Remeasurement at high resolving power in fourier transform ion cyclotron resonance mass spectrometry

The Fourier transform ion cyclotron resonance mass spectrometry remeasurement experiment is demonstrated and evaluated under high resolution conditions. Signal-to-noise enhancement is observed for isotopically resolved bovine insulin peaks at a resolution of ～ 31,000 (full width at half height). The experiment is sensitive to spacecharge effects and resultant changes in scan-to-scan signal-to-noise and resolution. Coulombic repulsion in the ion cloud during the high resolution remeasurement experiment can cause the cyclotron frequency to shift through the duration of the experiment, which results in broadened peak shapes when individual remeasurement spectra are coadded. By either reducing the number of ions in the cell or allowing the ion cloud to diffuse during the lifetime of the experiment, high resolution remeasurement spectra can be coadded without peak broadening or degradation of signal-to-noise ratio.     

Biomimetic synthesis of (±)-aculeatin D

A practical, efficient and diastereoselective synthesis of the cytotoxic and antiprotozoal compound aculeatin D (1) is described, employing a biomimetic oxidative cyclisation cascade reaction to generate the tricyclic system of the natural product. The synthesis proceeds in ten steps from commercially available 1-tetradecanol.     

Quantitative determination of alkylated quaternary amines and their n-hydroxylated metabolites in an enzyme incubation matrix by liquid chromatography electrospray ionization mass spectrometry

A simple, rapid and sensitive reversed-phase liquid chromatography method coupled to electrospray ionization mass spectrometry has been developed for studying the in vitro metabolism of the long-chain quaternary ammonium compounds dodecyltrimethylamine, tetradecyltrimethylamine and hexadecyltrimethylamine. Samples were prepared from the biological matrix by a simple protein precipitation stage. The separation was performed using a BDS Hypersil C8 3 microm particle size (100 x 3 mm i.d.) column with a fast gradient separation (60% B to 100% B) using a mobile phase of 10 mm aqueous ammonium acetate (pH 4.0, with 0.06% triethylamine; (A)-acetonitrile (B) at 0.7 mL min(-1). To minimize contamination of the MS source a switching value was used to divert the solvent front to waste. Decylammonium bromide was used as the internal standard and analytes were identified and quantified by positive ion electrospray selected ion monitoring of their intact molecular cations. The assay had a limit of quantitation of 0.25 microm (6.25 pmol on column) and was linear over the range 0.25--100 microm assay concentration for this series of long-chain quaternary amines. The precision of intra- and inter-day assays was better than 19% and the accuracy was between 93 and 109%. The method was used to assess the in vitro metabolism of the quaternary amines by wild-type cytochrome P450 enzyme CYP 4 A 1 and mutants in an artifical membrane system.     

A reassessment of the transition-metal free suzuki-type coupling methodology

We present here a reassessment of our transition-metal free Suzuki-type coupling protocol. We believe that, although the reaction can be run without the need for addition of a metal catalyst, palladium contaminants down to a level of 50 ppb found in commercially available sodium carbonate are responsible for the generation of the biaryl rather than, as previously suggested, an alternative non-palladium-mediated pathway. We present a revised methodology for Suzuki couplings using ultralow palladium concentrations for use with aryl and vinyl boronic acids and discuss the effects of the purity of the boronic acid on the reaction.     

Interaction of the mu-opioid receptor with GPR177 (Wntless) inhibits Wnt secretion: potential implications for opioid dependence

Background  

Opioid agonist drugs produce analgesia. However, long-term exposure to opioid agonists may lead to opioid dependence. The analgesic and addictive properties of opioid agonist drugs are mediated primarily via the mu-opioid receptor (MOR). Opioid agonists appear to alter neuronal morphology in key brain regions implicated in the development of opioid dependence. However, the precise role of the MOR in the development of these neuronal alterations remains elusive. We hypothesize that identifying and characterizing novel MOR interacting proteins (MORIPs) may help to elucidate the underlying mechanisms involved in the development of opioid dependence.     

Conformational arm-wrestling: battles for stereochemical control in benzamides bearing matched and mismatched chiral 2- and 6-substituents

The orientation of a tertiary amide group adjacent to an aromatic ring may be governed by the stereochemistry of an adjacent chiral substituent. With a chiral substituent in both ortho positions, matched/mismatched pairs of isomers result. Evidence for matched stereochemistry is provided by the clean NMR spectra of single conformers, while mismatching gives poor or unexpected selectivities in the formation of chiral substituents, or mixtures of amide conformers. Attempts to use the match-mismatch effect to select for racemic pairs of enantiomeric substituents, and hence develop a "racemate-sequestering" reagent, are described, along with the use of "matching" to scavenge a single enantiomer of a diamine from material of incomplete enantiomeric purity.     

Aryl trihydroxyborates: easily isolated discrete species convenient for direct application in coupling reactions

A conceptually and practically simple alternative approach to the use of arylboron species as the organometallic component in cross-coupling processes is described whereby trihydroxyborate salts are isolated and directly employed. The protocol derives practical benefit from the ease and convenience of the isolation and subsequent use of the discrete borate salts, eliminates the need for additional base, and aids the use of correct reaction stoichiometry.     

Determination of fluoroquinolones in chicken tissues by LC-coupled electrospray ionisation and atmospheric pressure chemical ionisation

The aim of this work was to develop a method for determining seven quinolones (ciprofloxacin, danofloxacin, enrofloxacin, sarafloxacin, difloxacin, oxolinic acid and flumequine) in chicken muscle by LC coupled to MS. Two ionisation techniques, ESI and atmospheric pressure chemical ionisation (APCI) were compared using standard solutions. LOD and LOQwere determined under the optimised conditions for the two sources. The ESI was found the best for the purpose. The optimised method (LC-ESI-MS) was validated for the simultaneous analysis of the quinolones regulated by European Community in spiked chicken tissues, using norfloxacin as internal standard. Recoveries obtained varied in the range 60-109%. This method was compared with LC-UV method established previously.     

Functional MRI and multivariate autoregressive models

Connectivity refers to the relationships that exist between different regions of the brain. In the context of functional magnetic resonance imaging (fMRI), it implies a quantifiable relationship between hemodynamic signals from different regions. One aspect of this relationship is the existence of small timing differences in the signals in different regions. Delays of 100 ms or less may be measured with fMRI, and these may reflect important aspects of the manner in which brain circuits respond as well as the overall functional organization of the brain. The multivariate autoregressive time series model has features to recommend it for measuring these delays and is straightforward to apply to hemodynamic data. In this review, we describe the current usage of the multivariate autoregressive model for fMRI, discuss the issues that arise when it is applied to hemodynamic time series and consider several extensions. Connectivity measures like Granger causality that are based on the autoregressive model do not always reflect true neuronal connectivity; however, we conclude that careful experimental design could make this methodology quite useful in extending the information obtainable using fMRI.     

New Regioselective Intercalation Reactions

Abstract

The ordered layered double hydroxide, [LiA1₂(OH)₆]CI. 2H₂O exhibits shape-selective ion-exchange intercalation of dicarboxylate anions. Specific isomeric preferences can be controlled by varying the reaction temperatures. The intercalated guests can be quantitatively recovered from the host lattice with concomitant regeneration of the host offering a novel approach in separation science. To illustrate the potential of this new material in separation science, we describe the isolation of pure 1,4-benzenedicarboxylate and 2, 6-naphthalenedicarboxylate from mixtures of their isomers. The neutral organic acids are both monomers in the synthesis of a range of important polyesters.