Synthesis and Characterization of Polymer Brushes Containing β-Cyclodextrin Grafted to Magnetic Nanoparticles for Determination of Naproxen in Urine

β-Cyclodextrin containing polymer brushes were grafted to magnetic nanoparticles following free radical copolymerization of N,N-dimethylacrylamide and allyl glycidyl ether on the surface. The products were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, elemental analysis, and transmission electron microscopy and employed for solid phase extraction of naproxen in human urine. The profile of the naproxen adsorbed by the nanoparticles demonstrated high accessibility of the β-cyclodextrin. Scatchard analysis indicated that the capacity of the nanoparticles was 112 µmol g^?1 at 25°C and a pH of 5. The adsorption data of naproxen were considered by Langmuir, Freundlich, Redlich–Peterson, and Temkin isotherms. Approximately 55% of naproxen was released in simulated gastric fluid in 30 min and 94% in simulated intestinal fluid in 30 h. These data have indicated the utility of the naproxen loaded- β-cyclodextrin containing polymer brushes grafted to magnetic nanoparticles for enteric drug delivery.     

Synthesis and Adsorption Property of Dihydroxyl Azacrown Ether—Grafted Chitosan

A novel dihydroxyl azacrown ether chitosan was synthesized by reacting dihydroxyl azacrown ether with epoxy activated chitosan. The adsorption property of the azacrown ether chitosan for Pb^2 , Cr^3 , and Ag^ , were determined. The experimental results showed that the dihydroxyl azacrown ether grafted chitosan has high adsorption capacity and high selectivity for some metal ions.     

Association Constant Prediction for the Inclusion of α-Cyclodextrin with Benzene Derivatives by an Artificial Neural Network

The association constants (K_a) for the inclusion complexation of -cyclodextrin (-CD) with 72 mono- and 1,4-disubstituted benzenes were predicted successfully by an artificial neural network (ANN) with molar refraction (R_m) and hydrophobic constant () as input parameters, which reflect the volume and hydrophobicity of the substituents respectively. The predictions strongly suggested that the inclusion complexation of -CD with guest molecules was mainly driven by van der Waals forces and hydrophobic interactions     

Spectral Differences of the Molecule-ion Adducts of β-Cyclodextrin and Lithium Carbonate

A small shielding effect on the hydrogen atoms of chiral carbons of β-cyclodextrin (β-CD) was detected by ¹H nuclear magnetic resonance, but a large environmental change of the chiral carbon atoms at high concentration ratios of lithium carbonate (Li₂CO₃) to β-CD was observed by polarimetry in aqueous solution. These findings urged us to investigate whether different formation conditions of the molecule-ion system between Li₂CO₃ and β-CD in solid state were involved in different spectral performances. To answer the question, we prepared three adducts of Li₂CO₃ to β-CD, i.e., samples 1, 2, and 3, by magnetic stirring, solvothermal and grinding conditions, respectively. Powder X-ray diffraction and Fourier transformation infrared spectroscopy provided the information of formation of the three molecule-ion adducts. Besides, scanning electron microscope images provided different surface information of the three adducts. Further, significant spectral differences in thermal behavior of these adducts were found by thermogravimetry and derivative thermogravimetry.     

Theoretical Study on the Inclusion Complex of β-Cyclodextrin and Nitrobenzene

Quantum chemical calculations were carried out to investigate the structures and properties for the inclusion complexes of nitrobenzene (NB) into β-cyclodextrin. Two low-energy conformations of β-cyclodextrin (A and B) in the gas phase were initially investigated by the PM3 and B3LYP/6-31+G(d,p) calculations, respectively. Three different orientations were considered in the inclusion process of A and B with NB to form 1:1 complexes. Potential energy scan by PM3 calculations indicated that the phenyl orientation Ab for conformation A and the equator orientation Bc for conformation B are more favorable in energy, respectively. We also considered the 2:1 inclusion complexes of host A or B with guest NB in the gas phase. PM3 calculation indicated that the host-guest interaction energies to form 1:1 complexes are more negative than those to form 2:1 NB/B complexes. Finally, we studied the solvent effect of NB/CD complex, and PM3 results show that the influence of water molecules on the inclusion process is very important. The driving forces for the inclusion process and the geometries of complexes were discussed in detail.     

Spectroscopic Study of the Interactions of Buflomedil to Serum Albumin and β-Cyclodextrin

The effects of buflomedil (BFM), a novel cerebrovascular medicine, on serum albumin and the feasibility of ??-cyclodextrin (??-CD) acting as a controlled releaser for BFM were investigated by molecular spectroscopy methods, including fluorescence emission, UV?Cvisible absorption, Fourier transform infrared (FT-IR), synchronous and three-dimensional fluorescence spectroscopies. The interaction of BFM with bovine serum albumin (BSA) was analyzed by fluorescence quenching and it was found that BFM had reacted with BSA in the ground state and had affected the secondary structure of BSA. The observed binding constant K _b, the number of binding sites n, the distance r between donor (BSA) and acceptor (BFM), the enthalpy change (??H ^?? ), Gibbs energy change (??G ^?? ) and entropy change (??S ^?? ) at different temperatures were calculated. The inclusion reaction between ??-CD and BFM was explored by the Lineweaver?CBurk equation. The inclusion constants and the thermodynamic parameters were determined. The mechanism of the inclusion reaction was discussed and the controlled release characteristics of ??-CD to BFM were considered at the molecule level.     

Derivatives Of α-Cyclodextrin and the Synthesis of 6-O-α-D-Glucopyranosyl-α-Cyclodextrin

Abstract

Regioselective silylation of α-cyclodextrin with tert-butyl-dimethylsilyl chloride in N, N-dimethylformamide in the presence of imidazole gave, in 75% yield, the hexakis(6-O-tert-butyldimethylsilyl) derivative 2, which was transformed into the hexakis(2,3-di-O-methyl, 6-O-methyl, 2,3-di-O-propyl, and 2,3-di-O-acetyl) derivatives. On methanesulfonylation and p-toluenesulfonylation, the hexakis(2,3-di-O-acetyl) derivative 16 afforded the hexakis(2,3-di-O-acetyl-6-O-methylsulfonyl 17 and 2,3-di-O-acetyl-6-O-p -tolylsulfonyl 18) derivatives, respectively. Nucleophilic displacement of 17 and 18 with iodide, bromide, chloride, and azide ions afforded the hexakis(6-deoxy-6-iodo 19, 6-bromo-6-deoxy, 6-chloro-6-deoxy, and 6-azido-6-deoxy) derivatives, respectively, of α-cyclodextrin dodeca-acetate. The hexakis (2, 3-di-O-acetyl-6-deoxy) derivative was prepared from 19. Selective glucosylation of 16 with 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl bromide under catalysis by halide ion, followed by removal of protecting groups, furnished 6-O-α-D-glucopyranosyl-α-cyclodextrin.     

Study of the Podophyllotoxin β-Cyclodextrin Inclusion Complex

The structure of the podophyllotoxin (P)/-cyclodextrin(-CD) inclusion complexhas been studied by infrared spectroscopy, UVspectroscopy, NMR spectroscopy and X-raydiffractometry. The association constant is 128 M^-1in water, calculated from thestraight portion of the phase-solubility diagram.     

Cucurbituril and β-Cyclodextrin as Hosts for the Complexation of Organic Dyes

The complexation of neutral organic molecules by cucurbituril and-cyclodextrin in formic acid was studied by means ofspectrophotometric titrations. In the case of -cyclodextrin thecomposition of the solvent has almost no influence upon the stability of thecomplexes formed. This situation is completely different for cucurbituril.Due to its interactions with protons the measured stability constants of thecomplexes formed with organic molecules increase with decreasing acidconcentration. At low acid concentrations cucurbituril forms more stablecomplexes with organic molecules than -cyclodextrin.     

Inclusion Complexation of Carbaryl and β-Cyclodextrin in Solution and in the Solid State

This study was carried out with the aim ofinvestigating the interactions between-cyclodextrin and carbaryl, a carbamatepesticide, and their effect on some physico-chemicalproperties of carbaryl, such as aqueous solubility andlipophilicity. The interactions between carbaryl and-cyclodextrin were thoroughly investigated bothin solution and in the solid state. The effect of-cyclodextrin on the aqueous solubility ofcarbaryl was evaluated by the phase solubility method.The amount of carbaryl dissolved increased linearlywith the addition of -cyclodextrin according toan A_L type plot and without precipitation of thecomplex. The apparent stability constant of thecomplex was 289 ± 21 M^-1, assuming a 1 : 1stoichiometry; this value was confirmed by a methodbased on circular dichroism measurements.Equimolar carbaryl/-cyclodextrin solid systemswere prepared by physical-mixing and freeze-drying,and fully characterised by Differential ScanningCalorimetry, X-ray powder diffractometry and FourierTransform Infra-Red analysis. The results of the solidstate study demonstrated that the freeze-drying methodyields a system with a high degree of amorphisationand yields an inclusion complex.The dissolution profile of the pesticide was affectedby the physico-chemical properties of each solidsystem, the freeze-dried form dissolving more rapidly. However, the physical association of-cyclodextrin and carbaryl enhanced the aqueoussolubility of the insecticide as well.     

NMR Spectral Assignment of Per-substituted Key-Intermediates of β-Cyclodextrin and Implications in the Structures of the Derivatives

The compounds, 6-per-O-(t-butyldimethylsilyl)--cyclodextrin(1), 2,3-per-O-benzyl-6-per-O-(t-butyldimethylsilyl)--cyclodextrin(2), 2,3-per-O-benzyl--cyclodextrin (3),2,3,6-per-O-benzyl--cyclodextrin (4),2,3,6-per-O-benzoyl--cyclodextrin (5), are used as keyintermediates in the synthesis of selectively substituted -CD derivatives. Simple and assignable ¹H and ¹³C NMR spectra (chemical shifts and coupling constants) were obtained for compounds1–4 indicating C₇ symmetry, ⁴C₁ glucose conformation and major arrangement of H6, H6' atoms at the primary side. The derivative 5, however, gave very broad peaksat room temperature. The peaks could partially be assigned at 270 K, but the broadening was still present at 220 K. This implies that there exist several conformers of similar energyand C₁ symmetry that continuously interchange, since there is not a single type of stabilizing interaction thatpredominates. We attributed this phenomenon to the presence of the carbonyl group, which probablydisfavors - stacking and induces random arrangements of the aromatic rings.     

Study of the Supramolecular Inclusion of β-Cyclodextrin with Andrographolide

An inclusion complex of -cyclodextrin with andrographolide (Andro) was prepared by using a convenient new method of microwave irradiation. The structure of the inclusion complex was determined by UV and IR analyses as well as ¹H NMR, ¹³C NMR and two dimensional NOE spectroscopic measurements. The results indicated that the possible stoichiometry of complex formation is 1:1 (guest:host ratio) and the two isomeric 1:1 inclusion complexes are present simultaneously in solution. Thermal studies proved the thermal stability of the inclusion complex.     

Regioselective Acetylation of β-Cyclodextrin

One-stage methods of synthesis of water-soluble -cyclodextrins selectively acetylated by primary or secondary hydroxy groups have been found, that make use of acetyl chloride and hydrogen chloride acceptors of different nature.     

Exciton Coupling and Complexation Behaviour of β-Cyclodextrin Naphthoate

The host–guest complexation behaviour of-cyclodextrin 6-O-mono-2-naphthoate(1) and 6-[(N-2-naphthoyl-2-aminoethyl) amino]-6-deoxy--cyclodextrin (2) have been studied by the circular dichroism method. The exciton coupling band of 1 suggests that two naphthoyl moieties are partly included in one -CD cavity. Host 1 could form a dimer in a more polar solvent and the dimer could be dissociated in a less polar solvent or by adding a guest. Solvent-induced, concentrationinduced, and guest-induced circular dichroism variations were examined. No exciton coupling was observed for host 2.     

Synthetic and Conformational Studies of Bridged β-Cyclodextrin Dimers

Cyclodextrins (CD) have been found wide applications in the artificial enzymes^[1] due to their ability of recognizing and binding a variety of organic and inorganic substrates in aqueous solution. In some cases, however, their binding capacity and selectivity are not good enough to make them useful (K_a~10²-10⁴L/mol). Breslow et.al^[2,3] have reported that the bridged cyclodextrin dimers can complex some kinds of substrates strongly (K_a~10⁶-10¹¹L/mol) because of their more recognition sites. Recently, we synthesized a series of bridged β-CD dimers. It has been observed that the conformation of the dimers changed markedly upon the solvents.     

Direct and Regioselective Di-α-fucosylation on the Secondary Rim of β-Cyclodextrin

A straightforward glycosylation method is described to regio- and stereoselectively introduce two α-l -fucose moieties directly to the secondary rim of β-cyclodextrin. Using NMR and MS fragmentation studies, the nonasaccharide structure was determined, which was also visualized using molecular dynamics simulations. The reported glycosylation method proved to be robust on gram-scale, and may be generally applied to directly glycosylate β-cyclodextrins to make well-defined multivalent glycoclusters.     

Changes in the Solubility of β-Cyclodextrin on Complex Formation: Guest Enforced Solubility of β-Cyclodextrin Inclusion Complexes

The most common native host molecule, -cyclodextrin (cycloheptaamylose) is able toform inclusion complexes with a large variety of guestmolecules (or ions) of different size and shape. Theproperties of the included guest molecule are highlyinfluenced by the host-guest interaction, and thepractical usefulness of -cyclodextrin isdependent on these effects. These changes are mainlyinvestigated from the point of view of the guest andto a lesser extent from that of the host. In spite ofthis, the kind of guests and that of the host-guestinteractions during the formation of the inclusioncomplex seem to influence the properties of thehydrophilic domain of -cyclodextrin (i.e. thatof the supramolecule itself), too, and this effect canbe well demonstrated by the change of solubility ofdifferent -cyclodextrin inclusion complexes.This change can be best correlated with the solubilityof the guest as if the guest enforced its solubilityon the supramolecule.     

Determination of the equilibrium melting point of the β-form of polypropylene

The melting behavior of the -form of isotactic polypropylene (-iPP) was investigated as a function of crystallization time and temperature. Calcium suberate, a selective -nucleating agent was used to produce samples that consist entirely of -form i-PP. The experimental melting points were recorded at different crystallization times and were extrapolated to the start of the crystallization process in order to eliminate the effect of lamellar thickening. Using the non-linear Hoffman—Weeks approach to correlate these extrapolated experimental melting temperatures with the corresponding crystallization temperatures, an equilibrium melting point of 209°C was obtained for -iPP. The equilibrium melting point estimated through the non-linear Hoffman—Weeks analysis is about 30°C higher than that (T _m ⁰=177°C) obtained on the basis of the linear extrapolation. These results are consistent with earlier claims that a linear extrapolation of T _m–T _c data leads to an underestimation of the equilibrium melting point. The results obtained for -iPP exemplify the importance of accounting for both the isothermal lamellar thickening effects and the non-linearity in the T _m–T _c correlation, when the determination of an equilibrium melting point is carried out using a procedure based on the predictions of the Lauritzen—Hoffman secondary nucleation theory.This revised version was published online in November 2005 with corrections to the Cover Date.     

The Preparation and Properties of Thermosensitive Hydrogels Based on Chitosan Grafted N-isopropylacrylamide via γ-Radiation

Thermosensitivehydrogels. were prepared by graft polymerization of chitosan and N-isopropylacrylamide via ^60Co γ-radiation.The effects of monomer concentration and total irradiation dose on percent grafting and grafting efficiency were studied.The thermosensitivity and swelling properties of the hydrogels were investigated.