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.     

Interaction of naproxen with β-cyclodextrin and its derivatives/polymer: experimental and molecular modeling studies

The interaction of naproxen with β-cyclodextrin and its derivatives (hosts) as well as polymer has been studied using UV Visible (UV–Vis), Fourier Transform Infrared (FTIR), Nuclear Magnetic Resonance (NMR) spectroscopy and Scanning electron microscopy (SEM). In this paper, the solid inclusion complexes were prepared by freeze drying method. The formation constants of the complexes were determined by UV–Vis method. The adsorption properties of naproxen with β-Cyclodextrin bonded silica stationary phase (CDS) were studied for an in-depth understanding of the host–guest interaction. The inclusion process involving naproxen and hosts was investigated by using the PM3 quantum–mechanical semiempirical method. The stabilization energy values obtained from the semiempirical calculation showed the same relation with the formation constant values determined by UV–Vis spectroscopy.     

Reactions of cyclopentanone, γ-butyrolactone,and their derivatives with α-hydroxyethyl radicals

The interaction of cyclopentanone, 2-cyclopentenone, 1,3-cyclopentanedione, 3-methyl-1,2-cyclopentanedione, γ-butyrolactone, 2(5H)-furanone, ascorbic acid, and 5,6-O-isopropylidenyl-2,3-O-dimethylascorbic acid with α-hydroxyethyl radicals (α-HER) generated during the radiolysis of deaerated ethanol has been studied in the continuous irradiation mode. The test compounds, except γ-butyrolactone, oxidize α-HER. 2(5H)-Furanone and 2-cyclopentenone give hydroxyethylation products via the free-radical chain mechanism. In contrast to 2(5H)-furanone and 2-cyclopentenone, ascorbic and 5,6-O-isopropylidenyl-2,3-O-dimethyl-L-ascorbic acids are weaker oxidants for α-HER and attach these radicals at the multiple carbon-carbon bonds.     

Long-lived phosphorescence of aqueous solutions of β-cyclodextrin complexes with naphthalene and its derivatives at room temperature

A long-lived phosphorescence at room temperature (lifetime>1 s) of aqueous solutions of β-cyclodextrin complexes with naphthalene and its derivatives was found. The phosphorescence isobserved for aggregated complexes that form in water a light-scattering suspension, and its low intensity is due to predomination of 2∶2 complexes with efficient excimer fluorescence. Complexes containing isolated aromatic molecules are assumed to be the centers of fluorescence. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2022–2024, October, 1999.     

Synthesis of conjugates of β-cyclodextrin with polyamidoamine dendrimers and their molecular inclusion interaction with levofloxacin lactate

Polyamidoamine (PAMAM) dendrimers of different generations (G2 and G4) conjugated with β-cyclodextrin (β-CD), PAMAM (G2, G4)-CD, were synthesized using substitution reaction from mono-6-iodine-β-cyclodextrin and PAMAM dendrimers. The resulting molecular structures were characterized by NMR, IR. The molecular interaction between various dendrimers and levofloxacin lactate (LFL) were investigated by monitoring the fluorescence of LFL in the presence of dendrimers in buffer solution (pH 7.4) at 25?°C. It was found that the PAMAM (G2, G4)-CD possesses higher sensitizing ability than that of the corresponding parent dendrimers and natural β-CD, and increases concomitantly with the increases of generation and content of β-CD, suggesting that the PAMAM (G2, G4)-CD possesses stronger inclusion ability with LFL. The possible interaction mechanism between PAMAM-CD and LFL was proposed by ¹H NMR analysis and theoretical calculation. The results show that the LFL molecule is located at the amine end of dendrimer molecule and along the side of cyclodextrin cavities to form supramolecular complexes. Furthermore, results indicate that the main driving force of the complex could be attributed to the electrostatic interactions and hydrogen bonding between LFL and PAMAM-CD, as well as the synergistic effect of intermolecular forces.     

The Interactions of Titanocene Dihalides with α-, β- and γ-cyclodextrin Host Molecules

The inclusion of titanocene dihalides (X = F, Cl) into -, - and -cyclodextrin hosts was studied by NMR spectroscopy, thermal analysis and mass spectrometry. It was found that -cyclodextrin does not form inclusion complexes with titanocene halides whereas - and -cyclodextrin do form such complexes. According to the changes in NMR spectra we propose that there is a shallow penetration of a guest molecule of titanocene dihalide into the cavity in the case of -cyclodextrin, but deeper penetration in the case of -cyclodextrin. The stability of the latter inclusion complexes was studied by NMR shift titration.     

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.     

Mandelic acid catalyzed one-pot three-component synthesis of α-aminonitriles and α-aminophosphonates under solvent-free conditions at room temperature

Abstract

A simple, mild, straightforward, efficient and eco-friendly protocol has been developed for the synthesis of a series of α-aminonitriles via the one-pot three-component Strecker reactions between various aldehydes, amines and trimethylsilyl cyanide using a catalytic amount of mandelic acid as a naturally occurring, low-cost, efficient organo-catalyst under solvent-free conditions at room temperature. Under the same optimized conditions synthesis of α-aminophosphonates were also achieved via the one-pot three-component Kabachnik-Fields reactions of aldehydes, amines and triethyl phosphate.     

Combined computational and experimental study on the inclusion complexes of β-cyclodextrin with selected food phenolic compounds

Phenolic compounds, such as caffeic acid, trans-ferulic, acid and p-coumaric acid that are commonly found in food products, are beneficial for human health. Cyclodextrins can form inclusion complexes with various organic compounds in which the physiochemical properties of the included organic molecules are changed. In this study, inclusion complexes of three phenolic compounds with β-cyclodextrin were investigated. The complexes were characterized by various analytical methods, including nuclear magnetic resonance (NMR) spectroscopy, Fourier IR (FT-IR) spectroscopy, mass spectrometry, differential scanning calorimetry, and scanning electron microscopy. Results showed that the phenolic compounds used in this study were able to form inclusion complexes in the hydrophobic cavity of β-cyclodextrin by non-covalent bonds. Their physicochemical properties were changed due to the complex formation. In addition, a computational study was performed to find factors that were responsible for binding forces between flavors and β-cyclodextrin. The quantum-mechanical calculations supported the results obtained from experimental studies. Thus, ΔH_f for the complex of p-coumaric acid and β-cyclodextrin has been found as ??11.72 kcal/mol, which was about 3 kcal/mol more stable than for inclusion complexes of other flavors. Energies of frontier orbitals (higher occupied molecular orbital (HOMO) and lower unoccupied molecular orbital (LUMO)) were analyzed, and it was found that H-L gap for the complex of p-coumaric acid and β-cyclodextrin had the largest value (8.19 eV) in comparison to other complexes, which confirmed the experimental findings of the most stabile complex.

     

Spectrofluorometric, thermal, and molecular mechanics studies of the inclusion complexation of selected imidazoline-derived drugs with β-cyclodextrin in aqueous media

The inclusion complexes of selected imidazoline-derived drugs, namely Antazoline (AN), Naphazoline (NP) and Xylometazoline (XM) with β-cyclodextrin (β-CD) were investigated using steady-state fluorescence spectroscopy, differential scanning calorimetry (DSC), and molecular mechanics (MM) calculations and modeling. The modified form of the Benesi-Hildebrand relation was employed for estimating the formation constant (K_f) of the 1:1 inclusion complexes, which was applied based on measuring the variation in the fluorescence intensity of the guest molecule as a function of growing β-CD concentration. On the other hand, the formation of the inclusion complexes was verified by analyzing solid samples of the complexes using DSC. The thermodynamics of the inclusion complexation, standard enthalpy (ΔH°) and entropy changes −(ΔS°) were obtained from the temperature-dependence of K_f. Obtained values of ΔH° and ΔS° indicated that the inclusion process favorably proceeds through enthalpy changes that was sufficiently predominant to compensate for the unfavorable entropy changes. MM calculations revealed that the proposed drugs molecules can form 1:1 inclusion complexes with β-CD that are stabilized predominantly through van der Waals forces. In addition, MM calculation provided the energetically favored configuration of the inclusion complexes, where NP and XM can be included inside the β-CD cavity through its wide rim, whereas AN can penetrate through the narrow rim of the β-CD cavity.     

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.     

Inclusion complexation of chloropropham with β-cyclodextrin: preparation, characterization and molecular modeling

An inclusion complex between the agrochemical chloropropham (CIPC) and β-cyclodextrin (β-CD) was prepared. A 2:1 host-guest stoichiometry was conformed by elemental analysis. From the phase solubility studies, the calculated stepwise stability constants were K(1)=224.6L/mol and K(2)=939.2L/mol, respectively. FT-IR, thermoanalysis and (1)H NMR spectra were applied to characterize the complex. It was speculated that the inclusion mode was two β-CD cavities included the chlorophenyl and the isopropyl moiety of one CIPC molecule, which was in agreement with the most predominant configuration optimized by molecular modeling. By complexation with β-CD, the water solubility and the thermal stability of CIPC were prominently improved.     

Effect of β-cyclodextrin and its derivatives on caveolae disruption, relationships with their cholesterol extraction capacities

Endothelial cells (HUVEC) were treated with β-cyclodextrin (β-CD) and hydroxypropylated or methylated derivatives solutions to confirm their lack of affinity with phospholipids and their specificity towards cholesterol. Further studies were performed on bovine aortic endothelial cells to assess the effect of β-CDs (mainly methylated derivatives) on membrane microdomains (lipid rafts or caveolae), by detecting the caveolae marker caveolin-1 in fractions of sucrose gradients. A displacement from the lighter to the heavier fractions, characteristic of caveolae disruption, was observed using CDs. The strongest effect was obtained with dimethyl-β-CD, for which an accumulation of caveolin-1 was observed in the bottom of the gradient. Crysmeb^® and trimethyl-β-CD seemed to have the weaker effects as a significative amount of caveolin-1 was still detected in the light fraction corresponding to caveolae. β-CD and CDs having a degree of methylation a bit lower than 2 showed intermediate effects. The results of the present study on microdomains seem in good correlation with the cell cholesterol extraction capacities of CDs previously determined.     

Interaction of naproxen with α-, β-, and γ-hydroxypropyl cyclodextrins in solution and in the solid state

Solid combinations of naproxen with amorphous hydroxypropyl derivatives of -, -, and -cyclodextrin with an average substitution degree per anhydroglucose unit of 0.6 were investigated for thermal behaviour (differential scanning calorimetry), drug crystallinity (X-ray diffractometry), and dissolution rate (dispersed amount and rotating disc methods). Phase-solubility analysis and computer-aided molecular modelling were carried out to study the inclusion complexation of naproxen with hydroxypropyl cyclodextrins. The cavity size of the host is a selective factor for the solubilizing effect, complexing ability, and dissolution rate enhancement on naproxen, hydroxypropyl -cyclodextrin being markedly the most effective derivative. No relationship was found between the decrease in crystallinity of the drug dispersed in the amorphous carrier matrix and the geometrical features of the cyclodextrin macrocycle.     

Theoretical am1 studies of inclusion complexes of α- and β-cyclodextrins with methylated benzoic acids and phenol,and γ-cyclodextrin with buckminsterfullerene

Semiempirical AM1 calculations have been performed on the inclusion complexes of - and -cyclodextrin with benzoic acid and phenol and -cyclodextrin with methylated benzoic acids in the head first and tail first positions. The results show that -cyclodextrin complexes with phenol and benzoic acid guests in the head first position are more stable than in the tail first position, while -cyclodextrin complexes with the same guests prefer the tail first position. The preferred orientation for -cyclodextrin with methylated benzoic acids is determined by the position of the methyl substituent(s). In general, para-methyl benzoic acid derivatives prefer the tail first position. -cyclodextrin forms a slightly unstable 1:1 complex with C₆₀ (3.4 kcal/mol), but two -cyclodextrins provide enough stabilization by about 10 kcal/mol to cage-in the C₆₀.     

One-pot synthesis of methyl piperazinyl–quinolinyl nicotinonitrile derivatives under microwave conditions and molecular docking studies with DNA

Derivatives of methyl piperazinyl–quinolinyl nicotinonitrile were synthesised by one-pot method under microwave conditions. This was achieved using the Knoevenagel condensation reaction. The novel derivatives described above were purified by column chromatography and characterised by FT-IR, ¹H, ¹³C, 2D-NMR and HRMS spectroscopic techniques. Furthermore, molecular docking was used to determine the binding sites of DNA with selected compounds. The synthetic method developed in this study showed several advantages including simplicity, high yield of products, coupled with safety and a short reaction time of 15 min.     

Reaction of aspartic acid derivatives with Grignard reagents—synthesis of γ,γ-disubstituted α- and β-amino-butyrolactones

A series of γ,γ-dimethyl and γ,γ-diphenyl substituted α- and β-amino-butyrolactones have been prepared in enantiomerically pure form using l-aspartic acid as a chiral building block. For the final Grignard reaction the difference in chemical reactivity between the carboxyl groups of aspartic acid was increased or inverted by preparing the corresponding semiesters, diesters and anhydrides. The resulting hydroxyacids and hydroxyesters lactonised in most cases during work up. Thus, (2S)-2-ethoxycarbonylamino-succinic acid-4-methylester 1 reacted with methylmagnesium iodide to form (3S)-3-ethoxycarbonylamino-5,5-dimethyl-tetrahydrofuran-2-one 2b. Two interesting side products were obtained and were found to result from attack at the C-1 carboxylic acid rather than the C-4 carboxylic ester group leading to (3S)-3-ethoxycarbonylamino-4-oxo-pentanoic acid methylester 3 and (4S)-4-ethoxycarbonylamino-5,5-dimethyl-tetrahydrofuran-2-one 5a.     

Electrophoretic mobility of ester betulin derivatives and their complexation with γ-cyclodextrin studied by capillary electrophoresis in aqueous solutions at different pH values

In this article, capillary electrophoresis was used to measure the effective electrophoretic mobility of ester betulin derivatives as a pH function and to study their complexation with γ-cyclodextrin (γ-CD). The electrophoretic mobility of betulin 3,28-diphthalate (DPhB) and 3,28-disuccinate (DScB) changed unusually with decreasing pH: instead of decreasing, it first increased and then decreased. This fact as well as the turbidity of sample solutions at pH from 2.5 to 6, broadening of electrophoretic peaks and a decrease in the surface tension of the solutions indicates that these betulin derivatives, being amphiphilic compounds and weak acids, exist as micelles in aqueous solutions at pH 6 and below. The inclusion complexation of betulin derivatives with γ-CD at pH 9.18 and 4.5 was studied by mobility shift affinity capillary electrophoresis. At pH 9.18, the apparent binding (stability) constant logarithms for 1:1 γ-CD complexes of DPhB, betulin 3,28-disulfate (DSB) and DScB with 95% confidence interval limits were equal to 7.44 ± 0.02, 7.09 (7.01–7.19), and 6.97 (6.87–7.08) at 25°C, respectively. At pH 4.5, the binding constant for the DSB complex was slightly lower, while the micelle formation did not allow determining the exact values of the constants for the DPhB and DScB complexes.     

PPh3-catalyzed Mannich reaction: a facile one-pot synthesis of β-amino carbonyl compounds under solvent-free conditions at room temperature

Research on Chemical Intermediates - PPh3 was used as an efficient catalyst for the one-pot three-component Mannich reactions of acetophenone with different aromatic amines and aromatic aldehydes...     

Nano titania-supported sulfonic acid catalyzed synthesis of α,α′-bis(substituted-benzylidene)cycloalkanones and of their xanthene derivatives under solvent-free conditions

An efficient, rapid and green synthesis of α,α′-bis(substituted-benzylidene)cycloalkanones and their xanthene derivatives is reported under solvent-free conditions using nano titania-supported sulfonic acid (n-TSA) as a reusable catalyst. This method offers many advantages, such as environmental friendliness reaction conditions, simplicity, short reaction times, easy work-up, reusability of catalyst, and high yields of products. Eight new compounds are reported too.