4-Aminobicyclo[2.2.2]octanone Derivatives with Antiplasmodial and Antitrypanosomal Activities

Summary. 4-Aminobicyclo[2.2.2]octanones were converted to their N-oxides and to 4-aminobicyclo[2.2.2]octanes. Furthermore, the 6,7-bis-(4-methoxyphenyl) analogues were synthesized. All products were screened for their activities against Trypanosoma b. rhodesiense and Plasmodium falciparum. The pharmacological results were compared with those of formerly tested bicyclo[2.2.2]octanones and bicyclo[2.2.2]octanols. Structure-activity relationships are discussed.Received April 8, 2003; accepted April 14, 2003 Published online September 25, 2003     

Access to the structures of fluoromagnesium compounds: synthesis and structural characterization of the β-diketiminato magnesium fluoride [{CH(CMeNAr)2}Mg(μ-F)(THF)]2·toluene

β-Diketiminato magnesium fluoride [{CH(CMeNAr)₂}Mg(μ-F)(THF)]₂·toluene (Ar=2,6-i-Pr₂C₆H₃, 2·toluene) was synthesized. The molecular structure of 2 revealed for the first time, the double fluoro bridge feature between the two magnesium atoms with a typical MgF bond length (average 1.95 Å).     

Adsorption-penetration studies of glucose oxidase into phospholipid monolayers at the 1,2-dichloroethane/water interface.

The interaction between glucose oxidase (GOx) and phospholipid monolayers is studied at the 1,2-dichloroethane/water interface by electrochemical impedance spectroscopy. Electrochemical experiments show that the presence of GOx induces changes in the capacitance curves at both negative and positive potentials, which are successfully explained by a theoretical model based on the solution of the Poisson-Boltzmann equation. These changes are ascribed to a reduced partition coefficient of GOx and an increase of the permittivity of the lipid hydrocarbon domain. Our results show that the presence of lipid molecules enhances the adsorption of GOx molecules at the liquid/liquid interface. At low lipid concentrations, the adsorption of GOx is probably the first step preceding its penetration into the lipid monolayer. The experimental results indicate that GOx penetrates better and forms more stable monolayers for lipids with longer hydrophobic tails. At high GOx concentrations, the formation of multilayers is observed. The phenomenon described here is strongly dependent on 1) the GOx and lipid concentrations, 2) the nature of the lipid, and 3) the potential drop across the interface.     

The synthesis and characterisation of 1′-ethynyl-2,5-dimethylazaferrocene and derivatives

The synthesis of 1′-ethynyl-2,5-dimethylazaferrocene is reported along with its cyclic voltammetry measurements and the X-ray structure determination of its W(CO)₅-complex. Basic coordination and organic chemistry of 1′-ethynyl-2,5-dimethylazaferrocene is also presented via derivatives incorporating cis-Pt(dppe) and Si(Et)₃ units.     

Conformation-dependent change in antitumor activity of linear and branched (1----3)-beta-D-glucans on the basis of conformational elucidation by carbon-13 nuclear magnetic resonance spectroscopy.

The antitumor activity of (1----3)-beta-D-glucans was tested in order to clarify its conformation-dependent response together with conformational elucidation by carbon-13 nuclear magnetic resonance (13C-NMR) spectroscopy. It was shown that the following three conformations, single chain, single helix and triple helix, are readily distinguished by the high-resolution solid-state 13C-NMR method. It turned out that preparations of linear (1----3)-beta-D-glucans of a triple helical conformation were ineffective in the inhibition of tumor growth. These linear (1----3)-beta-D-glucans were converted to an effective form in the inhibition of tumor growth when they were lyophilized from dimethyl sulfoxide (DMSO) solutions as a result of a conformational change from the triple helical to the single chain forms. They were not effective, however, when assayed in DMSO solution. In contrast, it was found that a branched (1----3)-beta-D-glucan is effective not only in either saline solutions of the triple helical sample or the lyophilized sample from DMSO, but also in DMSO solution. The aforementioned drastic change in antitumor activity was interpreted in terms of resulting conformational changes as analyzed by the 13C-NMR method.     

Ein Beitrag zur ?nologie und ?kologie von Selen

Summary Little is known about selenium contents in alcoholic beverages, especially in wine, because no reliable determination method was available so far. A procedure for the detection of selenium in the pg- and low ng-range was developed, which uses the hydride-generation-condensation-AAS (HGC-AAS). Selenium contents in 103 German wines of the year vintages 1950 until 1985 were determined. In mean they range between 0.29 and 0.79 g/l Se and show a certain dependence from the geological soil formation and the wine species. Corresponding vineyard soils from Ingelheim (Rheinhessen, FRG) contain 0.18–0.44 mg/kg Se, mean 0.24 mg/kg Se, 10% of it is available for plants. The distribution of selenium in grape berries shows selenium-rich seeds and — with red wine species — selenium-rich skins. Higher selenium contents by contamination were observed near an industrial location. The behaviour of selenium in the vegetation cycle is pursued. The selenium depletion during fermentation may amount to 60%. All results are summarized in the so-called trace element vinogram. Selenium hence is a regular and natural constituent part of wine.

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Herrn Prof. Dr. R. Neeb zum 60. Geburtstag gewidmet     

Phase Relations in the Ni–Mn–Ga Ternary System and Aging Effect on Shape Memory Properties of Ferromagnetic Ni<Subscript>2</Subscript>MnGa Sputtered Films

Summary. Isothermal sections of the Ni–Mn–Ga ternary phase diagram at 1073 and 1273 K were investigated over a wide range of alloy compositions. The range of the β-Ni₂MnGa phase, its equilibria with the γ-(Mn, Ni), α′-Ni₃Ga, and γ-Ni₃Ga₂ phases, and the liquidus and solidus lines were determined experimentally. The aging effect on the shape memory effect (SME) of Ni₂MnGa sputtered films was also investigated. The two-way SME of the constraint-aged films was confirmed by the temperature change.     

A density functional study on magnetic exchange interaction between Mn(II) ion and nitronyl nitroxide radical in <Emphasis Type="Italic">trans</Emphasis>-and <Emphasis Type="Italic">cis</Emphasis>-metal-radical complexes

The magneto-structural correlation between a Mn(ll) ion, coordinated in an octahedral environment, and two nitronyl nitroxide radical ligands in trans- and cis-metal-radical complexes is investigated by the broken symmetry (BS) approach within density functional theory (DFT). The dependences of coupling constants J on three structural parameters: (i) bond angle θ (Mn-O-N (nitroxide)); (ii) rotating angle ψ, defined by the nitronyl nitroxide radical plane rotating around the axial Mn-O (nitroxide); (iii) bond distance R (Mn-O (nitroxide)) are directly calculated. Our calculations showed that both trans- and cis-Mn(ll)-radical complexes behave a stronger antiferromagnetic interaction, consistent with experiments. In view of molecular orbital theory, the direct exchanges, including σ-type and π-type exchanges, are responsible for the magnetic exchange pathways. There is a preferable linear correlation between the calculated coupling constants J and the overlap integral squares S b between the local magnetic orbitals at the various rotating angle ψ at the fixed bond angle θ and bond distance R, in both trans- and cis-Mn(ll)-radical complexes.     

A simplified assay of furosemide in plasma and urine by high-pressure liquid chromatography.

A simplified high-pressure liquid chromatograhic method for determination of furosemide in plasma and urine has been developed using a fluorometric detector directly coupled to the column effluent. The method includes an ether extraction from acidified biologic samples. The mobile phase used for chromatography on a reversed-phase column (C15 hydrocarbon permanently bonded to silica particles) is sufficiently acidic to induce fluorescence of furosemide. The methylester of furosemide is employed as an internal standard. The sensitivity is 0.1 and 0.25 microgram per ml plasma and urine, respectively. The applicability to pharmacokinetic studies of furosemide is shown.