The application of "click chemistry" for the decoration of 2(1H)-pyrazinone scaffold: generation of templates

The "click chemistry" approach has been explored on the 2-(1H)-pyrazinone scaffold for the generation of pharmacologically interesting heterocyclic moieties. Huisgen 1,3-dipolar cycloaddition has been evaluated as the key step for the construction of the 1,2,3-triazole ring at the C-3 position of 2-(1H)-pyrazinones. Two different pathways have been successfully evaluated: (1) via C-C or C-O linkage of the acetylenic part to the C-3 position of the 2-(1H)-pyrazinone scaffold or (2) via azide introduction in the C-3 position. The subsequent application of "click chemistry" resulted in the formation of hitherto unknown skeletons. Microwave irradiation has successfully been applied in different steps of the sequence.     

Changes in calmodulin main-chain dynamics upon ligand binding revealed by cross-correlated NMR relaxation measurements

The fast dynamics of protein backbones are often investigated by nuclear magnetic relaxation experiments that report on the degree of spatial restriction of the amide bond vector. By comparing calmodulin in the peptide-bound and peptide-free states with these classical methods, we observe little difference in the dynamics of the polypeptide main chain (average order parameter decrease of 0.01 unit upon binding). However, when using NMR methods that monitor the mobility of the CO-Calpha bond vector, we reveal a significant reduction of dynamics of the protein main chain (average order parameter decrease of 0.048 units). Previous investigations have suggested that the side-chain dynamics is reduced by an average of 0.07 order parameter units upon ligand binding (Lee, A. L.; Kinnear, S. A.; Wand, A. J. Nat. Struct. Biol. 2000, 7, 72-77). The current findings suggest that the change of the CO-Calpha bond vector dynamics is intermediate between the changes in NH and side-chain dynamics and report a previously undetected loss of main-chain entropy. Weak site-to-site correlations between the different motional indicators are also observed.     

Protein-reactive natural products

Researchers in the post-genome era are confronted with the daunting task of assigning structure and function to tens of thousands of encoded proteins. To realize this goal, new technologies are emerging for the analysis of protein function on a global scale, such as activity-based protein profiling (ABPP), which aims to develop active site-directed chemical probes for enzyme analysis in whole proteomes. For the pursuit of such chemical proteomic technologies, it is helpful to derive inspiration from protein-reactive natural products. Natural products use a remarkably diverse set of mechanisms to covalently modify enzymes from distinct mechanistic classes, thus providing a wellspring of chemical concepts that can be exploited for the design of active-site-directed proteomic probes. Herein, we highlight several examples of protein-reactive natural products and illustrate how their mechanisms of action have influenced and continue to shape the progression of chemical proteomic technologies like ABPP.     

The Electronic Structure of Azuleno[1,2,3-cd]phenalene and Azuleno[5,6,7-cd]phenalene,a Comparison

The photoelectron (PE.) spectra of azuleno[l, 2, 3-cd]phenalene ( 1 ) and azuleno- [5,6,7-cd]phenalene( 2 ) have been recorded. The first five bands of both compounds could be assigned to transitions corresponding to removal of electrons from 4a₂, 6b₁, 5b₁, 3a₂ and 4b_l orbitals. This assignment is based mainly on a comparison between the observed ionization potentials and orbital energies calculated in a HMO and a PPP model. The UV./VIS. polarized absorption spectrum of 1 in the region 10000–45000 cm^?1 has been measured by means of the stretched film technique. The measurements were performed in polyethylene sheets at 77°K. Several bands could be assigned to π* ← π transitions calculated by a PPP-CI method. A comparison between the electronic structures of 1 and 2 is made by means of a simple HMO diagram.     

Determination of manganese and zinc in powdered chocolate samples by slurry sampling using sequential multi-element flame atomic absorption spectrometry

In the present work, a slurry sampling flame atomic absorption spectrometric method to determine directly manganese and zinc in powdered chocolate samples is proposed. The optimization step was performed using univariate methodology involving the following factors: nature and concentration of the acid solution, sonication time, and particle size. The established conditions led to the use of a sample mass of 150 mg, 2.0 mol L^− 1 nitric acid solution, sonication time of 15 min, and a slurry volume of 50 mL. This method allows the determination of manganese and zinc with detection limit of 52 and 61 ng g^− 1, respectively, and a precision expressed as relative standard deviation (RSD) of 2.6% and 3.2% (both, n = 10) for contents of manganese and zinc of 52.4 and 100.0 μg g^− 1, respectively. The proposed method was applied for determination of manganese and zinc in five powdered chocolate samples. In these, the manganese content varied from 42.8 to 52.7 and from 88.6 to 102.4 μg g^− 1 of zinc. The analytical results were compared with the results obtained by analysis of these samples after digestion using open vessel and acid bomb digestion procedures and determination using FS-FAAS. The statistical comparison by t-test (95% confidence level) showed no significant difference between these results.     

Influence of promoters on the performance of Au/MnOx and Pt/SnOx/SiO2 low-temperature CO oxidation catalysts

The influence of promoters on Pt/SnO_x/SiO₂ and Au/MnO_x low-temperature CO oxidation catalysts has been investigated under stoichiometric reaction conditions with no CO₂ added to the feed gas. The performance of Pt/SnO_x/SiO₂ catalysts is improved significantly by the addition of 1 wt.% Fe but reduced by the addition of 5 wt.%Fe, 1 wt.% Sb, 5 wt.% Sb, 1 wt.% As, 5 wt.%As and 1.8 wt.% P. The performance of Au/MnO_x is improved significantly by the addition of 1 at.% Ce but reduced by the addition of 1 at.% Co. For the catalysts and conditions examined, the Au/MnO_x catalysts are superior to the Pt/SnO_x/SiO₂ catalysts with respect to both activity and decay characteristics.     

Ermittlung der Zusammensetzung von Niederschl?gen nach der Methode der kontinuierlichen Variationen

Zusammenfassung Die Methode der kontinuierlichen Variationen nach OstromisslensKy-JOB lÄ\t sich mit sehr gutem Erfolg zur Ermittlung der Zusammensetzung von Verbindungen heranziehen, die sich beim Zusammengie\en von Lösungen als Niederschlag bilden. Im Gegensatz zu Komplexen in Lösungen, bei denen in der Praxis nur einfache Zusammensetzungen vorkommen und daher für x _max in der Regel nur die Werte 0,50, 0,67 und eventuell 0,75 auftreten, können bei NiederschlÄgen für die Abszisse des Maximums der Job-Kurve auch zahlreiche von den genannten Zahlen abweichende Werte reell beobachtet werden.

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Summary The method of continuous variations according to Ostromisslensky Job can be successfully employed for the determination of the composition of precipitates formed by mixing of solutions. With complexes in solutions only simple compositions are encountered and generally only the values 0.50, 0.67, and possibly 0.75 are found for the abscissa of the maximum of the Job curve. In contrast to that numerous deviations from these values are observed in case of precipitates.

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Für die Durchführung dieser Arbeit wurden dankenswerterweise Forschungsmittel aus dem ERP-Sondervermögen bereitgestellt. — Dem Verbande der Chemischen Industrie und der Deutschen Forschungsgemeinschaft, die diese Arbeit unterstützt haben, danken wir bestens.     

Empfindliche Methode zur Bestimmung geringer Schwefelgehalte in Wolframoxiden und Wolframpulvern

Zusammenfassung Der Schwefel in Wolframoxiden und Wolframpulvern wird im Wasserstoffstrom bei 800°C in H₂S übergeführt, der in Cadmium-Zinkacetat-Lösung absorbiert und anschließend jodometrisch titriert wird. Die Anwesenheit von WO₃ ermöglicht eine quantitative Umwandlung von Sulfatschwefel in H₂S. Die Standardabweichung beträgt für ein Wolframoxid mit 310 ppm S±13 ppmS und für ein Wolfram-Metallpulver mit 45 ppm S±1 ppm S.

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Sulfur is converted into hydrogen sulphide by hydrogenation at 800°C. This H₂S is absorbed in a cadmium-zinc acetate solution and titrated iodometrically. The presence of WO₃ makes possible a quantitative conversion of sulphate sulphur into H₂S. The standard deviation is ±13 ppm S for WO₃ containing 310 ppm S, and ±1 ppm S for metallic tungsten powder containing 45 ppm S.

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Herrn Prof. Dr.E. Hayek zum 60. Geburtstag gewidmet.