Novel intramolecular reactivity of oximes: synthesis of cyclic and spiro-fused imines

Under conventional heat (135-145 degrees C) or microwave irradiation and 1 equiv of acetic anhydride, ortho-substituted aryl-oximes undergo a novel sp3 C-H activated cyclization to produce the corresponding isoindoles, and aliphatic oximes afford the corresponding dihydropyrroles. The cyclization occurs with various substrates in good yield (46-82%) leading to unique spiro-fused and cyclic imines. An initial mechanistic investigation suggests the reaction occurs via a nitrenium or vinyl nitrene intermediate. [reaction: see text]     

CSF biomarker discovery using label-free nano-LC-MS based proteomic profiling: technical aspects

Biomarker discovery in cerebrospinal fluid (CSF) can provide important information helping to diagnose and monitor disease progression in brain disorders. We present a label-free LC-MS strategy to investigate the proteomic profile of CSF. We provide a framework and protocol addressing quality control, sample replication steps and the adaptation of pattern recognition methods for the detection of experimental variation and (most importantly) putative biomarkers. This strategy was tested using a total of 20 CSF samples (ten samples from healthy volunteers and ten from schizophrenia patients). A clear difference was found between healthy volunteers and schizophrenia patients. With technical and biological variation controlled, we were able to detect 77 proteins with confidence in CSF, of which seven were newly identified, without prior depletion of abundant protein species. Our strategy provides a simple and controlled method for CSF biomarker discovery.     

Synthesis of poly(para-phenylene)(2-isocyano-2-tosylpropane-1,3-diyl), poly(para-phenylene)(2-oxopropane-1,3-diyl) and oligo(cyclopentadienones) via carbonylative coupling of alpha,alpha'-dibromoxylene

Poly(para-phenylene)(2-oxopropane-1,3-diyl), a potential precursor of linear graphene, is generated in low yield from hydrolysis of a previously unknown poly(para-phenylene)(2-isocyano-2-tosylpropane-1,3-diyl) generated from inexpensive, commercially available starting materials.     

Iron arsenate frameworks

Six new iron arsenate framework structures, Fe(2)As(2)O(7) x 2H(2)O, [Fe(6)As(8)O(32)H(4)](2-)(1,4-butanediamininium(2+)) x 2H(2)O, [Fe(4)As(6)O(22)H(2)](2-)(piperazinium(2+)), [Fe(5)As(5)O(24)H(4)](2-)(piperazinium(2+)) x 2H(2)O, [Fe(6)As(7)O(31)H(5)](2-)(dabco(2+)) and LiFeAsO(4)OH have been synthesised under hydrothermal conditions. Incorporation of the amine cation templates leads to more open framework geometries and, in contrast to iron phosphates which have topologies based on PO(4) tetrahedra, the iron arsenate structures typically contain protonated As(O,OH)(4) units. The magnetic properties of the iron arsenates studied show Curie-Weiss behaviours with maxima in the chi(T) vs.T plots in the range 10-50 K.     

Structural, optical, and electrical properties of PbSe nanocrystal solids treated thermally or with simple amines

We describe the structural, optical, and electrical properties of films of spin-cast, oleate-capped PbSe nanocrystals that are treated thermally or chemically in solutions of hydrazine, methylamine, or pyridine to produce electronically coupled nanocrystal solids. Postdeposition heat treatments trigger nanocrystal sintering at approximately 200 degrees C, before a substantial fraction of the oleate capping group evaporates or pyrolyzes. The sintered nanocrystal films have a large hole density and are highly conductive. Most of the amine treatments preserve the size of the nanocrystals and remove much of the oleate, decreasing the separation between nanocrystals and yielding conductive films. X-ray scattering, X-ray photoelectron and optical spectroscopy, electron microscopy, and field-effect transistor electrical measurements are used to compare the impact of these chemical treatments. We find that the concentration of amines adsorbed to the NC films is very low in all cases. Treatments in hydrazine in acetonitrile remove only 2-7% of the oleate yet result in high-mobility n-type transistors. In contrast, ethanol-based hydrazine treatments remove 85-90% of the original oleate load. Treatments in pure ethanol strip 20% of the oleate and create conductive p-type transistors. Methylamine- and pyridine-treated films are also p-type. These chemically treated films oxidize rapidly in air to yield, after short air exposures, highly conductive p-type nanocrystal solids. Our results aid in the rational development of solar cells based on colloidal nanocrystal films.     

Floating lipid bilayers deposited on chemically grafted phosphatidylcholine surfaces

Floating supported bilayers (FSBs) are new systems which have emerged over the past few years to produce supported membrane mimics, where the bilayers remain associated with the substrate, but are cushioned from the substrates constraining influence by a large hydration layer. In this paper we describe a new approach to fabricating FSBs using a chemically grafted phospholipid layer as the support for the floating membrane. The grafted lipid layer was produced using a Langmuir-Schaeffer transfer of acryloyl-functionalized lipid onto a pre-prepared substrate, with AIBN-induced cross-polymerization to permanently bind the lipids in place. A bilayer of DSPC was then deposited onto this grafted monolayer using a combination of Langmuir-Blodgett and Langmuir-Schaeffer transfer. The resulting system was characterized by neutron reflection under two water contrasts, and we show that the new system shows a hydrating layer of approximately 17.5 A in the gel phase, which is comparable to previously described FSB systems. We provide evidence that the grafted substrate is reusable after cleaning and suggest that this greatly simplifies the fabrication and characterization of FSBs compared to previous methods.     

Autopiquer - a Robust and Reliable Peak Detection Algorithm for Mass Spectrometry

We present a simple algorithm for robust and unsupervised peak detection by determining a noise threshold in isotopically resolved mass spectrometry data. Solving this problem will greatly reduce the subjective and time-consuming manual picking of mass spectral peaks and so will prove beneficial in many research applications. The Autopiquer approach uses autocorrelation to test for the presence of (isotopic) structure in overlapping windows across the spectrum. Within each window, a noise threshold is optimized to remove the most unstructured data, whilst keeping as much of the (isotopic) structure as possible. This algorithm has been successfully demonstrated for both peak detection and spectral compression on data from many different classes of mass spectrometer and for different sample types, and this approach should also be extendible to other types of data that contain regularly spaced discrete peaks.

Open image in new window

Graphical Abstract ?

     

Realistic sampling of amino acid geometries for a multipolar polarizable force field

The Quantum Chemical Topological Force Field (QCTFF) uses the machine learning method kriging to map atomic multipole moments to the coordinates of all atoms in the molecular system. It is important that kriging operates on relevant and realistic training sets of molecular geometries. Therefore, we sampled single amino acid geometries directly from protein crystal structures stored in the Protein Databank (PDB). This sampling enhances the conformational realism (in terms of dihedral angles) of the training geometries. However, these geometries can be fraught with inaccurate bond lengths and valence angles due to artefacts of the refinement process of the X‐ray diffraction patterns, combined with experimentally invisible hydrogen atoms. This is why we developed a hybrid PDB/nonstationary normal modes (NM) sampling approach called PDB/NM. This method is superior over standard NM sampling, which captures only geometries optimized from the stationary points of single amino acids in the gas phase. Indeed, PDB/NM combines the sampling of relevant dihedral angles with chemically correct local geometries. Geometries sampled using PDB/NM were used to build kriging models for alanine and lysine, and their prediction accuracy was compared to models built from geometries sampled from three other sampling approaches. Bond length variation, as opposed to variation in dihedral angles, puts pressure on prediction accuracy, potentially lowering it. Hence, the larger coverage of dihedral angles of the PDB/NM method does not deteriorate the predictive accuracy of kriging models, compared to the NM sampling around local energetic minima used so far in the development of QCTFF. © 2015 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.     

Enhancement of electron-capture detection of methyl bromide in air by iodination.

An instrumentally simple and cost-effective method for the direct analysis of methyl bromide in ambient air is described. The method is based on the separation of sample components by gas chromatography, the conversion of methyl bromide to methyl iodide by reaction with an inorganic iodide salt, and the detection of the methyl iodide thereby produced by an electron-capture detector. Of the 20 different inorganic salts investigated here for conversion of methyl bromide to methyl iodide, zinc iodide was found to provide the greatest conversion efficiency. In addition, zinc iodide was found to provide high conversion efficiency at a modest reaction temperature, thereby minimizing both the thermal decomposition of compounds within the reaction volume and the level of column bleed introduced to the detector. The reactions of several other brominated and chlorinated organic compounds with zinc iodide have also been characterized. The successful application of this instrument to the quantitative determination of methyl bromide in a local background air sample is then demonstrated.