Study of chemical processes in the modification of epoxide polymers by aluminum oxide

The processes occurring during the modification of epoxy polymers by various polymorphic aluminum oxide modifications (γ-AlO(OH), γ-Al₂O₃, α-Al₂O₃) with epoxy groups were studied by the methods of IR Fourier spectroscopy, chemical analysis, and differential scanning calorimetry (DSC) by an example of a model compound (phenyl glycidyl ether). Two types of interactions were revealed: a direct chemical reaction of phenyl glycidyl ether with the surface hydroxy groups of alyminum oxide, and phenyl glycidyl ether homopolymerization. By processing by graphical method the data of chemical analysis on the diminishing in amount of epoxy groups in the course of the polycondensation reaction the value of activation energy 106–110 kJ mol⁻¹ of the process of phenyl glycidyl ether interaction with aluminum γ-oxide was determined.     

A Simulation on the Complexation of Cyclodextrins with Phospholipid Headgroups

The inclusion complexes of α-, β- and γ-cyclodextrin (CD) with three isolated phospholipid (PI – phosphatidylinositol; PS – phosphatidylserine; and PE – phosphatidylethanolamine) headgroups were studied using a flexible docking algorithm FDOCK based on molecular mechanics (CFF91 force filed). In the three phospholipid headgroups, PI headgroup exhibits the strongest affinity for CD, and the affinity of PS headgroup is greater than that of PE headgroup. By investigating the energy distribution and the complex structure in the inclusion procedure, it can be found that the van der Waals force is the main driving force responsible for the complexation. For the α-CD complex of PI headgroup, more than one inclusion complex should coexist due to the steric hindrance, which is reasonably consistent with the experimental results. Furthermore, analyses of the complex of PS and PE headgroup with α-CD also show that two or three possible complexes may appear in the inclusion process, and the complex structure with full inclusion is of the lowest energy and should be the most stable structure in the mixture. For β-␣and γ-CD, the energies of the most stable complexes structures for the three phospholipids headgroups were also discussed.     

Effect of cyclodextrins on pH-induced conformational transition of poly(methacrylic acid)

A pH-induced conformational transition of atactic poly(2-methylprop-2-enoic acid) (poly(methacrylic acid), PMMA) from the contracted to expanded conformation was investigated by viscometry, potentiometric titration, and anthracene solubilisation in the presence of low-molecular-mass non-ionogenic co-solutes-glucose, α-cyclodextrin (αCD), and γ-cyclodextrin (γCD), respectively. No effect of glucose and αCD on the conformational transition was observed with either of the methods used. On the other hand, the characteristic features of the conformational transition were absent in the presence of γCD. The different effects of the co-solutes indicate that the interaction between PMAA and γCD corresponds to the partial inclusion of the PMAA chain into the γCD cavity. The viscometry and anthracene solubilisation imply that γCD promotes the expanded conformation of PMAA at low pH. The potentiometric titration does not support this conclusion. Even though there is no break on the Henderson-Hasselbalch plot, a characteristic of the conformational transition, the potentiometric behaviour corresponds to that of the contracted PMMA conformation. Thus the results suggest the hierarchical picture of the PMAA conformation at low pH in which the local arrangement of the PMAA chain is a prerequisite for clustering on a larger scale.     

Inclusion complexes of fusidic acid and three structurally related compounds with cyclodextrins

The inclusion complexes between fusidate, 3-keto fusidate, 11-keto fusidate and 11-deoxy fusidate and α-, β-, and γ-cyclodextrin (CD) were studied using capillary electrophoresis. By monitoring the changes in mobility of the negatively charged compounds in the presence of varying amount of CD the stability constants of the complexes formed could be obtained. In the case of α- and β-CD the obtained results could be modelled to a simple model assuming 1:1 stoichiometry, revealing, not surprisingly, that β-CD formed a stronger complex compared to α-CD. A model assuming 1:2 (fusidate:CD) stoichiometry could be fitted to the data obtained with γ-CD. The results showed that the different fusidanes formed very strong 1:1 complexes with γ-CD as well as a quite weak 1:2 complex. 3-keto-, 11-keto- and 11-deoxy-fusidate formed stronger complexes compared to fusidate, probably due to an decrease in hydrophilicity caused by the reduced number of hydroxyl groups. The complex between γ-CD and fusidate was studied by use of 2D-NMR spectroscopy. The results showed that most of the hydrogen atoms of fusidate show interactions with the hydrogen atoms in the cavity of γ-CD. The interaction pattern suggests that fusidate may be fully embedded in the cavity of γ-CD. No interactions between fusidate and the hydrogen atoms situated at the outside of the CD were found.     

Investigation of Drug Nanoparticle Formation by Co-grinding with Cyclodextrins: Studies for Indomethacin, Furosemide and Naproxen

Drugs with poor water solubility were co-ground with cyclodextrins (CDs) to create nanoparticles with improved solubility characteristics. Indomethacin (IDM), furosemide (FRM) and naproxen (NAP) were co-ground with β-CD at the molar ratio of 2:1 (CD:drug). Co-grinding of a drug with CD resulted in not only the formation of drug nanoparticles but also the solubilization of the drug by inclusion complex formation with CD in aqueous media. The nanoparticle fraction of IDM, and FRM from ground mixtures prepared with β-CD was as high as 60–70% while the solubilization fraction was less than 10%. In contrast, β-CD–NAP ground mixture showed a large fraction, 48%, for drug solubilization and only 4% for nanoparticle formation. Furosemide ground mixtures prepared with α-CD, β-CD and γ-CD showed comparatively high nanoparticle fraction while the solubilization fraction was around 10%. Both the nanoparticle fraction and the solubilization fraction were greater in the IDM–β-CD system than those in γ-CD and α-CD systems. The nanoparticle formation of NAP depended on the types of CD used as a co-grinding additive. Naproxen nanoparticles could be prepared by co-grinding NAP and α-CD, while the solubilization of NAP tended to improve when β-CD or γ-CD was used.     

Thermodynamic evaluation of antibacterial activity for inclusion complexes of amoxicillin with cyclodextrins

The antibacterial action of amoxicillin (AMPC) and the inclusion complexes of AMPC with α-, β- and γ-cyclodextrins (α-CD, β-CD and γ-CD, respectively) to Escherichia coli B (E. coli) was evaluated by isothermal titration microcalorimetry and by petri-dish bioassay method. The effects of the compounds on produced heat during the exponential phase of the E. coli growing were measured and the growing rate constants of the cells was calculated from the power-time (p-t) curve before and after the treatment with AMPC. Results from the both methods showed that the antibacterial activity became stronger in the following order: AMPC-βCD > AMPC-γCD ≈ AMPC-αCD > AMPC only.     

Inclusion complexation of diclofenac with natural and modified cyclodextrins explored through phase solubility, 1H-NMR and molecular modeling studies

Guest–host interactions were examined for neutral diclofenac (Diclo) and Diclofenac sodium (Diclo sodium) with each of the cyclodextrin (CD) derivatives: α-CD, β-CD, γ-CD and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), all in 0.05 M aqueous phosphate buffer solution adjusted to 0.2 M ionic strength with NaCl at 20 °C, and with β-CD at different pHs and temperatures. The pH solubility profiles were measured to obtain the acid–base ionization constants (pK _as) for Diclo in the presence and absence of β-CD. Phase solubility diagrams (PSDs) were also measured and analyzed through rigorous procedures to obtain estimates of the complex formation constants for Diclo/CD and Diclo sodium/CD complexation in aqueous solutions. The results indicate that both Diclo and Diclo sodium form soluble 1:1 complexes with α-, β-, and HP-β-CD. In contrast, Diclo forms soluble 1:1 Diclo/γ-CD complexes, while Diclo sodium forms 1:1 and 2:1 Diclo/γ-CD, but the 1:1 complex saturates at 5.8 mM γ-CD with a solubility product constant (pK _sp = 5.5). Therefore, though overall complex stabilities were found to follow the decreasing order: γ-CD > HP-β-CD > β-CD > α-CD, some complex precipitation problems may be faced with aqueous formulations of Diclo sodium with γ-CD, where the overall concentration of the latter exceeds 5.8 mM γ-CD. Both ¹H-NMR spectroscopic and molecular mechanical modeling (MM⁺) studies of Diclo/β-CD indicate the possible formation of soluble isomeric 1:1 complexes in water.     

Thermal And Structural Characterization of Commercial α-, β-, and γ-Cyclodextrins

α-, β-, and γ-cyclodextrins (CDs) marketed by five different companies were characterized from the thermal and structural point of view. Three αCD samples showed two-step DSC dehydration profiles and their XRD patterns were characteristic for αCD⋅6H₂O form I, whereas one brand with an apparent three-step DSC dehydration behaviour was a mixture of αCD⋅6H₂O form I and anhydrous αCD. The differences in the DSC profiles after dehydration and EGA onset decomposition temperatures recorded for the five βCD brands were attributed to different manufacturing and purification processes. The five γCDs brands showed a common thermal behaviour and very similar XRD patterns. The patterns did not match the idealized pattern of γCD⋅14.1H₂O, indicating the occurrence of two different hydrated crystal structures. This revised version was published online in August 2006 with corrections to the Cover Date.     

Formation of Cyclodextrin Inclusion Complexes with Doxycyclin-Hyclate: NMR Investigation of Their Characterisation and Stability

The solubility of cyclodextrin (CD) can be notably improved when it is included in a polymeric structure. CD was reacted with citric acid, yielding a water-soluble polymer whose inclusion properties towards doxycyclin-hyclate (DOX) as guest molecule were investigated by NMR. The new DOSY (Diffusion Ordered SpectroscopY) method, based on diffusion coefficient measurements is convenient study complexes made of large molecules and it was applied to determine the association constants between DOX and parent β and γ-CD and their polymerised forms. The association constant obtained by DOSY was compared with that determined more classically by the chemical shift variation measurement using Scott's plot.     

Photo-neutron cross-section of 100Mo

The ¹⁰⁰Mo(γ, n) reaction cross-section was experimentally determined at end point bremsstrahlung energy of 10 and 12.5 MeV using off-line γ-ray spectrometric technique. It was also found that ¹⁰⁰Mo(γ, n) reaction cross-section increases sharply from the end point bremsstrahlung energy of 10 MeV to 12.5 MeV, which may be because of GDR around the energy region of 12–16 MeV. The ¹⁰⁰Mo(γ, n) reaction cross-section as a function of photon energy was calculated theoretically using TALYS 1.2 computer code. The flux-weighted average values of ¹⁰⁰Mo(γ, n) reaction cross-section for bremsstrahlung having end point energy of 10 and 12.5 MeV were also calculated using the experimental and theoretical data of mono-energetic photon. The present experimental ¹⁰⁰Mo(γ, n) reaction cross-sections were compared with the bremsstrahlung flux-weighted average values of experimental and theoretical data and found to be in the lower side for 10 MeV and in the higher side for 12.5 MeV.     

List-mode coincidence data analysis for highly selective and low background detection of gamma-nuclides in activated samples

Highly selective and sensitive γ-ray detection was performed by coincidence and anticoincidence event analysis after list-mode data acquisition using an HPGe spectrometer equipped with NaI(Tl) and plastic scintillation detectors. In order to obtain the most suitable detection of specific nuclides, coincidence or anticoincidence spectra could be freely constructed by extracting events with particular time and energy correlations. Although the detector arrangement of this system was the same as that of a typical Compton suppression spectrometer, background counts were drastically reduced and γ-rays of particular nuclides could be selectively detected by using γ-γ, γ-X, γ-X-X, and γ-β⁺ coincidences.     

Application of fast solvent extraction processes to studies of exotic nuclides

The nucleus²³Na has been investigated by studying the primary γ-rays emitted from 53 keV neutron capture in it using a high resolution and high efficiency (100%) HPGe detector and NaI(T1) detector for anti-Compton. 24 primary γ-rays were placed in the²⁴Na, in which 3 primary γ-rays were new ones from a (n, γ) reaction, and reported for the first time. In order to obtain an exact energy calibration within 7 MeV,⁵⁶Fe(n,γ)⁵⁷Fe reaction was used at thermal neutron energy. Intensity calibration was obtained from the²⁷Al(p,γ)²⁸Si reaction atE _p=2046 keV. The neutron binding energy of²⁴Na was determined to be 6959.75 keV.     

Surface characterization of polyimide films

 Various kinds of poly(amide acid)s were prepared by the reaction of four kinds of acid dianhydride and three kinds of diamine in N,N-dimethylacetamide (DMAc). Polyimide films were prepared by casting the poly(amide acid) solution on soda glass substrates, followed by thermal imidization at various temperatures. Contact angles of polyimide films for the sides in contact both with air and with glass substrate (air side and glass side, respectively) were measured to evaluate the dispersive component (γ^D _S) and the nondispersive component (γ^P _S) of surface free energy (γ_S) of polyimide films. It was shown that, for the air side, γ^P _S value decreased greatly and γ^D _S values increased slightly with the development of imidization. Values of γ^P _S for the glass side were much higher than those for the air side. Poly(amide acid) solution was also cast on quartz glass and silicone rubber, and was thermally imidized. The γ^P _S for the quartz glass side was almost the same as that for the soda glass side. But the γ^P _S for the silicone rubber side was as low as the γ^P _S for the air side. Attenuated total reflection infrared spectroscopy of polyimide films showed that the degree of imidization for the glass side surface was not as high as that for the air side surface, and that the amount of polar groups for the glass side surface was higher than that for the air side surface. Among the various kinds of polyimides, there is a slight but clear difference in the values of γ_S and its components, which can be rationalized from the difference in the chemical structure. It was also found that thermal degradation and oxidation can be easily detected from the change of surface free energy and its components for the polyimide films after being treated at high temperatures in both air and vacuo. Received: 22 January 1998 Accepted: 10 March 1998     

Characterization of cyclodextrin glycosyltransferase from Bacillus firmus strain No. 37

The enzyme cyclod extringly cosyltransferase (CGTase), EC2.4.1.19, which produces cyclodextrins (CDs) from starch, was obtained from Bacillus firmus strain no. 37 isolated from Brazilian soil and characterized in the soluble form using as substrate 100 g/L of maltodextrin in 0.05 M Tris-HCl buffer, 5 mM CaCl₂, and appropriate buffers. Enzymatic activity and its activation energy were determined as a function of temperature and pH. The activation energy for the production of β- and γ-CD was 7.5 and 9.9 kcal/mol, respectively. The energy of deactivation was 39 kcal/mol. The enzyme showed little thermal deactivation in the temperature range of 35–60°C, and Arrhenius-type equations were obtained for calculating the activity, deactivation, and half-life as a function of temperature. The molecular weight of the enzyme was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, giving 77.6k Da. Results for CGTase activity as a function of temperature gave maximal activity for the production of β-CD at 65°C, pH 6.0, and 7 1.5 mmol of β-CD/(min·mg of protein), whereas for γ-CD it was 9.1 m mol of γ-CD/(min·mg of protein) at 70°C and pH 8.0. For long contact times, the bestuse of the enzymatic activity occurs at 60°C oratalower temperature, and the reaction pH may be selected to increase the vield of a desired CD.     

Enhancement of selectivity for producing γ-cyclodextrin

The production of cyclodextrins (CDs) by cyclodextrin-glycosyl-transferase (CGTase) from Bacillus firmus was studied, with respect to the effect of the source of starch upon CD yield and on the selectivity for producing γ-CD. Cyclodextrin production tests were run for 24 h at 50°C, pH 8.0, and 1 mg/L of CGTase, and substrates were maltodextrin or the starches of rice, potato, cassava, and corn hydrolyzed up to D. E. 10. Cornstarch was the best substrate for producing γ-CD. Later, glycyrrhizin (2.5% [w/v]), which forms a stable complex with γ-CD, was added to the cornstarch reaction medium and increased the yield of γ-CD to about four times that produced with only maltodextrin, but the total yield of CDs remained practically unchanged. Therefore, the results showed that the studied CGTase is capable of giving relatively high yield of γ-CD in the presence of glycyrrhizin as complexant and cornstarch as substrate.     

Enhanced ternary 1:2 host–guest complexation of amino-γ-cyclodextrins with 2-anthracenecarboxylic acid

The complexation behavior of 6-amino-6-deoxy-γ-cyclodextrin (CD), 6^A,6^X-diamino-6^A,6^X-deoxy-γ-CDs and 3^A-amino-3^A-deoxy-altro-γ-CD with 2-anthracenecarboxylic acid (AC) was studied by NMR, UV–vis and circular dichroism spectroscopy. These modified γ-CD derivatives were found to form stable 1:2 host-guest ternary complexes with AC in aqueous solution. Compared with native γ-CD, the primary-face-aminated γ-CDs exhibited remarkably enhanced overall association constants as a result of the additional electrostatic interactions between the oppositely charged host and guest. In contrast, the ternary complex formation of the secondary-face-aminated γ-CD with AC was hindered.     

Effect of cyclodextrins on physico-chemical and release properties of Eudragit RS 100 microparticles containing glutathione

The objective of this work was to develop a novel microparticulate system based on the mucoadhesive polymer Eudragit-RS 100 and cyclodextrins (CDs), potentially useful for the oral administration of Glutathione (γ–glutamylcysteinylglycine, GSH). For this purpose, an oil-in-oil (O/O) emulsion-solvent evaporation method was used for the preparation of microparticles (MPs) containing GSH alone or together with one of the following CDs: α-, β-, γ-, methyl-β-(Me-β-), hydroxypropyl-β-(HP-β-) or sulfobutylether-β-cyclodextrin (SBE_7m-β-CD). MPs were obtained by emulsifying a mixture of Eudragit RS 100, GSH, CD and magnesium stearate in acetone or acetonitrile with a mixture of liquid paraffin and Span 80. Size, encapsulation efficiency, and drug release of the prepared MPs were evaluated. The results clearly indicated that all the examined properties were dependent on the water-miscible solvents and CD used. In particular, MPs prepared by using acetone or acetonitrile showed different size distributions with mean diameters in the ranges 82–350 and 15–22 μm, respectively. Moreover, encapsulation efficiency values were found to be high in all cases (71–99%) and was significantly affected by the CD type. The GSH release rates were evaluated employing dissolution media with different pH values (1.2, 6.8 and 7.4) and the following rank order was obtained for MPs prepared using acetone: MPs incorporating Me-β-CD > MPs without CD > MPs incorporating the remaining CDs. On the other hand, MPs prepared using acetonitrile gave the highest GSH release rate. Finally, stability of GSH encapsulated in MPs containing HP-β-CD to enzymatic attack by pepsin A, α-chymotrypsin, and γ-glutamyltranspeptidase was also investigated.     

New gamma-ray intensities for the <Superscript>14</Superscript>N(n,γ)<Superscript>15</Superscript>N high energy standard and its influence on PGAA and on nuclear quantities

The ¹⁴N(n,γ)¹⁵N reaction is a primary γ-ray source for high energy calibration of detectors. The relative γ-ray-intensities of ¹⁵N and the relative γ-ray detection efficiency function have been simultaneously determined up to 10 MeV from γ-peak areas alone. Absolute γ-ray-intensities were obtained with proper renormalization to known absolute intensity. The influence of these new intensity values are assessed for use in PGAA. Any consistently used set of calibration intensities applied in the creation of library values and for analysis do not influence the concentrations. Contrary to this, quantities based on sums of γ-ray cross sections may provide different answers with the new ¹⁵N intensities and they give means to validate them.     

Calculation of cyclodextrin-mediated enantiomer ratio shifting of racem norgestrel in aqueous solutions

Enantioselective solubility of rac-norgestrel was found in the presence of γ-cyclodextrin or hydroxypropyl-γ-cyclodextrin. In both cases the efficacious enantiomer was dissolved in greater extent. Calculating the molar absorptivity and molar ellipticity spectra of the γ- and hydroxypropyl-γ-cyclodextrin aqueous complexes, a simple and rapid direct circular dichroism (CD) spectrometric method was obtained for the determination of the enantiomer ratio in aqueous solutions.     

The use of non-destructive high energy gamma photon activation for trace element survey analysis

An empirical study has been made of the potential of high energy γ photon activation and high resolution γ-ray spectrometry for the survey analysis of trace elements in a variety of materials. Human blood, urine, bone ash, standard glass (NBS, SRM 612) and air particulates, along with synthetic multi-element standards, have been studied following irradiation with γ photons of maximum energy 17–45 MeV. Elements found to be suited to determination by γ activation include Sb, As, Bi, Cd, Cs, Ca, Ce, Cr, Fe, Au, Pb, Mg, Mo, Ni, Nb, Rb, Sr, Tl, Ti, Tm, Zn and Zr. γ spectra, elemental concentrations measured, and/or limits of detection observed, for the matrices studied are given.