New antimalarial drugs

Approximately 40% of the world population live in areas with the risk of malaria. Each year, 300-500 million people suffer from acute malaria, and 0.5-2.5 million die from the disease. Although malaria has been widely eradicated in many parts of the world, the global number of cases continues to rise. The most important reason for this alarming situation is the rapid spread of malaria parasites that are resistant to antimalarial drugs, especially chloroquine, which is by far the most frequently used. The development of new antimalarial drugs has been neglected since the 1970s owing to the end colonialism, changes in the areas of military engagement, and the restricted market potential. Only in recent years, in part supported by public funding programs, has interest in the development of antimalarial drugs been renewed. New data available from the recently sequenced genome of the malaria parasite Plasmodium falciparum and the application of methods of modern drug design promise to bring significant development in the fight against this disease.     

Determination of heavy metal complexes with humic substances by HPLC/ICP-MS coupling using on-line isotope dilution technique

An isotope dilution mass spectrometric (IDMS) method has been developed for the simultaneous determination of the complexes of 11 heavy metals (Ag, Cd, Cu, Mo, Ni, Pb, Tl, U, W, Zn and Zr) with humic substances (HS) by coupling HPLC with ICP-MS and applying the on-line isotope dilution technique. The HPLC separation was carried out with size exclusion chromatography. This HPLC/ICP-IDMS method was applied to samples from a brown water, ground water, sewage and seepage water as well as for a sample containing isolated fulvic acids. The total contents of heavy metals and of their complexes were analyzed in these samples with detection limits in the range of 5–110 ng/L. The analysis of heavy metal/HS complexes from the different waters resulted in characteristic fingerprints of the distribution pattern of heavy metals in the separated HS fractions. A comparison between the total heavy metal concentrations and their portions bound to humic substances showed distinct differences for the various metals. Simultaneous ¹²C detection was used for the characterization of HS complexes not identified by UV detection and for the determination of relative DOC concentrations of chromatographic peaks. Received: 21 February 1997 / Revised: 27 May 1997 / Accepted: 28 May 1997     

NMR spectroscopic characterization of millisecond protein folding by transverse relaxation dispersion measurements

The cold shock protein CspB adopts its native and functional tertiary structure on the millisecond time scale. We employed transverse relaxation NMR methods, which allow a quantitative measurement of the cooperativity of this fast folding reaction on a residue basis. Thereby, chemical exchange contributions to the transverse relaxation rate (R(2)) were observed for every residue of CspB verifying the potential of this method to identify not only local dynamics but also to characterize global events. Toward this end, the homogeneity of the transition state of folding was probed by comparing Chevron plots (i.e., dependence of the apparent folding rate on the denaturant concentration) determined by stopped-flow fluorescence with Chevron plots of six residues acquired by R(2) dispersion experiments. The coinciding results obtained for probes at different locations in the three-dimensional structure of CspB indicate the ability and significance of transverse relaxation NMR to determine Chevron plots on a residue-by-residue basis providing detailed insights on the nature of the transition state of folding.     

Chemie polyfunktioneller liganden LXIII. Adamantankäfigverbindungen mit den heteroelementen arsen,stickstoff und silizium

The reaction of 1,1,1-tris(diiodarsinomethyl)ethane, CH₃C(CH₂AsI₂)₃ (I), with i-C₃H₇NH₂, n-C₄H₉NH₂, C₆H₅NH₂, p-CH₃C₆H₄NH₂ and [(CH₃)₃Si]₂NH in the presence of (C₂H₅)₃N as auxiliary base in THF gives the adamantane cage compounds CH₃C(CH₂AsNC₃H₇)₃ (III), CH₃C(CH₂AsNC₄H₉)₃ (IV), CH₃C(CH₂AsNC₆H₅)₃ (V), CH₃C(CH₂AsNC₆H₄CH₃)₃ (VI) and CH₃C[CH₂AsNSi(CH₃)₃]₃ (VII). VII is also obtained in the reaction of I with NaN[Si(CH₃)₃]₂. The by-product (CH₃)₃SiO(CH₂)₄I (VIII) could be isolated in both syntheses of VII. All compounds have been characterized by mass spectrometry and infrared, Raman and ¹H NMR spectroscopy.     

Boride-based nano-laminates with MAX-phase-like behaviour

MAX-phases being usually composed of transition metals, group A elements and carbon/nitrogen are considered interesting materials for many applications because of their tremendous bulk modulus, “reversible” plasticity, and machinability. This is mainly due to their unique kind of bonding comprising covalent, ionic as well as metallic bonds providing “easy” planes of rupture and deformability due to the layered crystal structures.In transition metal boride systems, similar types of bonding are available. In particular the W₂B₅-structure type and its stacking variations allow the synthesis of strongly layered crystal structures exhibiting unique delamination phenomena.The paper presents ab initio calculations showing the similarities of bonding between the ternary carbides and the corresponding ternary or quaternary borides. Formation of boride-based nano-laminates from auxiliary liquid phases, from the melt as well as during sintering and precipitation from supersaturated solid solutions will be discussed by means of SEM and TEM studies. The role of impurities weakening the interlayer bonding will be addressed in particular. The pronounced cleavage parallel to the basal plane gives rise for crack deflection and pull-out mechanisms if the laminates are dispersed in brittle matrices such as boron carbide, silicon carbide or other transition metal borides.     

Excess Molar Volumes and Liquid–Liquid Equilibria of the Ionic Liquid 1-Methyl-3Octyl-Imidazolium Tetrafluoroborate Mixed with Butan-1-ol and Pentan-1-ol

Experimental densities were measured for the system 1-methyl-3-octyl-imidazolium tetrafluoroborate [OMIM][BF₄] + butan-1-ol, + pentan-1-ol at 298.15 K and ambient pressure using a vibrating tube densimeter, taking into account the influence of the viscosity correction. Excess molar volumes V^E have been determined. V^E is quite small and negative in the alcohol-rich range of the mixture composition and positive in the alcohol-poor range. LLE data of [OMIM][BF₄] + pentan-1-ol have been measured using a laser light scattering cell for detecting cloud points at different compositions in the temperature range of 282–292 K. A miscibility gap with an upper critical solution temperature (UCST) of 292 K has been found.     

Quantitative Bestimmung von DNA in Geweben durch Thymin-Analyse

Zusammenfassung Es wird über eine DNA-Bestimmung in biologischem Material durch Hochdruckflüssigkeits-Chromatographie an sphärischen Ionenaustauschern berichtet. Thymin wird durch Hydrolyse lyophilisierter Gewebe freigesetzt, durch Sublimation gereinigt und flüssigkeits-chromatographisch bei etwa 150 at Eingangsdruck bestimmt. Die Ausbeute des Verfahrens wird durch Isotopenverdünnungsanalyse überprüft. Der Einfluß von pH-Wert und Konzentration der Elutionspuffer und der Säulentemperatur wird ermittelt. Die untere quantitative Nachweisgrenze der Methode liegt bei etwa 0,5 g DNA in Geweben, die relative Standardabweichung betrug 10%.

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Quantitative determination of DNA in tissues by thymine-analysisII. Determination by high-pressure ionexchange liquid chromatography

A determination of DNA in biological material by high pressure, liquid chromatography of thymine on spherical ion-exchange resins is presented. After lyophilizing and hydrolyzing the tissues, thymine is separated by sublimation and determined by means of liquid chromatography at 150 at. Yields are controlled by isotope dilution analysis. Investigations on the effect of pH and concentration of eluents and of temperature are reported. The method is suitable for a minimal amount of 0.5 g DNA in tissues with a relative standard deviation of 10%.

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Teil I: diese Z. 259, 177 (1972).

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Geodia cydonium wurde uns dankenswerterweise von der meeresbiologischen Forschungsgruppe, Leitung Herr Prof. Dr. R. K. Zahn, zur Verfügung gestellt.     

Isolierung von Magnesium aus biologischem Material für die massenspektrometrische Isotopenanalyse

Magnesium is precipitated as hydroxide after elimination of interfering elements by means of ion-exchange procedures (phosphate, iron, trace elements) and masking with EDTA (calcium). The sample is applied in form of MgCl₂ to the tungsten filament of an 1-filament-ion-source for surface ionization.