In vitro nitrosation of ephedrine in the presence of cyclodextrins

-, and -cyclodextrin and heptakis-2,6-di-O-methyl--cyclodextrin enhance the nitrosation rate of l-ephedrine if the nitrosation assay procedure (NAP test) is applied. During this reaction with -cyclodextrin a solid inclusion compound of -cyclodextrin andN-nitrosoephedrine precipitates. Solubilities and stabilities of inclusion compounds of the cyclodextrins with ephedrine and nitrosoephedrine, respectively, explain especially the catalytic effects of some cyclodextrins on ephedrine.Part of the PhD thesis of V. Wedelich, Freie Universität Berlin, 1985.     

Nitrosation of mefenorex in the presence of cyclodextrins

- and -Cyclodextrin (CD) and heptakis-2,6-di-O-methyl--cyclodextrin (DIMEB) form soluble inclusion compounds with mefenorex (MEF); with -CD a partial inclusion occurs. No solid inclusion compound could be obtained with the four CDs. -, -CD and DIMEB, but not -CD, enhance the nitrosation rate of MEF if the nitrosation assay procedure (NAP test) is applied. During this reaction with - and -CD, solid inclusion compounds of the CDs and nitrosomefenorex (NMEF) precipitate.Part of the Ph.D. thesis of V. Wedelich, Freie Universität Berlin, 1985.     

Semiempirical calculations on cyclodextrins

In order to obtain information on the different reactivities of the hydroxyl groups of the glucopyranose units or the inclusion complex formation mechanism, the charge distributions and the geometrical constraints must be determined. Geometry optimizations, employing the AM1 semiempirical method, have been performed for -D-glucopyranose, –,–, and -cyclodextrins. The data obtained were compared with X-ray diffraction data of the cyclodextrins.Dedicated to Professor József Szejtli.     

Effect of Cyclodextrins on the Chemical Stability of ST1435, a Contraceptive Steroid Progestin, in Aqueous Solution

The influence of cyclodextrins (CDs) on the chemical stability of the contraceptive steroid progestin, ST1435, in aqueous solution has been studied using reversed phase high performance liquid chromatography. The effects of CD structure, temperature, and CD concentration on the rate of degradation were investigated. It was found that the drug degraded to different extents following a pseudo-first order reaction mechanism. The presence of the host molecules affected the degradation rate as a result of complexation which might result in protection of the labile moiety of the drug molecule against degradation. Hydroxypropyl--cyclodextrin (HP--CD) and hydroxyethyl--cyclodextrin (HE--CD) retarded the degradation in contrast to -cyclodextrin (-CD) which accelerated the steroid degradation. The stabilizing action of HP--CD is larger than that of HE--CD. The degradation rate increased upon increasing temperature and the Arrhenius equation is valid. Lineweaver-Burk equation analysis indicated that the steroid included inside the CD cavity degraded three times more slowly than did the free ST1435 in solution. This equation further supported the formation of a 1 : 1 inclusion complex between ST1435 and HP--CD with a stability constant of 934.5 M-1 at 65°C.     

Interaction of fluoroalkyl-containing β-diketones with amines

The composition of products of the interaction of asymmetric fluoroalkyl-containing -diketones with amines was studied. Mixtures of regioisomeric -aminovinylketones and products of cleavage and secondary condensation are formed, depending on the temperature, the solvent, the nature of the fluorinated and nonfluorinated substituents in the -diketone, and the basicity of the amine. The major product is a -aminovinylketone in which the NH₂ group is removed from the fluoroalkyl substituent. No -aminovinylimines, products of condensation involving two electrophilic centers, were observed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2278–2284, September, 1996.     

Phosphorescence of lyophilized complexes between cyclodextrins andβ-arylpropiophenones

-Arylpropiophenones do not phosphoresce in homogeneous solution as a result of excited state quenching by the -aryl group. In the presence of cyclodextrins the parent substrate, -phenylpropiophenone, shows readily detectable phosphorescence. The complexes show strong phosphorescence after lyophilization to dryness. The phosphorescence intensity of ring-substituted derivatives is strongly dependent upon molecular size and cavity dimensions, suggesting that the -arylpropiophenones can be used to probe these properties.Issued as NRCC-23907     

Investigation of gas chromatographic interaction mechanism on permethylated cyclodextrins by molecular modelling

Summary The capillary gas chromatographic retention behavior of -pinene and tricyclene has been investigated on stationary phases of different polarities. On all but one of the columns employed, tricyclene eluted before -pinene; only permethylated -cyclodextrins dissolved in moderately polar polisiloxanes gave a reversed elution order. The intermolecular interactions which caused the unexpected retention behavior were investigated in detail, applying methods of computer simulation. To achieve this, we have developed a calculation algorithm on the basis of molecular mechanical optimizations and programmed it in a macro. This makes it possible to systematically investigate a given configuration space in which all the possible interactions can take place. It was shown that permethylated -cyclodextrin as host molecule for both guest molecules offers an optimum cavity size. As a result the number of energetically favorable contacts between host and guest molecules as well as the strength of the interactions in this stationary phase were larger. As a consequence the elution order, normally only influenced by the vapor pressure of the compounds at a given temperature, was changed. Nonspecific interactions played an especially important role for these kinds of substances.     

Photochemical addition of diethyl ether to β,β,β',β'-tetrakis(trifluoromethyl)divinyl ether

The 1:1 adducts of diethyl and ,,','-tetrakis(trifluoromethyl)divinyl ether (1),i.e., 3,5-(ee)-bis[2,2,2-trifluoro-1-(trifluoromethyl)ethyl]-2,6-dimethyl-1,4-dioxane (2) (3 isomers) and 4-ethoxy-1,1,1-trifluoro-2-trifluoromethyl-3-[3,3,3-trifluoro-2(trifluoromethyl)propenyloxy]pentane (3), have been obtained by UV-irradiation of a solution of divinyl ether1 in diethyl ether. The X-ray structural investigation of the all-(e)-isomer of dioxane (2) has been carried out.Deceased.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 85–88, January, 1994.     

The Chlorhexidine: beta;-Cyclodextrin Inclusion Compound: Preparation, Characterization and Microbiological Evaluation

The 1 : 2 chlorhexidine : -cyclodextrin(Cx : CD) complex was prepared and characterised using X-ray crystallography, infrared spectroscopy, thermal analysis and nuclearmagnetic resonance. The minimum inhibitory concentration (MIC₅₀) of the chlorhexidine : -cyclodextrin inclusion compoundagainst Streptococcus mutans, Eubacterium Lentum, Fusobacterium nucleatum, Bacteroides fragilis andActinomices actinomycetemcomitans was determined. TheCx : CD inclusion compound inhibited the bacterial growth at a low concentration.     

Improvement of Solubility and Dissolution of 19-Norprogesterone via Inclusion Complexation

In an effort to modify the solubility and dissolution rate of the contraceptive steroid, 19-norprogesterone in order to improve its bioavailability, the cyclodextrin complexation approach was chosen. In solution, the complex formation with -cyclodextrin (-CD), hydroxyethyl -cyclodextrin (HE--CD) and hydroxypropyl -cyclodextrin (HP--CD) was confirmed by using solubility, UV, IR and ¹H-NMR spectrophotometric techniques. The phase solubility diagrams were categorized as A_L-type. The complexing affinity of the CDs investigated were ranked as follows: -CD > HP--CD > HE--CD. The complexation thermodynamic parameters were obtained from the temperature dependence of the dissociation constants. In the solid state, differential scanning calorimetery (DSC) and optical microscopy methods were utilized to characterize the complexes. Dissolution studies showed that such molecularly encapsulated forms offered a marked improvement in the dissolution rate compared to the parent drug.     

In vitro Release Study of Tretinoin from Tretinoin/Cyclodextrin Derivative Complexes

The effects of -cyclodextrin, hydroxypropyl -cyclodextrin and dimethyl -cyclodextrin complexes on the in vitro release of tretinoin gels were investigated. The experiments were carried out in a Franz cell using a silicone membrane as a barrier for the diffusion of the vehicle. Two types of vehicle were compared: a hydroalcoholic gel in which both tretinoin and the inclusion complexes are soluble, and an aqueous gel in which only the complexes are soluble but tretinoin is dispersed. As expected, the release rate of free tretinoin in the hydroalcoholic gel is much faster than in the aqueous gel. However, with the aqueous gel, the cyclodextrin complexation enhances the diffusion rate of the active drug through the membrane, especially with the hydroxypropyl cyclodextrin inclusion compound. The release of tretinoin is related not only to the stability constant of the inclusion, but also to the binding properties of the inclusion compounds to the vehicle.     

Influence of the Structure of Steroid Hormones on Their Association with Cyclodextrins: A High-Performance Liquid Chromatography Study

The association constants of fourteen steroid hormones with - and -cyclodextrin were measured in methanol-water (20 : 80 v/v) at 35 °C using the chromatographic Hummel-Dreyer method. It was found that the greatest influence on the association constants is the structural features of ring A of these compounds but the substituents of ring D also alter the complex stability to an appreciable degree. The measured association constants were considerably greater than the corresponding values measured previously in the medium containing more methanol (45 instead of 20%).     

Stereocontrolled synthesis of low-molecular-weight β-O-glycosides from products of decyclization of acylated oligosaccharide glycals

Low-molecular-weight -O-glycosides with aliphatic polyfunctional aglycones were synthesized by Horner-Emmons olefination of O-glycosylated ,-unsaturated aldehydes prepared by acid opening of the dihydropyran ring in totally acylated lactal, cellobial, and gentiobial.Institute of Organic Chemistry, Ural Branch, Russian Academy of Sciences, 450054 Ufa. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 5, pp. 1176–1181, May, 1992.     

Molecular Interactions and Inclusion Phenomena in Substituted β-Cyclodextrins. Simple Inclusion Probes: H2O, C, CH4, C6H6, NH4 +, HCOO−

Using a simple molecular mechanics approach interaction energy profiles of simple probes (C, CH₄, C₆H₆, H₂O, NH₄ ⁺, and HCOO^-) passing through the center of the -CD ring cavity along the main molecular symmetry axis were first evaluated. Molecular Electrostatic Potential (MEP) values along the same path were also evaluated. The effect of the flexibility of the host -CD molecule together with solute-solvent (H₂O) interactions have been represented by averaging structures of MD calculations for -CD alone and -CD surrounded by 133 H₂O molecules. The effect of various substitutions of -CD has also been evaluated. Small symmetric hydrophobic probes (such as C, CH₄, C₆H₆) are predicted to form stable inclusion complexes with non-substituted and substituted -CDs, the probe position typically being near the cavity center. The stability of the inclusion complexes will increase with increasing size and aliphatic character of the probe. Small polar and charged probes (such as H₂O, NH₄ ⁺, HCOO^-) are predicted to prefer the interaction with the solvent (water) in the bulk phase rather than the formation of inclusion complexes with non-substituted and substituted -CDs. Guest–host interactions in the stable inclusion complexes with hydrophobic probes are almost entirely dominated by dispersion interactions. The MEP reaches magnitudes close to zero in the center of the non-substituted -CD ring cavity and in most of the studied substituted -CDs and shows maximum positive or negative values outside of the cavity, near the ring faces. Substitution of -CD by neutral substituents leads to enhanced binding of hydrophobic probes and significant changes in the MEP profile along the -CD symmetry axis.     

Quantitative and Qualitative Analysis of RAMEB in Soil

An HPLC method has been developed for determination of RAMEB in soil samplescontaminated with hydrocarbons. The extraction efficiency of RAMEB from soils wasfound to depend on the soil properties. The extraction method elaborated results in agood recovery from sandy and loamy soils, but only a poor recovery was obtained from soils of high clay content.A SPE method was worked out to remove the components disturbing the HPLCanalysis, and a one-peak method has been developed for the quantitative analyses.The isomer distribution of RAMEB was characterized by fingerprint chromatograms.The new methods have been applied for determination of RAMEB content in soilsamples from field treatment.     

Conformational Heterogeneity of a Tripeptide in the Solid State and in Solution: Characterization of a γ-Turn Containing Incipient Hairpin in Solution

A terminally blocked tripeptide Boc--Ala-Aib--Ala-OMe 1 with noncoded amino acids forms a novel type of hairpin structure containing a -turn instead of a conventional -turn in the central loop region in solution. This new type structural motif was characterized by NMR and restraint molecular dynamics simulation study. In the solid state peptide 1 adopts an extended backbone conformation and self-assembles to form supramolecular -sheet.     

Synthesis and sorption properties of new hybrid chelating sorbents with β-alanine functional groups

A series of -aminopropylsilylated sorbents was obtained from different oxide supports (silica gels, silica fillers, macroporous glasses, alumina) and by the direct synthesis (hydrolytic polycondensation of tetraalkoxysilanes with -aminopropyltriethoxysilane). The highest degree of immobilization was achieved for silicas, while the most convenient solvent was methanol. Sorbents with -alanine functional groups were obtained by the subsequent reaction with acrylic acid. The degree of -carboxyethylation was 1.3–1.9, and the highest content of functional groups (v_COOH = 3.23 mmol g^–1) was achieved for carboxyethylated xero gel synthesized by the copolycondensation of tetraethoxysilane with -aminopropyltriethoxysilane. The sorbents containing -alanine possess a higher selectivity of Cu²⁺ ion sorption than the initial -aminopropylsilylated sorbents.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2620–2625, December, 2004.     

Kinetics and mechanism of the hydrolysis of sodium carboxymethylcellulose (Na-CMC) by a cellulase complex

TheSomogyi-Nelson colorimetric method is applied in a new manner more suitable for evaluating the kinetics of the enzyme hydrolysis of sodium carboxymethylcellulose (Na-CMC) catalyzed by the cellulase complex. By means of selective inhibition of a chosen enzyme from the cellulase complex it became possible to trace the effect of the other enzymes included in its composition.

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Kinetik und Mechanismus der Hydrolyse von Natriumcarboxymethylcellulose (Na-CMC) durch einen Cellulase-Komplex

Zusammenfassung Die kolorimetrische Methode nachSomogyi undNelson wird nach einem neuen Verfahren zur Verfolgung der Kinetik der hydrolytischen Spaltung von Natriumcarboxymethylcellulose (Na-CMC), katalysiert durch den Cellulase-Komplex, angewandt. Durch selektive Inhibierung eines bestimmten Enzyms des Cellulase-Komplexes kann man die Wirkung der anderen zu seiner gesamten Zusammensetzung gehörenden Enzyme verfolgen.

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Symbols Used E enzyme (E—cellulase;E—exo-cellobiohydrolase;E—-glucosidase) - [E] _w weight concentration of enzymeE - S substrate (Na-CMC—sodium carboxymethylcellulose) - [S]₀ weight concentration of substrateS - I inhibitor (I—lactose;I—calcium chloride;I—condurrite-B-epoxide) - P product (P—oligosaccharides;P—cellobiose;P—D-glucose) - P end product (K , K , K ) - DP degree of polymerization - DS degree of substitution - ES enzyme-substrate complex (E S, E S, E S) - EP enzyme-product complex (E P, E P) - EI enzyme-inhibitor complex (E I, E I, E I) - M _s molecular mass of substrateS - K _s substrate constant (K _s , K _s , K _s ) - K _I inhibitor constant (K _I , K _I , K _I ) - K _m Michaelis-Menten constant - k ₊₁,k ₊₂ (k ₊₂ ,k ₊₂ ,k ₊₂ ) forward rate constants - k _–1 reverse rate constant - ₀ initial rate of reaction - V maximal reaction rate - A change in absorbance - molar absorption coefficient - wavelength Herrn Prof. Dr.Hans Tuppy zum 60. Geburtstag herzlichst gewidmet.     

Calorimetric Behaviour of Anhydrous β-Cyclodextrin at Very Low Temperature

Heat capacities of anhydrous -cyclodextrin were measured between 10 K to 300 K using an adiabatic low-temperature calorimeter. Two distinct types of thermal behaviour were observed in the temperature range 50–130 K, depending on the way the sample was cooled. In the absence of hydration water molecules, we assumed that the two types of thermal behaviour could be attributed to freezing in more or less ordered states of the hydroxyl groups engaged in the intramolecular interglucose flip-flop-type interactions.     

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.