a complex. Finally, ¹H nuclear magnetic resonance (NMR) chemical shifts of free and complexed α-LA were calculated by the Gauge-Including Atomic Orbital (GIAO) method and compared with available experimental data. The results of GIAO calculations were analyzed and discussed.     

A comparative study of vibrational dynamics of α- and β-forms of poly(β-hydroxybutyrate)

Normal modes and their dispersion are obtained for planar zig-zag form of poly(β-hydroxybutyrate) using Urey-Bradley force field. A comparison is made with the spectra of its helical form. Apart from detailed assignment of modes, various characteristic features of dispersion curves have been explained as arising due to internal symmetry in energy momentum space. The density-of-states have been used to calculate heat capacity in the temperature range 10-450 K using Debye's formalism.     

Structure of guest-host complexes of β-cyclodextrin with arenes: a quantum-chemical study

The structure of β-cyclodextrin (β-CD), as well as the structure and energetics of β-CD-naphthalene, β-CD-fluorene, β-CD-phenanthrene, β-CD-cyclohexane (1:1), and β-CD-naphthalene (2:2) inclusion complexes was studied by the semiempirical MNDO/PM3 method. Calculations of a β-CD-naphthalene-cyclohexane (1:1:1) complex were also performed. The minimum heat of formation was found for the symmetric β-CD conformation withC ₇ symmetry axis. The structure is stabilized by the ring of interunit H-bonds formed by the protons of the 2-OH groups and the O atoms of the 3′-OH groups of the glucose units. Preferableness of this orientation of interunit H-bonds was confirmed byab initio calculations of the molecule of α-(1–4)-glucobiose (maltose) in the MP2/6-31G(d,p)//6-31G(d,p) approximation. The formation of any inclusion compounds of β-CD with arenes is energetically favorable: the complexation energy varies in the range −9 to −12 kcal mol⁻¹. Among complexes with naphthalene, that of composition 2:2 is the most energetically favorable, which is in agreement with experimental data. In this complex, β-CD exists as a dimer of the “head-to-head” type, in which both partners are linked by a system of H-bonds. The structure of the “head-to-head” dimer of β-CD was simulated byab initio calculations of the H-bonded dimer of α-d-glucose in the RHF/6-31G(d,p) approximation. In the dimer, both components are linked by a pair of H-bonds formed by the protons of the 3-OH groups and the O atoms of the, 2-OH groups. The dimerization energies obtained fromab initio and semiempirical MNDO/PM3 and AM1 calculations differ by about 2.5 times (8.6vs 3.2 and 3.8 kcal mol⁻¹, respectively).     

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.