Durch Umsatz von Kaliumthoriumnitrat K2Th(NO3) 6 in flüssigem Ammoniak mit steigenden Mengen Kaliumamids wurden folgende Bodenkörper erhalten: Thoriumimido‐diamid HNTh(NH2)2(A), (HN)2ThNH2K (I), HNTh(NH2)3K (II), Th2(NH)3(NH2)4K2 (III). Alle Reaktionsprodukte sind nicht kristallin und stellen mehr oder weniger hochpolymere Verbindungen dar. Das wahrscheinlich primär entstehende Thorium(IV)‐ amid Th(NH2)4 zerfällt unterhalb 0° C spontan in A, das bei 25° in Th2(NH)3(NH2)2 (B) übergeht. Bei 100° C bildet sich hieraus Th(NH)2 (C) und weiter bei 130° C Th3N4 (D). Auch dieses Nitrid ist röntgenamorph (Flüssigkeitsdiagramm). A reagiert mit NH4J in flüssigem NH3 unter Bildung von Th(NH3)8J4; es reagiert also mit Ammono‐Säuren und Basen (Bildung der Amidosalze I, II und III; amphoteres Verhalten). Dem Amidosalz II kann durch Reaktion mit einer äquivalenten Menge NH4J alles Kalium entzogen werden. Das hierbei primär entstehende Th(NH2)4 zerfällt spontan unter NH3‐ Abspaltung; bei 25° C wird Dithorium‐triimido‐diamid (B) erhalten. Durch thermischen Abbau gehen II und III in I über; bei 270° C entsteht das Nitridosalz K3Th3N5 (IV). Bei 290–425° C zersetzt sich IV unter Bildung von röntgenamorphem ThN.
Formation of in vitro adducts between different classes of xenobiotics and the lysine-containing peptide Lys-Tyr was monitored by high-performance liquid chromatography and electrospray ionization mass spectrometry. The molecular structures of the main resulting products could be sensitively analyzed by mass spectrometry (flow injection analysis), enabling the detection of characteristic binding formations. Aldehydes such as formaldehyde, acetaldehyde, and benzaldehyde were shown to form stable linkages to lysine amino groups via Schiff bases. Other electrophilic substances (e.g., toluene-2,4-diisocyanate, 2,4-dinitro-1-fluorobenzene, 2,4,6-trinitrobenzene sulfonic acid, dansyl chloride, and phthalic acid anhydride) also formed covalent adducts with lysine residues. The reactivity of the compounds was quantified by measuring the amount of peptide that remained unchanged after incubation for a certain period with the xenobiotic. Although reactivity levels within this group of aldehydes varied only to a small extent, as would be expected, extreme differences were seen among the structurally heterogeneous group of nonaldehyde xenobiotics. These results support the hypothesis that simple chemical reactions may lead to the adduction of nucleophilic macromolecules such as peptides or proteins. Such reactions, in particular, Schiff base formation of aldehydes, have previously been shown to be capable of specifically interfering with costimulatory signaling on T cells. Our results suggest that electrophilic xenobiotics of other classes may also inherit the capacity to exert similar effects. Forming covalent linkage to peptides may represent a possible molecular mechanism of electrophilic xenobiotics in vivo, yielding immunotoxic effects. The model utilized in this study is appropriate for monitoring the adduction of xenobiotics to basic peptides and for analyzing the resulting molecular structures.
Most assays for drug screening are monitoring the metabolism of cells by detecting the NADH content, which symbolise its metabolic activity, indirectly. Nowadays, the performance of a LASER enables us to monitor the metabolic state of mammalian cells directly and on-line by using time-resolved autofluorescence detection. Therefore, we developed in combination with tissue engineering, an assay for monitoring minor toxic effects of volatile organic compounds (VOC), which are accused of inducing Sick Building Syndrome (SBS). Furthermore, we used the Laserfluoroscope (LF) for pharmacological studies on human bone marrow in vitro with special interest in chemotherapy simulation. In cancer research and therapy, the effect of chemostatica in vitro in the so-called oncobiogram is being tested ; up to now without great success. However, it showed among other things that tissue structure plays a vital role. Consequently, we succeeded in simulating a chemotherapy in vitro on human bone marrow. Furthermore, after tumor ektomy we were able to distinguish between tumoric and its surrounding healthy tissue by using the LF. With its sensitive detection of metabolic changes in tissues the LF enables a wide range of applications in biotechnology, e.g. for quality control in artificial organ engineering or biocompatability testing.
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