Vinylic MIDA Boronates: New Building Blocks for the Synthesis of Aza‐Heterocycles

A two‐step synthesis of structurally diverse pyrrole‐containing bicyclic systems is reported. ortho‐Nitro‐haloarenes coupled with vinylic N‐methyliminodiacetic acid (MIDA) boronates generate ortho‐vinyl‐nitroarenes, which undergo a “metal‐free” nitrene insertion, resulting in a new pyrrole ring. This novel synthetic approach has a wide substrate tolerance and it is applicable in the preparation of more complex “drug‐like” molecules. Interestingly, an ortho‐nitro‐allylarene derivative furnished a cyclic β‐aminophosphonate motif.     

Altered extracellular striatal in vivo biotransformation of the opioid neuropeptide dynorphin A(1-17) in the unilateral 6-OHDA rat model of Parkinson's disease

The in vivo biotransformation of dynorphin A(1-17) (Dyn A) was studied in the striatum of hemiparkinsonian rats by using microdialysis in combination with nanoflow reversed-phase liquid chromatography/electrospray time-of-flight mass spectrometry. The microdialysis probes were implanted into both hemispheres of unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats. Dyn A (10 pmol microl(-1)) was infused through the probes at 0.4 microl min(-1) for 2 h. Samples were collected every 30 min and analyzed by mass spectrometry. The results showed for the first time that there was a difference in the Dyn A biotransformation when comparing the two corresponding sides of the brain. Dyn A metabolites 1-8, 1-16, 5-17, 10-17, 7-10 and 8-10 were detected in the dopamine-depleted striatum but not in the untreated striatum. Dyn A biotransformed fragments found in both hemispheres were N-terminal fragments 1-4, 1-5, 1-6, 1-11, 1-12 and 1-13, C-terminal fragments 2-17, 3-17, 4-17, 7-17 and 8-17 and internal fragments 2-5, 2-10, 2-11, 2-12, and 8-15. The relative levels of these fragments were lower in the dopamine-depleted striatum. The results imply that the extracellular in vivo processing of the dynorphin system is being disturbed in the 6-OHDA-lesion animal model of Parkinson's disease.     

On-line SFE-GC for determination of PCBs in human milk and blood serum

On-line coupled supercritical fluid extraction and gas chromatography (SFE-GC) has been utilized for the determination of PCBs and other organochlorine compounds in human milk and blood serum. The procedure involved preconcentration of the sample on C₁₈-silica sorbent in an extraction cell: after precipitation of the proteins up to 20 ml of human milk was concentrated on 0.5 g of sorbent. Serum (up to 5 ml) was applied to the C₁₈ material without pretreatment. Basic alumina was utilized as a selective adsorbent for lipids in the on-line SFE-GC system. The method was used to analyze milk and serum spiked with 0.5 and 10 ng of Aroclor 1260 and the results compared with those obtained by liquid–liquid extraction of serum.     

Access to the Bis‐benzene Cobalt(I) Sandwich Cation and its Derivatives: Synthons for a “Naked” Cobalt(I) Source?

The synthesis and structural characterization of the hitherto unknown parent Co(bz)₂⁺ (bz=benzene) complex and several of its derivatives are described. Their synthesis starts either from a CoCO₅⁺ salt, or directly from Co₂(CO)₈ and a Ag⁺ salt. Stability and solubility of these complexes was achieved by using the weakly coordinating anions (WCAs) [Al(OR^F)₄]^? and [F{Al(OR^F)₃}₂]^? {R^F=C(CF₃)₃} and the solvent ortho‐difluorobenzene (o‐DFB). The magnetic properties of Co(bz)₂⁺ were measured and compared in the condensed and gas phases. The weakly bound Co(o‐dfb)₂⁺ salts are of particular interest for the preparation of further Co^I salts, for example, the structurally characterized low‐coordinate 12 valence electron Co(P^tBu₃)₂⁺ and Co(NHC)₂⁺ salts.     

Electrochemical testing of composite electrodes of (La1?x Sr x ) s MnO3 and doped ceria in NO-containing atmosphere

The possibility of using electrochemical cells for removal of NO _x from an exhaust gas with excess O₂ has been examined. (La_1−x Sr _x ) _s MnO₃ (LSM) and ceria doped with Pr or Gd were selected as electrode materials and investigated in three-electrode cells. The electrodes were characterised electrochemically with electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV), and the gas composition monitored while the electrodes were polarised. The electrodes of (La_0.5Sr_0.5)_0.99MnO₃ (LSM50) and Ce_0.8Pr_0.2O_2−δ exhibit higher current densities in 0.1% NO in Ar than in air at 300 to 400 °C during CV. This indicates some apparent selectivity towards NO compared to O₂. The electrodes can remove NO, when polarised to at least −0.6 V vs. Pt/Air at 600 °C, and EIS measurements under polarisation indicate that the kinetics of the electrodes change, when the electrode potential gets below −0.6 V vs. Pt/Air.     

The association between whole body vibration exposure and musculoskeletal disorders in the Swedish work force is confounded by lifting and posture

This was a cross-sectional study based on material representing the Swedish work-force from a survey conducted in 1999, 2001 and 2003 by Statistics Sweden. Exposure to whole body vibration (WBV) was prevalent among agricultural, forestry, fishery workers and among plant and machinery operators based on a sample of 40,000 employed persons. Approximately 70% responders, that are 9798 persons answered both the interview and the questionnaire for the analysis of exposure-response. Exposure to WBV at least half the working time was associated with prevalence ratios above two for musculoskeletal symptoms in the low back, neck, shoulder/arm and hand among workers. When the exposure factors lifting and frequent bending were added to a multivariate analysis, surprisingly the magnitude of association was low between low back symptoms and WBV exposure. Interestingly, the relation between WBV exposure and symptoms in the neck, shoulder/arm and hand had the same or higher magnitude of association even when the possible confounders were in the model. For the neck, low back and shoulder/arm there was a visible increase in prevalence ratio (as high as 5 times) when combined exposures of WBV, lifting, frequent bending, twisted posture and noise were included in the analysis.     

Near-Edge Soft X-ray Absorption Mass Spectrometry of Protonated Melittin

We have investigated the photoionization and photofragmentation yields of gas-phase multiply protonated melittin cations for photon energies at the K-shell absorption edges of carbon, nitrogen, and oxygen. Two similar experimental approaches were employed. In both experiments, mass selected [melittin+qH]^q+ (q=2–4) ions were accumulated in radiofrequency ion traps. The trap content was exposed to intense beams of monochromatic soft X-ray photons from synchrotron beamlines and photoproducts were analyzed by means of time-of-flight mass spectrometry. Mass spectra were recorded for fixed photon energies, and partial ion yield spectra were recorded as a function of photon energy. The combination of mass spectrometry and soft X-ray spectroscopy allows for a direct correlation of protein electronic structure with various photoionization channels. Non-dissociative single and double ionization are used as a reference. The contribution of both channels to various backbone scission channels is quantified and related to activation energies and protonation sites. Soft X-ray absorption mass spectrometry combines fast energy deposition with single and double ionization and could complement established activation techniques.

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A Series of Analogues to the AT2R Prototype Antagonist C38 Allow Fine Tuning of the Previously Reported Antagonist Binding Mode

We here report on our continued studies of ligands binding to the promising drug target angiotensin II type 2 receptor (AT₂R). Two series of compounds were synthesized and investigated. The first series explored the effects of adding small substituents to the phenyl ring of the known selective nonpeptide AT₂R antagonist C38 , generating small but significant shifts in AT₂R affinity. One compound in the first series was equipotent to C38 and showed similar kinetic solubility, and stability in both human and mouse liver microsomes. The second series was comprised of new bicyclic derivatives, amongst which one ligand exhibited a five-fold improved affinity to AT₂R as compared to C38 . The majority of the compounds in the second series, including the most potent ligand, were inferior to C38 with regard to stability in both human and mouse microsomes. In contrast to our previously reported findings, ligands with shorter carbamate alkyl chains only demonstrated slightly improved stability in microsomes. Based on data presented herein, a more adequate, tentative model of the binding modes of ligand analogues to the prototype AT₂R antagonist C38 is proposed, as deduced from docking redefined by molecular dynamic simulations.