Search

Borata-alkenes can serve as anionic olefin equivalent ligands in transition metal chemistry. A chelate ligand of this type is described and used for metal coordination. Deprotonation of the Mes2P(CH2)2B(C6F5)2 frustrated Lewis pair in the α-CH[B] position gave the methylene-bridged phosphane/borata-alkene anion. It reacted with the [Rh(nbd)Cl] or [Rh(CO)2Cl] dimers to give the respective neutral chelate [P/C[double bond, length as m-dash]B][Rh] complexes. The reaction of the [P/C[double bond, length as m-dash]B]- anion with [Ir(cod)Cl]2 proceeded similarly, only that the complex underwent a subsequent oxidative addition reaction at the mesityl substituent. Both the resulting Ir(iii)hydride complex 15 and the P/borata-alkene Rh system 12 were used as hydrogenation catalysts. The [P/C[double bond, length as m-dash]B(C6F5)2]Rh(nbd) complex 12 served as a catalyst for arylacetylene polymerization.

The discrimination of d-galactosamine (G), representative of the amino-sugar class of compounds, has been probed through nano-ESI-FT-ICR mass spectrometry by isolating the relevant [C·H·G]+ proton-bound complexes with the enantiomers of the cyclochiral resorcin[4]arene C and allowing them to react toward three primary amines (B = EtNH2, iPrNH2, and (R)- and (S)-sBuNH2). The system under investigation presents several features that help to unveil the behavior of unprotected G in such a supramolecular architecture: (i) the hydrophobic derivatization of the C convex side forces the polar guest G to be coordinated by the cyclochiral concave region; (ii) protonated d-galactosamine exists as an anomeric mixture, dynamically interconverting throughout the experimental time-window; and (iii) different basicities of B allow the experiment to subtly tune the reactivity of the [C·H·G]+ complexes. Three [C·H·G]+ aggregate-types were found to exist, differing in both their origin and reactivity. The most reactive adducts ([C·H·G]ESI+), generated in the electrospray environment, undergo a G-to-B ligand exchange in competition with a partial isomerization to the unreactive [C·H·G]GAS+-type complexes. Finally, the poorly reactive [C·H·G]SOL+ aggregates are formed in solution over an hours-long time scale. A cyclochirality effect on the reactivity was found to depend on the considered [C·H·G]+ aggregate-type.

Organocatalysis has revolutionized asymmetric synthesis. However, the supramolecular interactions of organocatalysts in solution are often neglected, although the formation of catalyst aggregates can have a strong impact on the catalytic reaction. For phosphoric acid based organocatalysts, we have now established that catalyst–catalyst interactions can be suppressed by using macrocyclic catalysts, which react predominantly in a monomeric fashion, while they can be favored by integration into a bifunctional catenane, which reacts mainly as phosphoric acid dimers. For acyclic phosphoric acids, we found a strongly concentration dependent behavior, involving both monomeric and dimeric catalytic pathways. Based on a detailed experimental analysis, DFT-calculations and direct NMR-based observation of the catalyst aggregates, we could demonstrate that intermolecular acid–acid interactions have a drastic influence on the reaction rate and stereoselectivity of asymmetric transfer-hydrogenation catalyzed by chiral phosphoric acids., Supramolecular acid–acid interactions lead to competing monomeric and dimeric pathways in phosphoric acid catalysis – so that stereoselectivities depend on catalyst concentration.

Diastereoselective radical coupling was achieved with chiral auxiliaries. The radicals were generated by anodic decarboxylation of five malonic acid derivatives. These were prepared from benzyl malonates and four menthol auxiliaries. Coelectrolyses with 3,3-dimethylbutanoic acid in methanol at platinum electrodes in an undivided cell afforded hetero-coupling products in 22–69% yield with a diastereoselectivity ranging from 5 to 65% de. Electrolyses without a coacid led to diastereomeric homo-coupling products in 21–50% yield with ratios of diastereomers being 1.17:2.00:0.81 to 7.03:2.00. The stereochemistry of the new stereogenic centers was confirmed by X-ray structure analysis and 13C NMR data.

SummaryNeuronal information processing requires a large amount of energy, indicating that sugars and other metabolites must be efficiently delivered. However, reliable neuronal function also depends on the maintenance of a constant microenvironment in the brain. Therefore, neurons are efficiently separated from circulation by the blood-brain barrier, and their long axons are insulated by glial processes. At the example of the Drosophila brain, we addressed how sugar is shuttled across the barrier to nurture neurons. We show that glial cells of the blood-brain barrier specifically take up sugars and that their metabolism relies on glycolysis, which, surprisingly, is dispensable in neurons. Glial cells secrete alanine and lactate to fuel neuronal mitochondria, and lack of glial glycolysis specifically in the adult brain causes neurodegeneration. Our work implies that a global metabolic compartmentalization and coupling of neurons and glial cells is a conserved, fundamental feature of bilaterian nervous systems independent of their size.

The successive loss of two benzyl radicals from the [M + Na] + ions of the isomeric dihydroxybenzene dibenzyl ethers ( 2 – 4 ) and of the isomeric trihydroxybenzene tribenzyl ethers ( 5 – 7 ) under ESI/CID conditions has been studied by deuterium labelling, MS n experiments and DFT calculations. The fragmentation of the [M + Na] + ions of 2 and 4 consists exclusively of the consecutive losses of two C 7 H 7 (benzyl) radicals. This process is largely suppressed in the corresponding [M + Na] + ions of the meta isomer 3 and also in those of the 1,3,5-analog, phloroglucinol tribenzyl ether ( 6 ), suggesting the facile formation of sodiated ortho - and para -quinone ions, [C 6 H 4 O 2 + Na] + , in the cases of 2 and 4 , respectively. This finding is corroborated by a detailed investigation of the sodiated tribenzyl ethers of pyrogallol, [ 5 + Na] + , and 1,2,4-trihydroxybenzene, [ 7 + Na] + , and their isotopologs bearing differently labelled benzyl residues. Again, the successive loss of two C 7 H 7 radicals is the only fragmentation channel for ions [ 7 + Na] + and strongly predominates for ions [ 5 + Na] + , with the primary and secondary losses being highly regiospecific: ions [ 5 + Na] + lose the first benzyl residue almost exclusively from the central position ( O -2) and only then a lateral C 7 H 7 radical (from O -1 or O -3). Surprisingly, the very minor primary loss of a lateral benzyl group is followed by that of the other lateral one, suggesting a two-step isomerization process initiated by a 1,4-H shift. Ions [ 7 + Na] + lose the first benzyl radical almost exclusively from O -1, in very minor amounts from O -2 but not at all from O -4. The secondary loss of C 7 H 7 subsequent to the major primary loss occurs from both O -2 and O -4 in similar amounts, reflecting the relative stabilities of the sodiated benzyloxy-substituted ortho - and para -benzoquinones. This and several other details of the energy profiles associated with the twofold benzyl loss from ions [ 5 + Na] + and [ 7 + Na] + were calculated by use of the DFT methodology and were found to agree very well with the regioselectivities observed. Finally, the pyrogallol-based ions [ 5 + Na] + were found to eliminate benzaldehyde in minor but significant relative amounts, which takes place with high regioselectivity from O -1 or O -3.

The fragmentation reactions of the molecular ion of the three isomeric methylpyridines (2-picoline 1, 3-picoline 2, and 4-picoline 3) were studied using methods of tandem mass spectrometry and quantum chemical calculations with Gaussian-3 (G3) theory using the B3LYP density functional method (G3//B3LYP). Additionally RRKM calculations of the microcanonical rate constants of selected reaction pathways were performed. Derivatives of 2- and 4-picoline which bear an isotopically labeled methyl substituent (CD3: 1-d(3) and 3-d(3), (CH3)-C-13: 1-C-13 and 3-C-13) were also analyzed. Of the four primary dissociation reactions of the picoline radical cations 1(center dot+)-3(center dot+), the loss of a hydrogen atom, the elimination of an ethyne molecule and the elimination of a hydrogen cyanide molecule are observed in the MIKE spectra, while the loss of a methyl radical is only found in the collisional activation (CA) mass spectra of the molecular ions. The CA mass spectra of the labeled picoline radical ions reveal that some positional hydrogen exchange and carbon exchange takes place before the loss of the methyl radical. According to the G3 and RRKM calculations, the direct cleavage of the methyl substituent competes effectively with increasing internal energy of the ion with the loss of a methyl radical after rearrangements. The other three pathways found for metastable molecular ions are accompanied by efficient or complete hydrogen scrambling. The theoretical calculations prove that this scrambling occurs mainly by initial H-transfer from the methyl group to the pyridine ring and a subsequent H-ring walk. The calculations show further, that loss of H-center dot may occur from many of the intermediate ions after the rearrangements but that the direct loss of H-center dot from the methyl substituent competes successfully even at low energies, contrary to the behavior of the toluene radical ion. The elimination of an ethyne molecule gives rise to a broad flat-topped signal in the mass-analyzed ion kinetic energy (MIKE) spectra, and the MIKE spectra of 1-C-13 and 3-C-13 exhibit a 1:1 sharing of the C-13-label between ionic and neutral products. These particular features are explained by the theoretical calculations by a first rearrangement of the picoline radical cations to a seven-membered aza-cycloheptatriene radical cation 4(center dot+) followed by a rearrangement to a more rigid bicyclo-[3.2.0] isomer before the elimination of ethyne. Finally, the elimination of a hydrogen cyanide molecule exhibits only minor loss of C-13-label in the case of 1-C-13 and 3-C-13. This observation does not agree with any mechanism including a rearrangement to 4(center dot+). The theoretical calculations suggest that instead the loss of the hydrogen cyanide molecule proceeds by a cleavage of the pyridine ring after the initial H-transfer from the methyl substituent Although this pathway needs more energy than a rearrangement to 4(center dot+), its rate coefficients are superior owing to its loose transition states. (C) 2012 Elsevier B.V. All rights reserved.

A novel [2]catenane was synthesised by ring-closing metathesis from a Ca-bisphosphate template. The resulting interlocked structure features two chiral 1,1′-binaphthyl-phosphates, leading to a bifunctional catenane structure. Initial binding studies point at the applicability of such mechanically interlocked bisphosphates as artificial receptors for dicationic guest molecules.

An electron ionisation study on the fragmentation of metastable molecular radical cations of ethyl 3-phenylpropanoate (ethyl dihydrocinnamate) and related arylalkanoic acid esters was performed by mass-analysed ion kinetic energy (MIKE) spectrometry. Six deuterium-labelled isotopomers of ethyl dihydrocinnamate were synthesised and studied by MIKE spectrometry. The fragmentation leading to ions C7H7O+ (m/z 107) involving migration of the alkoxycarbonyl group was also observed in the 70-eV mass spectra of related alkyl dihydrocinnamates, but it was found to be a high-energy process that does not compete at low energies in metastable molecular ions. Instead, the metastable ions of ethyl dihydrocinnamate undergo competing losses of carbon monoxide, ethanol and the combined loss of these neutral fragments, giving ionised styrene, C8H8•+ (m/z 104). A highly specific H/D interchange involving the four hydrogen atoms at the benzylic α- and ortho-positions was found to precede the losses of ethanol and [ethanol + CO]. This represents another striking case of complete 4H – scrambling that enables the molecular ion to fully equilibrate the interchanging hydrogen atoms prior to fragmentation. A mechanism rationalising these observations and extending previously suggested mechanisms is proposed involving a series of distonic ions and the intermediacy of an ion/neutral complex. The metastable ions of the related esters exhibit in part similar fragmentation behaviour, but the McLafferty reaction turns out to be more favourable with higher alkyl dihydrocinnamates. For example, n-propyl 3-phenylpropanoate and isopropyl 3-phenylpropanoate react through highly distinct fragmentation channels.

N -Benzylpyridinium ions bearing an alkyl group at the pyridine nucleus were studied as potential precursors of gaseous ion/neutral complexes. The occurrence of I/N complexes [C 6 H 5 CH 2 + ··· alkylpyridine] was probed by the reactivity of the potential benzylic hydride donor sites present in the ortho- , meta- and para- alkyl groups (R = methyl, ethyl, isopropyl and benzyl). Collision-induced dissociation of the ions, carried out in an electrical ion cage mass spectrometer, revealed that hydride transfer strongly depends both on the energy requirements of the hydride transfer but also on the position of the hydride donor. Hydride transfer, giving rise to the loss of toluene, was found to occur exclusively with those N -benzylpyridinium ions which bear an isopropyl or a benzyl substituent in the ortho position of the pyridine ring, thus reflecting the intermediacy of I/N complexes. All of the putative hydride donor alkyl groups were found to be non-reactive in the meta and para positions, as were methyl and ethyl groups even in the ortho positions. Density functional calculations (B3LYP/6-311+G/3d,2p)//(B3LYP/6-31+G(d)) on the hydride-transfer and simple-cleavage channels were carried out to help rationalizing these observations. The results suggest that the intra-complex hydride abstraction from the 3- and 4-isopropyl- and from the 3- and 4-benzylpyridine neutrals, although being thermodynamically favorable, is suppressed by substantial intra-complex rotational (or reorientation) barriers.

Motivation: High-resolution mass spectrometry (MS) is among the most widely used technologies in metabolomics. Metabolites participate in almost all cellular processes, but most metabolites still remain uncharacterized. Determination of the sum formula is a crucial step in the identification of an unknown metabolite, as it reduces its possible structures to a hopefully manageable set. Results: We present a method for determining the sum formula of a metabolite solely from its mass and the natural distribution of its isotopes. Our input is a measured isotope pattern from a high resolution mass spectrometer, and we want to find those molecules that best match this pattern. Our method is computationally efficient, and results on experimental data are very promising: for orthogonal time-of-flight mass spectrometry, we correctly identify sum formulas for >90% of the molecules, ranging in mass up to 1000 Da. Availability: SIRIUS is available under the LGPL license at http://bio.informatik.uni-jena.de/sirius/ Contact: anton.pervukhin@minet.uni-jena.de Supplementary information: Supplementary data are available at Bioinformatics online.

O-linked oligosaccharide groups ranging from di- to hexasaccharide were beta-eliminated by mild alkaline treatment under reducting conditions from the peptidogalactomannan of Aspergillus fumigatus mycelial cell wall. The resulting reduced oligosaccharides, which were the minor components of the peptidogalactomannan fraction, were fractionated to homogeneity by successive gel filtration and high-performance liquid chromatography. Their primary structures were determined based on a combination of techniques including gas chromatography, ESI-QTOF-MS, H-1 COSY and TOCSY, and H-1-C-13 HMQC NMR spectroscopy and methylation analysis, to be: alpha-Glcp-(1 --> 6)-Man-ol, beta-Galf-(1 --> 6)-alpha-Manp-(1 --> 6)-Man-ol, beta-Galf-(1 --> 5)-beta-Galf-(1 --> 6)-alpha-Manp-(1 --> 6)-Man-ol and beta-Galf-(1 --> 5)-[beta-Galf-(1 --> 5](3)-beta-Galf-(1 --> 6)-Man-ol. The beta-Galf containing oligosaccharides have not been previously described as fungal O-linked oligosaccharides. The peptidogalactomannan is antigenic and was recognized by human sera of patients with aspergillosis when probed by ELISA, but de-O-glycosylation rendered a 50% decrease in its reactivity. Furthermore, when tested in a hapten inhibition test, the isolated oligosaccharide alditols were able to block, on a dose-response basis, recognition between human sera and the intact peptidogalactomannan. The immunodominant epitopes were present in the tetra- and hexasaccharide, which contain a beta-Galf-(1 --> 5)-beta-Galf terminal group. These results suggest that the O-glycosidically linked oligosaccharide chains, despite being the less abundant carbohydrate component of the A. fumigatus peptidogalactomannan, may account for a significant part of its antigenicity, other than the known activity associated with the galactomannan component.

This review describes the state-of-art in the field of the gas-phase reactivity of diastereomeric complexes formed between a chiral artificial receptor and a biologically active molecule. The presented experimental approach is a ligand-displacement reaction carried out in a nano ESI-FT-ICR instrument, supported by a thermodynamic MS-study and molecular-mechanics and molecular-dynamics (MM/MD) computational techniques. The noncovalent ion–molecule complexes are ideal for the study of chiral recognition in the absence of complicating solvent and counterion effects.

The gas-phase encounters between 2-aminobutane and proton-bound chiral resorcin[4]arene/nucleoside complexes behave in the gas phase as supramolecular "chiroselective logic gates" by releasing the nucleoside depending on the resorcin[4] arene and the 2-aminobutane configurations.

The stereoselectivity of the reaction between (R)-(-)-2-butylamine and the diastereomeric proton-bound complexes of (+)-catharanthine (C) or (-)-vindoline (V) with some chiral amido[4]resorcinarenes has been investigated in the gas phase by ESI-FT-ICR-MS. The reaction stereoselectivity (0.56 < k(homo)/k(hetero) < 16.9) is found to depend critically on the functional groups present in the chiral pendants of the hosts. Rationalisation of the kinetic results is based on careful computational and spectroscopic studies of the most stable conformations of (+)-catharanthine and its protonated form in the isolated state and in water, as well as in a representative host structure. The emerging picture points to the relevant diastereomeric proton-bound complexes as quasi-degenerate, thus suggesting that their stereoselectivity in the guest exchange reaction is mostly due to kinetic factors. The results of this study may represent a starting point for a deeper comprehension of the intrinsic factors that endow these molecules, and their dimeric forms, with their biochemical properties.

The displacement processes of several guests, incorporated in a calixarene host system, were investigated in the gas phase by electrospray ionization-Fourier transform-ion cyclotron resonance (ESI-FT-ICR) mass spectrometry. The complexes resulting from a resorcin[4]arene host with ammonia and sec-butylamine guests were isolated in an ICR-cell, separately using both states of the photos-witch as well as two reference systems for the open and closed forms of the photoswitchable host. The isolated complexes were forced to exchange the guest by using methylamine, ethylamine and sec-butylamine, resulting in different reaction rates for all the measured systems. Especially, the reaction rates of both states of the photoswitch are dependent on the provided guest. Potential side effects like proton exchanges were examined by an H/D-exchange experiment. The results were investigated and supported by quantum chemical calculations (DFT). Copyright (C) 2008 John Wiley & Sons, Ltd.

On the research avenue opened by the rigidified double-spanned resorcin[4]arene 1, we have synthesized both enantiomers of the two chiral basket resorcin[4]arenes 3 and 4, each containing two 1,2-diaminocyclohexane and 1,2-diphenylethylenediamine bridges, respectively. In the new compounds, the aromatic rims assume the expected flattened cone arrangement, whereas two different conformations, tentatively designated as "open wings" and "folded wings", were attributed to the bridge substituents according to molecular modeling studies. In MSn (ESI) experiments, the proton-bonded diastereomeric [4.H.A](+) complexes with amino acidic guests (A) exhibited a pronounced selectivity towards the enantiomers of tyrosine methyl ester (tyr(OMe)) and amphetamine (amph), whereas the chirality of tryptophan (trp) was ineffective. Moreover, a kinetic study on the base-induced displacement of the guest revealed that the L-tyr(OMe) (and L-amph) enantiomer is faster displaced from the heterochiral [4.H.L-tyr(OMe)](+) (or [ent-4.H.L-amph](+)) complex than from the homochiral [ent-4.H.L-tyr(OMe)](+) (or [4.H.L-amph](+)) one. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007.

Phytochemical investigation of the stem bark of Lonchocarpus laxiflorus yielded three new cassane diterpenoids, lonchocassane A [cassa-13 (14), 15-dien-18, 20-dioic acid], lonchocassane B [cassa-13 (14), 15-dien-20-oxo-18-oic acid] and lonchocassane C [cassa-13 (14), 15-dien-20-carboxyl-18-methylcarboxylate]. The known compounds betulinic acid, betulinic acid acetate, betulin, lupeol, lupenone, trilinoleate, hexacosanyl and triacontanyl caffeates, 4-hydroxy-4-methylpentan-2-one, β-sitosterol, β-sitosterol acetate and stigmasterol were also isolated. The structures and identities of the compounds were established by spectroscopic methods.

The serpin gene Spn4 from Drosophila melanogaster encodes multiple isoforms with alternative reactive site loops (RSL). Here, we show that isoform Spn4A inhibits human furin with an apparent k(assoc) of 5.5 x 10(6) M-1 s(-1). The serpin forms SDS-stable complexes with the enzyme and the RSL of Spn4A is cleaved C-terminally to the sequence -Arg-Arg-Lys-Argdown arrow in accord with the recognition/cleavage site of furin. Immunofluorescence studies show that Spn4A is localized in the endoplasmic reticulum (ER), suggesting that the inhibitor is an interesting tool for investigating the cellular mechanisms regulating furin and for the design of agents controlling prohormone convertases. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.