Local Inflammation Precedes Diaphragm Wasting and Fibrotic Remodelling in a Mouse Model of Pancreatic Cancer.

Background: Cancer cachexia represents a debilitating muscle wasting condition that is highly prevalent in gastrointestinal cancers, including pancreatic ductal adenocarcinoma (PDAC). Cachexia is estimated to contribute to ~30% of cancer-related deaths, with deterioration of respiratory muscles suspected to be a key contributor to cachexia-associated morbidity and mortality. In recent studies, we identified fibrotic remodelling of respiratory accessory muscles as a key feature of human PDAC cachexia.

Adducts of Lewis acidic stibanes with phosphane chalcogenides.

Starting from ClSbR (R = CF, 3,5-(CF)CH) and H(E)P(Bu) (E = O, S), we prepared the oxy- and sulphanediyl-bridged adducts RSb(Cl)-E-(H)P(Bu), which are stable against the elimination of HCl. The different electron-withdrawing substituents and chalcogen bridging units influence the size of the Sb-E-P angle. ClSb(CF) and BuSnH react to give HSb(CF), which seems to interact weakly with H(O)P(Bu) in solution as observed NMR.

A geminal antimony(iii)/phosphorus(iii) frustrated Lewis pair.

The geminal Lewis pair (FC)SbCHP(Bu) (1) was prepared by reacting (FC)SbCl with LiCHP(Bu). Despite its extremely electronegative pentafluoroethyl substituents, the neutral 1 exhibits a relatively soft acidic antimony function according to the HSAB concept (hard-soft acid-base). These properties lead to a reversibility in the binding of CS to 1, as observed by VT-NMR spectroscopy, while no reaction with CO is observed.

The Perfluoro-o-phenylene-mercury Trimer [Hg(o-CF)] - a Textbook Example of Phase-Dependent Structural Differences.

The geometric and electronic structure of [Hg(o-CF)] (1) in the gas phase, i. e. free of intermolecular interactions, was determined by a synchronous gas-phase electron diffraction/mass spectrometry experiment (GED/MS), complemented by quantum chemical calculations.

Tridentate Lewis Acids Based on Tribenzotriquinacene Chalices.

Chalice-shaped tridentate poly-Lewis acids (PLA) based on the tribenzotriquinacene (TBTQ) scaffold have been synthesised. Stannylation of the alkyne units, attached via phenyl-spacers to the benzhydrylic positions to the TBTQ scaffold, with MeNSnMe afforded the trimethyltin substituted TBTQ derivative. Replacement of these tin functions with other elements resulted in rigid boron- and aluminium-functionalised PLAs.

Bidentate boron Lewis acids: synthesis by tin boron exchange reaction and host-guest complex formation.

Four bidentate boron Lewis acids based on the 1,8-diethynylanthracene backbone have been synthesized by a tin-boron exchange reaction with various chloroboranes, yielding the products in good to excellent yields. Complexation experiments of the host compounds with pyridine, pyrimidine and TMEDA demonstrated striking differences in terms of formation and solubility of the supramolecular adducts. The host-guest complexes were investigated by multinuclear NMR spectroscopy and structurally characterized by X-ray diffraction experiments, illustrating the adaptation of the host system upon adduct formation with different neutral guest molecules.

Hexadentate poly-Lewis acids based on the bowl-shaped tribenzotriquinacene.

Hexadentate poly-Lewis acids (PLA) based on the bowl-shaped tribenzotriquinacene (TBTQ) have been synthesised. The introduction of three -propyl groups into the benzhydrylic positions of the TBTQ backbone has significantly increased the solubility of the subsequently derived compounds. Semi-flexible PLAs containing boron and aluminium were obtained by hydrometallation of the corresponding 2,3,6,7,10,11-hexaalkynyl-TBTQ.

Phase-Dependence of Molecular Structures Arising from Weak London Dispersion Interactions.

ConspectusThe structures of molecules can be different in different phases. Intermolecular forces, even those of weak noncovalent interactions (WNCIs), can lead to a preference for quite different conformations in the solid, the gas, and the liquid phases. WNCIs can cause variations in bond lengths, angles, and torsional angles.

Mitochondrial uncouplers impair human sperm motility without altering ATP content†.

In human spermatozoa, the electrochemical potentials across the mitochondrial and plasma membranes are related to sperm functionality and fertility, but the exact role of each potential has yet to be clarified. Impairing sperm mitochondrial function has been considered as an approach to creating male or unisex contraceptives, but it has yet to be shown whether this approach would ultimately block the ability of sperm to reach or fertilize an egg. To investigate whether the mitochondrial and plasma membrane potentials are necessary for sperm fertility, human sperm were treated with two small-molecule mitochondrial uncouplers (niclosamide ethanolamine and BAM15) that depolarize membranes by inducing passive proton flow, and evaluated the effects on a variety of sperm physiological processes.

Accurate single crystal and gas-phase molecular structures of acenaphthene: a starting point in the search for the longest C-C bond.

The molecular structure of acenaphthene has been determined experimentally in the gas phase using gas electron diffraction intensities and literature-available rotational constants. Supplementary high-level quantum-chemical calculations were utilized in refinements of the semi-empirical equilibrium structure. In this work we investigate on how different schemes of GED data averaging and weighting can be used for obtaining the most accurate and precise structural parameters.

Gas-phase equilibrium molecular structures and thermochemistry of anthracene and rubrene.

Semi-experimental gas-phase structures of anthracene and rubrene (5,6,11,12-tetraphenyltetracene) were determined by means of gas electron diffraction (GED). The use of the flexible restraints in the refinement of the GED data successfully resolves non-equivalent C-C bond lengths. The tetracene core of an isolated rubrene molecule was found to exhibit a twist distortion of about 18°; this is less than DFT calculations predict (30-40°).

Synthesis of bi- and tetradentate poly-Lewis acids by hydroalumination of poly-alkynyl-anthracene derivatives.

Photo-dimers of 1,5-diethynylanthracene and 1,5-bis[(trimethylsilyl)ethynyl]anthracene, obtained by UV radiation of the monomers, were treated with the bulky aluminium hydride [(SiMe)HC]AlH in hydroalumination reactions. Hydroalumination of the tetraethynyl-substituted anthracene photo-dimers ( and ) led to fourfold aluminium-functionalized Janus-like products with two aluminium functions on each side oriented towards the same direction. The reactions of the monomeric anthracene derivatives with [(SiMe)HC]AlH afforded semi-flexible bidentate Lewis acids, which are interesting building blocks for molecular chains bearing multiple Lewis-acidic functions.

Host-guest chemistry of a bidentate silyl-triflate bis-Lewis acid - complex complexation behaviour unravelled by diffusion NMR spectroscopy.

The bidentate silicon-based Lewis acid, bis(dimethyl-(trifluoromethylsulfonyl)silylethyl)dimethylsilane, MeSi[(CH)SiMeOTf], was prepared in a two-step synthesis starting from dimethyldivinylsilane by hydrosilylation with dimethylchlorosilane and subsequent Lewis acidity enhancement of the terminal silicon atoms by substituting the chlorine with triflate groups using silver triflate. The potential of the resulting MeSi[(CH)SiMeOTf] for binding of Lewis basic guests was explored in reactions with mono- and bifunctional aromatic nitrogen bases. A 1 : 2-adduct with pyridine and a 2 : 2-adduct with 4,4'-bipyridine was structurally characterised in the solid state.

Monitoring dynamic pre-crystallization aggregation processes in solution by VT-DOSY-NMR spectroscopy.

Equimolar mixtures of pyridine (Py) with -halotetrafluoropyridine (BrTFP and ITFP) were investigated by VT-diffusion NMR experiments. The formation of a halogen-bond-stabilized ITFPPy complex was detected upon cooling a solution in methylcyclohexane- to 260 K; this allows monitoring a halogen-bond-driven aggregation process preceding crystallization in solution.

The Structure of Bis(catecholato)silanes: Phase Adaptation by Dynamic Covalent Chemistry of the Si-O Bond.

Catechols occupy a unique role in the structural, bio-, and geochemistry of silicon. Although a wealth of knowledge exists on their hypercoordinate complexes, the structure of tetracoordinate bis(catecholato)silane, Si(cat) , has been enigmatic since its first report in 1951. Indeed, the claim of a planar-tetracoordinated silicon in triggered a prominent debate, which is unsettled to this day.

Bidentate Lewis Acids Derived from o-Diethynylbenzene with Group 13 and 14 Functions.

Starting from 1,2-diethynylbenzene, a series of bidentate Lewis acids was prepared by means of hydrometalations, in particular hydrosilylation, hydroboration, hydroalumination and terminal metalation based on group 13 and 14 elements. In the case of terminal alkyne metalation, the Lewis-acidic gallium function was introduced using triethylgallium under alkane elimination. A total of six different Lewis acids based on a semiflexible organic scaffold were prepared, bearing -SiClMe , -SiCl Me, -SiCl , -B(C F ) , -AlBis (Bis=bis(trimethylsilyl)methyl) and -GaEt as the corresponding functional units.

Hydrogen-bond-induced selectivity of a head-to-head photo-dimerisation of dialkynylanthracene - access to tetradentate Lewis acids.

Using 2-hydroxypropyl-protecting groups, 1,8-dialkynylanthracene photo-dimers were prepared in head-to-head-configuration by UV irradiation on a multi-gram scale. In non-polar solvents, the combination of non-covalent hydrogen bonds and π-π-interactions induces the formation of the -isomer in up to 85% yield. Instead, more polar solvents or irradiation of unprotected 1,8-diethynylanthracene led to formation of the corresponding -isomer in large excess.

Fever Burden in Patients With Subarachnoid Hemorrhage and the Increased Use of Antibiotics.

Background: Fever occurs in the majority of subarachnoid hemorrhage (SAH) patients. Nearly 50% of SAH patients have noninfectious fevers. Data are lacking describing the effects of fever burden in the SAH patient population.

Halogen Bonds of Halotetrafluoropyridines in Crystals and Co-crystals with Benzene and Pyridine.

The structures of the three para-substituted halotetrafluoropyridines with chlorine, bromine, and iodine have been determined in the solid state (X-ray diffraction). The structures of these compounds and that of pentafluoropyridine were also determined in the gas phase (electron diffraction). Structures in the solid state of the bromine and iodine derivatives exhibit halogen bonding as a structure-determining motif.

A Rational Approach to Tetra-Functional Photo-Switches.

α,ω-Bis(1,8-dichloroanthracen-10-yl)alkanes with (CH) -linker units (=1-4) were synthesized starting from 1,8-dichloroanthracen-10(9)-one. This was transformed into anthracenes with allyl, bromomethyl and propargyl substituents in position 10; these were converted in various C-C-bond formation reactions (plus hydrogenation), leading to two anthracene units flexibly linked by α,ω-alkandiyl groups. 1,2-Ethandiyl- and 1,3-propandiyl-linked derivatives were functionalized with ethynyl groups in positions 1, 8, 1' and 8', and these terminally functionalized by MeSn groups using MeNSnMe.

Peripheral nerve grafts implanted into the substantia nigra in patients with Parkinson's disease during deep brain stimulation surgery: 1-year follow-up study of safety, feasibility, and clinical outcome.

OBJECTIVECurrently, there is no treatment that slows or halts the progression of Parkinson's disease. Delivery of various neurotrophic factors to restore dopaminergic function has become a focus of study in an effort to fill this unmet need for patients with Parkinson's disease. Schwann cells provide a readily available source of such factors.

Regiochemical Control in Triptycene Formation-An Exercise in Subtle Balancing Multiple Factors.

Reactions between 1,8-dichloroanthracenes with substituents in position 10 and -chloroaryne afford mixtures of 1,8,13- () and 1,8,16-trichlorotriptycenes (). The / ratio is dependent on these substituents. Electropositive substituents like SiMe and GeMe lead to preferred formation of the -isomer, whereas CMe groups exclusively afford the -isomer.

Facile routes to abnormal-NHC-cobalt(ii) complexes.

Deprotonation of [IPr]I (1) with Co{N(SiMe)} readily affords the abnormal N-heterocyclic carbene (aNHC) complex (aIPr)CoI (2) (aIPr = 1,3-bis(2,6-iPrCH)-2-phenyl-imidazol-4-ylidene). Treatment of 1 with NaHBEt yields (aIPr)BEt (3) that serves as an aNHC-transfer agent and yields (aIPr)Co{N(SiMe)} (4) on reaction with Co{N(SiMe)}.

Gas-phase structure of 1,8-bis[(trimethylsilyl)ethynyl]anthracene: cog-wheel-type vs. independent internal rotation and influence of dispersion interactions.

The gas-phase structure of 1,8-bis[(trimethylsilyl)ethynyl]anthracene (1,8-BTMSA) was determined by a combined gas electron diffraction (GED)/mass spectrometry (MS) experiment as well as by quantum-chemical calculations (QC). DFT and dispersion corrected DFT calculations (DFT-D3) predicted two slightly different structures for 1,8-BTMSA concerning the mutual orientation of the two -C-C[triple bond, length as m-dash]C-SiMe units: away from one another or both bent to the same side. An attempt was made to distinguish these structures by GED structural analysis.