Inclusion Complexation of a Seleno-Organic Antioxidant, Ebselen, with Cyclodextrins in Aqueous Solution

The interaction of ebselen, 2-phenyl-1,2-benzisoselenazol-3(2H)-one, a novel neuroprotective agent, with cyclodextrins (CyDs) in aqueous solution was studied by the solubility method and spectroscopic methods. The ability of sulfobutyl ether -CyD (SBE7--CyD, average degree of substitution= 6.2) to solubilize ebselen was greater, and its stability constant (> 2000 M^-1) was significantly higher than those (< 1000 M^-1) of other CyD complexes employed. The stability constant of the complexes rose as hydrophobicity of the substituents of CyDs increased, whereas it was negligibly affected by change in ionic strength of the medium, indicating a significant contribution of hydrophobic interaction in the complexation. SBE7--CyD gave positive and negative CD bands at around 320 and 350 nm, respectively, indicating that the guest is embedded in the asymmetric locus of the CyD cavity. ¹H-NMR spectroscopic studies suggested that the mono-substituted benzene ring of ebselen is preferably included in the cavity of SBE7--CyD. The results indicate that SBE7--CyD is useful as a solubilizing agent for ebselen.     

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%).     

Complexation of Oleuropein and trans-Cinnamic Acid with Cyclodextrins

The complexation of oleuropein and trans-cinnamic acid with -, -, and -cyclodextrin has been studied in aqueous model systems by light scaterring. The influence of various parameters (pH, concentration, reaction time, nature of cyclodextrin) has been thoroughly examined. The formation of binary (1:1) inclusion complexes and the higher inclusion ability of -CD for both compounds has been indicated. Trans-cinnamic acid was extracted from olive olive oil following its complexation with -CD at satisfactory recovery levels.     

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.     

A kinetic method for the direct determination of cellobiose hydrolysis by β-glucosidases

TheSomogyi—Nelson colorimetric method is applied in a new manner which is more suitable for following the kinetics of cellobiose hydrolysis catalyzed by -glucosidase (EC 3.2.1.21). TheSomogyi—Nelson colour reagent, which is a mixture of the solutions of the reagent ofSomogyi and that ofNelson in a volume ratio of 1:1, is added to the enzyme-substrate solution at the very start of the reaction. The colour reagent reacts with the product (D-glucose). Under the reaction conditions (0.1M acetate buffer,pH = 5.0 and temperature 37°C) the colour reagent does not affect the enzyme activity. The method excludes any inhibition of the product, owing to the continuous removal of the latter by the colour reagent. The method suggested has been applied to monitor cellobiose hydrolysis with -glucosidase, contained in four cellulase enzyme preparations from various fungal sources. The values of theMichaelis parameters (Km, V) were determined.

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Eine kinetische Methode zur Verfolgung der Hydrolyse von Cellobiose durch ß-Glucosidasen

Zusammenfassung Die kolorimetrische Methode nachSomogyi undNelson wird nach einem neuen Verfahren zur Verfolgung der Kinetik der hydrolytischen Spaltung von Cellobiose, katalysiert durch -Glucosidase (EC 3.2.1.21), angewandt. Das Farbreagenz nachSomogyi undNelson (Mischung der Reagenzien vonSomogyi undNelson im Volumenverhältnis 1:1) wird der Enzym-Substrat-Lösung zu Beginn der Reaktion hinzugefügt. Das Farbreagenz tritt mit derD-Glukose in Reaktion, wobei unter den gegebenen Reaktionsbedingungen (0,1M Azetatpuffer,pH = 5,0 und 37°C) die Enzymaktivität nicht beeinflußt wird. Die entwickelte Methode wurde zur Verfolgung der Hydrolyse von Cellobiose durch ß-Glucosidasen, die in vier Enzympräparaten aus verschiedenen Pilzstämmen enthalten waren, angewandt. Es wurden dieMichaelis-Parameter (Km, V) bestimmt.

     

Chemical Composition of Certain Sedum Species of Kazakhstan

The chemical composition of sevenSedumspecies growing in Kazakhstan was studied by chromatography. The contents of seven groups of natural compounds were determined. Comparison with markers and literature data identified 24 compounds including 9 that have not been described previously inSedumspecies     

NMR Investigations of the Inclusion of Thyroxine and Derivatives in Natural Cyclodextrins

Thyroxine T4 and its derivatives (T3, T2) are very sparingly soluble in aqueous solutions even in the form of salts. In the presence of or -cyclodextrins and in buffered basic solution, their solubilities are increased by inclusion in the cavity. The inclusion of these hormones in cyclodextrins was investigated by 1H-NMR in order to derive the influence of the number and position of the iodine atoms, and of the ionization state of the phenol group on the inclusion geometries.     

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.     

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.     

Influence of cyclodextrins on nitrosation of drugs

The World Health Organization issued a nitrosation procedure (NAP Test) which allows to carry out nitrosation under standard conditions. It has proved that the in vitro reaction rates of the fast nitrosatable drugs piperazine, cimetidine and ethambutol are not influenced by -, - and -cyclodextrin. On the contrary, -, -cyclodextrin and heptakis-2,6-di-O-methyl--cyclodextrin enhance the nitrosation of the slower nitrosatable 1-ephedrine and fencamfamine significantly. This possible reaction must be considered if nitrosatable drugs are formulated with cyclodextrins to be administered to human beings.     

Photometric determination of palladium with the inclusion complex 1,2-Diaminoanthraquinone-β-cyclodextrin as ligand

1,2-Diaminoanthraquinone forms a 11 inclusion complex with-cyclodextrin in aqueous media and at different pH. This can be employed to solubilize the anthraquinone in water for use as a ligand for metal ions. This ligand can be used to determine palladium at trace levels spectrophotometrically. The limit of detection is 11 ng/ml and the R.S.D. is 2.1%. The performance can be improved by using derivative spectrometry.     

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.     

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.     

An Investigation of Inclusion Complexes of Cyclodextrins with Phenylurea Herbicides by Photochemically-Induced Fluorescence. Analytical Applications

The effect of -cyclodextrin (-CD) and hydroxypropyl--cyclodextrin (HP--CD) upon the photochemically-induced fluorescence (PIF) properties of four phenylurea herbicides, including linuron, diuron, isoproturon and neburon has been studied. Photochemical conversion of these nonfluorescent herbicides into strongly fluorescent photoproducts was shown to occur in -CD and HP--CD aqueous media. The influence of pH, UV irradiation time and photoproduct stability on the fluorescence intensity was also investigated. In addition, the stoichiometry and formation constants of the complexes formed between herbicides and -cyclodextrin (-CD) or 2-hydroxypropyl--cyclodextrin (HP--CD) were determined. The formation constant values, ranging from 184 ± 40 to 1498 ± 245 M^-1, were calculated by applying the iterative nonlinear regression (NLR) approach to the PIF data. Linear calibrations graphs were established in the interval 1–12 g/mL, for diuron, linuron and neburon. The IUPAC limits of detection ranged between 580 and 700 ng/mL, according to the compound. Application to the analysis of phenylurea herbicides in spiked river water was also described.     

Solubility Enhancement of Low Soluble Biologically Active Compounds by β-Cyclodextrin and Dimethyl-β-cyclodextrin

The solubility enhancement of triflumizole by complexation with -cyclodextrin and with dimethyl--cyclodextrin is compared with respect to the different physico-chemical properties of the host molecules. Although the inclusion reaction constants are rather similar for both complexation reactions, a completely different temperature dependence of the host-guest interaction is observed, which indicates a change of the reaction mechanisms. Moreover, the influence of ethanol as cosolvent is studied.     

Structural Features of the β-CD Complexes with Naringin and its Dihydrochalcone and Aglycon Derivatives by 1H NMR

The -CD inclusion complexes of naringin 1, naringin dihydrochalcone 2 and the aglycon of naringin dihydrochalcone 3 have been investigated by ¹H NMR spectroscopy. Continuous variation plots show the stoichiometry of all complexes to be 1 : 1. Thestructure of complexes was determined from 2D ROESY and 1D ROE experiments. For 1 and 2 the inclusion involves the aromatic rings leaving the disaccharide unit -L-Rha-(1-2)--D-Glc outside the -CD cavity. For naringin 1 the inclusion occurs preferentially from the wider rim of the -CD truncated cone with the terminal phenolic ring deeply inserted into the -CD cavity while for naringin dihydrochalcon 2 it occurs from the side of the -CD narrower rim. The -CD/aglycon 3 complex exists as an equilibrium of the two inclusion modes.     

Selective reduction of the acyl group in cyclic α-acyl-β-dicarbonyl compounds with sodium cyanoborohydride. Efficient synthesis of cyclic α-alkyl-β-dicarbonyl compounds

Efficient synthesis of cyclic -alkyl--dicarbonyl compounds of the cyclopentane, cyclohexane, tetronic acid, and -pyrone series from the corresponding cyclic -acyl--dicarbonyl compounds under the action of NaBH₃(CN) in a THF--HCl system is described.     

Synthesis ofN-alkylamides of 3-fluoroalkylaziridine-2-carboxylic acids

The N-alkylamides of 3-fluoroalkylaziridine-2-carboxylic acids have been prepared for the first time by the interaction of ethyl 0-fltioroalkyl-,-dibromocarboxylates with primary amines.Prepared by a known procedure;² characteristics of previously unknown ester1b are given in the Experimental section.     

Formulation and Preliminary in vivo Testing of Rufloxacin-Cyclodextrin Ophthalmic Solutions

Aim of the present work was to investigate the effect of somecyclodextrins (CDs) on the solubility and ocular bioavailability of rufloxacin base (RUF), with theultimate goal of developing an ophthalmic formulation. Phase solubility studies of RUF inpH 7.4 buffer were carried out in the presence of -cyclodextrin (-CD),hydroxypropyl--cyclodextrin (HP--CD) and -cyclodextrin(-CD). The effect of hydroxypropyl methylcellulose (HPMC) on RUF solubility was evaluated after heating the solutionscontaining HP--CD at 120 °C.A significant enhancement of RUF solubility was achieved by associatingthe drug with CDs, particularly HP--CD. This CD formed with RUF a less stablecomplex than that formed by -CD, but did not suffer the solubility limitations ofthe parent CD, and showed a higher solubilizing capacity than -CD. Addition of 0.25%(w/v) HPMC to solutions containing HP--CD increased the solubilizing effect of this CD,thus allowing reduction of the amount necessary for solubilization of 0.3% (w/v) RUF.Preliminary pharmacokinetic data in rabbits indicated that theocular bioavailability of 0.3% (w/v) RUF solubilized by HP--CD was higher when compared witha 0.3% (w/v) RUF suspension used as reference.     

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.