Umwandlung von 6-Methylen-tricyclo[3.2.1.02,7]oct-3-en-8-onen mit Ameisensäure in kernmethylierte Phenylessigsäuren

In a preceding communication [5] it was shown that 1, 5-dimethyl-6-methylene-tricyclo[3.2.1.0^2,7]oct-3-en-8-one ( 2 ) and related tricyclic ketones are converted by strong acids (CF₃COOH, FSO₃H) into polymethylated tropylium salts with loss of carbon monoxide, e.g. the 1, 2, 4-trimethyltropylium ion 4 from 2 (Scheme 1). Under the influence of neat formic acid at 20°, 2 gives rise to ring-methylated phenylacetic acids, i.e. 2, 4, 5-trimethylphenylacetic acid ( 5 , main product) as well as smaller amounts of 2, 4, 6-and 2, 3, 5-trimethylphenylacetic acids ( 6, 7 resp.; Scheme 2). –On rearrangement of 2 in HCOOD, ca. 2 D-atoms are incorporated (formula d₂-5) into the 2, 4, 5-trimethylphenylacetic acid. The tricyclic 15 , containing 3 methyl groups, gives 2, 3, 5, 6-tetramethylphenylacetic acid ( 11 ; Scheme 4) with formic acid; the isomeric tricyclic 16 , 2, 3, 4, 5-tetramethylphenylacetic acid ( 12 ; Scheme 5). From 1, 2, 4, 5-tetramethyl-6-methylene-tricyclo[3.2.1.0^2,7]oct-3-en-8-one ( 17 ) one obtains pentamethylphenylacetic acid ( 14 ; Scheme 6). Similarly from 18 , a phenylacetic acid derivative, most probably 4-ethyl-2, 5-dimethyl-phenylacetic acid ( 19 ; Scheme 17), has been obtained. –In no case was the formation of α-phenylpropionic acid derivatives observed, not even from the tricyclic 23 containing six methyl groups. From the tricyclic ketone 2 in 70% formic acid a trimethyl-cyclohepta-2, 4, 6-triene-1-carboxyclic acid with partial formula 24 , besides 2, 4, 5-trimethylphenylacetic acid ( 5 ), is formed. 24 remained practically unchanged on standing in neat formic acid and thus does not represent an intermediate product arising by the rearrangement of 2 in that solvent. On standing in methanolic sulfuric acid, tricyclic 2 furnishes the two stereioisomeric methanol-addition products Z- 26 and E- 26 (Scheme 10); these are converted into the phenylacetic acids 5 , 6 and 7 by neat formic acid. The conversion of 2 and related compounds into ring-polymethylated phenylacetic acids, represents a novel and rather complicated reaction. In our opinion the reaction paths represented in Schemes 12 and 18 are responsible for the conversion of 2 into the trimethylphenylacetic acids, compound 40 representing a key intermediate. Analogous reaction paths can be assumed for the other tricyclic ketone transformations. The use of shift reagents in the NMR. spectroscopy and the high-resolution gas-chromatography of the corresponding methyl esters proved particularly important for the analysis of the reaction mixtures. The majority of the polymethylated phenylacetic acids were independently synthesised by means of the Willgerodt-Kindler reaction (chap. 3.2.), whose course is strongly influenced by methyl groups in the ortho-positions of the acetophenone derivatives employed.     

An interpolation theorem for proper holomorphic embeddings

Given a Stein manifold x of dimension n > 1, a discrete sequence , and a discrete sequence where , there exists a proper holomorphic embedding satisfying f(a _j ) = b _j for every j = 1,2,... Forstnerič and Prezelj supported by grants P1-0291 and J1-6173, Republic of Slovenia. Kutzschebauch supported by Schweizerische National fonds grant 200021-107477/1. Ivarsson supported by The Wenner-Gren Foundations.     

Ultrahigh-resolution (1)H-(13)C HSQC spectra of metabolite mixtures using nonlinear sampling and forward maximum entropy reconstruction

To obtain a comprehensive assessment of metabolite levels from extracts of leukocytes, we have recorded ultrahigh-resolution 1H-13C HSQC NMR spectra of cell extracts, which exhibit spectral signatures of numerous small molecules. However, conventional acquisition of such spectra is time-consuming and hampers measurements on multiple samples, which would be needed for statistical analysis of metabolite concentrations. Here we show that the measurement time can be dramatically reduced without loss of spectral quality when using nonlinear sampling (NLS) and a new high-fidelity forward maximum-entropy (FM) reconstruction algorithm. This FM reconstruction conserves all measured time-domain data points and guesses the missing data points by an iterative process. This consists of discrete Fourier transformation of the sparse time-domain data set, computation of the spectral entropy, determination of a multidimensional entropy gradient, and calculation of new values for the missing time-domain data points with a conjugate gradient approach. Since this procedure does not alter measured data points, it reproduces signal intensities with high fidelity and does not suffer from a dynamic range problem. As an example we measured a natural abundance 1H-13C HSQC spectrum of metabolites from granulocyte cell extracts. We show that a high-resolution 1H-13C HSQC spectrum with 4k complex increments recorded linearly within 3.7 days can be reconstructed from one-seventh of the increments with nearly identical spectral appearance, indistinguishable signal intensities, and comparable or even lower root-mean-square (rms) and peak noise patterns measured in signal-free areas. Thus, this approach allows recording of ultrahigh resolution 1H-13C HSQC spectra in a fraction of the time needed for recording linearly sampled spectra.     

Measuring the coordination number and entropy of a 3D jammed emulsion packing by confocal microscopy

Jammed matter is by definition impenetrable to light, such that little is known about the geometry of jammed systems. Using confocal microscopy to image an emulsion in 3D, we first explain the origin of the enhanced fluorescence at the droplet contacts and then determine the contact network inside the model frictionless system. This enables the experimental determination of the average coordination number which agrees with the isostatic predicted value of approximately 6. Furthermore, we calculate the entropy of the packing from the network of contacts.     

Characterizing wood polymers in the primary cell wall of Norway spruce (<Emphasis Type="Italic">Picea abies</Emphasis> (L.) Karst.) using dynamic FT-IR spectroscopy

Dynamic Fourier Transform Infra-Red (FT-IR) spectroscopy was used to examine the interactions among cellulose, xyloglucan, pectin, protein and lignin in the outer fibre wall layers of spruce wood tracheids. Knowledge regarding these interactions is fundamental for understanding the fibre separation in a mechanical pulping process. Sheets made from an enriched primary cell wall material were used for studying the viscoelastic response of the polymers. The results indicated that strong interactions exist among lignin, protein, pectin, xyloglucan and cellulose in the primary cell wall. This signified a closely linked network structure of the components on the fibre surface. This ultrastructural arrangement in the primary cell wall and the relatively high content of lignin, pectin and protein in it, means that the primary cell wall is more submissive to selective chemical attacks, when compared to the secondary cell wall. A low ratio of cellulose Iα to cellulose Iβ in the primary cell wall was also found.     

Similar biological activities of two isostructural ruthenium and osmium complexes

In this study, we probe and verify the concept of designing unreactive bioactive metal complexes, in which the metal possesses a purely structural function, by investigating the consequences of replacing ruthenium in a bioactive half-sandwich kinase inhibitor scaffold by its heavier congener osmium. The two isostructural complexes are compared with respect to their anticancer properties in 1205 Lu melanoma cells, activation of the Wnt signaling pathway, IC(50) values against the protein kinases GSK-3beta and Pim-1, and binding modes to the protein kinase Pim-1 by protein crystallography. It was found that the two congeners display almost indistinguishable biological activities, which can be explained by their nearly identical three-dimensional structures and their identical mode of action as protein kinase inhibitors. This is a unique example in which the replacement of a metal in an anticancer scaffold by its heavier homologue does not alter its biological activity.     

Characterization of Mercury Contamination Surrounding a Chloralkali Production Facility in Tuzla,Bosnia and Herzegovina

Tuzla is among the most polluted cities of Bosnia and Herzegovina. The main source of pollution in the area is soil heavily contaminated by mercury released from a former chloralkali plant. This paper is focused on the characterization of mercury contaminated soil and air surrounding the chloralkali plant. In soil, the mobility and transformation of mercury were investigated by sequential extraction, while the methylation and reduction potentials were determined by the use of a radioactive tracer. Mercury emission from soil was determined by laboratory and by flux chamber measurements in the field. In addition, mercury concentrations in air were estimated by the analysis of air and the transplanted lichen Hypogymnia physodes. Mercury in soils in the vicinity of the chloralkali plant exceeded the background value by a factor of more than 3000. The fractionation of mercury in surface soil by sequential extraction showed that the mercury in soil was primarily bound to organic matter and a fraction containing elemental mercury and mercury (I) chloride is also significant. The obtained methylation and reduction potentials are low. The mercury flux from soil was estimated by two approaches. Fluxes of up to 8000?ng/m²/day were measured at the most polluted site; evaporation from soil was shown to be the primary source of elevated mercury in air. Air concentration mapping also revealed other sources of mercury; the most likely is the 715 MW coal power plant in the vicinity of former chloralkali facility.     

On the structural diversity of Shiga toxin glycosphingolipid receptors in lymphoid and myeloid cells determined by nanoelectrospray ionization tandem mass spectrometry

Shiga toxin (Stx, synonymous to verotoxin, VT) binds with high and low affinity to the globo‐series neutral glycosphingolipids (GSLs), globotriaosylceramide (Gb3Cer or Galα4Galβ4Glcβ1Cer, also known as CD77) and globotetraosylceramide (Gb4Cer or GalNAcβ3Galα4Galβ4Glcβ1Cer), respectively, which represent the targets of Stxs on many different cell types. B‐cell‐derived Raji cells and THP‐1 cells of monocytic origin are widely used for the investigation of Stx‐mediated cellular response, because Stx is known to cause cell death in both cell lines. Despite their functional importance, the Stx receptors of Raji and THP‐1 cells have so far not been investigated. This prompted us to explore the structures of their GSL receptors in detail by means of nanoelectrospray ionization quadrupole time‐of‐flight mass spectrometry (nanoESI‐QTOF‐MS) with collision‐induced dissociation (CID) in conjunction with Stx1 as well as anti‐Gb3Cer and anti‐Gb4Cer antibodies. Using the combination of a thin‐layer chromatography (TLC) overlay assay and MS¹ and MS² analysis we identified Gb3Cer (d18:1, C24:1/C24:0) as the prevalent Stx1‐receptor accompanied by less abundant Gb3Cer (d18:1, C16:0) in the neutral GSL fraction of Raji cells. The same Gb3Cer species but with almost equal proportions of the C24:1/C24:0 and C16:0 variants were found in THP‐1 cells. In addition, unusual hydroxylated Gb3Cer (d18:1, C24:1/C24:0) and Gb3Cer (d18:1, C26:1) could be identified in trace quantities in both cell lines. As the most obvious difference between Raji and THP‐1 cells we observed the expression of Gb4Cer in THP‐1 cells, whereas Raji cells failed to express this elongation product of Gb3Cer. Both short‐ and long‐chain fatty acid carrying Gb4Cer (d18:1, C16:0) and Gb4Cer (d18:1, C24:1/C24:0), respectively, were the prevalent Gb4Cer variants. This first report on the differential expression of Gb3Cer and Gb4Cer and their structural diversity in lymphoid and myeloid cell lines supports the hypothesis that such heterogeneities might play a functional role in the molecular assembly of GSLs in membrane organization and cellular signaling of Stx‐susceptible cells. Copyright © 2010 John Wiley & Sons, Ltd.