Identification and profiling of targeted oxidized linoleic acid metabolites in rat plasma by quadrupole time‐of‐flight mass spectrometry

Linoleic acid (LA) and LA‐esters are the precursors of LA hydroperoxides, which are readily converted to 9‐ and 13‐hydroxy‐?octadecadienoic acid (HODE) and 9‐ and 13‐oxo‐?octadecadienoic acid (oxo ODE) metabolites in vivo. These four oxidized LA metabolites (OXLAMs) have been implicated in a variety of pathological conditions. Therefore, their accurate measurement may provide mechanistic insights into disease pathogenesis. Here we present a novel quadrupole time‐of‐flight mass spectrometry (Q‐TOFMS) method for quantitation and identification of target OXLAMs in rat plasma. In this method, the esterified OXLAMs were base‐hydrolyzed and followed by liquid–liquid extraction. Quantitative analyses were based on one‐point standard addition with isotope dilution. The Q‐TOFMS data of target metabolites were acquired and multiple reaction monitoring extracted‐ion chromatograms were generated post‐acquisition with a 10 ppm extraction window. The limit of quantitation was 9.7–35.9 nmol/L depending on the metabolite. The method was reproducible with a coefficient of variation of <18.5%. Mean concentrations of target metabolites in rat plasma were 57.8, 123.2, 218.1 and 57.8 nmol/L for 9‐HODE, 13‐HODE, 9‐oxoODE and 13‐oxoODE, respectively. Plasma levels of total OXLAMs were 456.9 nmol/L, which correlated well with published concentrations obtained by gas chromatography/mass spectrometry (GC/MS). The concentrations were also obtained utilizing a standard addition curve approach. The calibration curves were linear with correlation coefficients of >0.991. Concentrations of 9‐HODE, 13‐HODE, 9‐oxoODE and 13‐oxoODE were 84.0, 138.6, 263.0 and 69.5 nmol/L, respectively, which were consistent with the results obtained from one‐point standard addition. Target metabolites were simultaneously characterized based on the accurate Q‐TOFMS data. This is the first study of secondary LA metabolites using Q‐TOFMS. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.     

Metal Organic Precursors for Yttria

Abstract

Several carboxylic acid derivatives of yttrium that have potential as metal organic deposition (MOD) precursors for yttria were prepared and characterized. These included a traditional MOD precursor bearing 2-ethylhexanoate ligands and a new class of precursors bearing poly-ether carboxylic acid ligands. Notably, the latter complexes are viscous liquids.     

An Efficient Method for the In Vitro Production of Azol(in)e‐Based Cyclic Peptides

Heterocycle‐containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine‐derived enzymes and substrates obtained from a family of ribosomally produced and post‐translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non‐native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6–9 residues representing 11 out of the 20 canonical amino acids.     

Preparation and stereochemistry of methyl 3-(and 4)-p-chlorothiophenoxy-1-methylpiperidine-4-(and 3)-carboxylates,and cyclization to benzothiopyranopyridinones

The title piperidines were prepared by (a) methanolysis of the corresponding nitriles and (b) addition of p-chlorothiophenol to the appropriate tetrahydropyridines. Three esters were obtained with stereochemistry assigned by nmr analysis: 2 [3(a) SAr, 4(e) CO₂Me], 5 [4(e) SAr, 3(e) CO₂Me], 6 [4(a) SAr, 3(e) CO₂Me]. Compounds 2 and 6 cyclized in 70% sulfuric acid. The product structures were established by X-ray crystallography and, surprisingly, both had trans-fused rings. Compound 5 , however, did not cyclize but gave 4-(methylthio)chlorobenzene as the sole isolated product.     

Transient excited-state absorption of the liquid crystal CB15 [4-(2-methylbutyl)-4-cyanobiphenyl] in its isotropic phase

Liquid crystals are known to possess large electronic optical non-linearities. Transient photoinduced absorption is not commonly applied to liquid crystals, but it is a powerful technique by which to examine the excited-state absorption (ESA) and hence the non-linear absorption of molecular systems. We show that measurements of this kind can give an insight into the dominant mechanisms of picosecond non-linear optical response in liquid crystals, and together with semi-empirical quantum chemical calculations appropriate assignments of the absorptions can be made. In particular, we report measurements of the transient ESA of the liquid crystal CB15 [4-(2-methylbutyl)-4-cyanobiphenyl] in its isotropic phase using femtosecond pump-probe spectroscopy in the wavelength range from 400 to 1000 nm. By pumping directly into the first excited state (S₁) we identify at least four transient ESAs which contribute to the non-linear response up to a time of 1 ns after excitation. These features show a linear dependence with pump intensity. There also exists weak two-photon absorption (TPA) into S₁ at 650 nm, giving a similar ESA. Furthermore, we show that a semi-empirical quantum-chemical treatment of a single molecular unit of CB15 using the AMI Hamiltonian gives good agreement with the observed spectra, and implies that the dominant ESA in the picosecond regime can be attributed principally to singlet-singlet transitions from monomer units; but there is also a possible contribution to the ESAs by excimer absorption. On the time scale of our experiment we see no evidence of triplet-triplet absorptions, and we have also measured a fluorescence quantum yield of 20%.     

The peeling of a flexible strip attached by a cavitating viscous adhesive

Summary A theory is presented for the peeling of a completely flexible strip from a plane rigid surface to which it had been attached by a thin layer of adhesive. The adhesive is taken to be a purely viscousNewtonian liquid, and is assumed to fail by cavitation or the dilation of bubbles of trapped gas. By such a model a relation between peeling rate and peeling force (which in the absence of any reduction in pressure within the cavities would be linear) may be found.The significance of surface tension in defining boundary conditions in dividing liquid layers, is discussed, and the implication of a vanishing significance of surface tension on the limiting form of these conditions, provides a basis for the analysis.The absence of relevant experimental data precludes direct comparison, but the physical appearance of real adhesives in peeling is seen to be not inconsistent with the model proposed.This work was performed at the Cavendish Laboratory, University of Cambridge. The assistance of an Australian Commonwealth Public Service Board Scholarship, and the computing facilities at the Mathematical Laboratory, University of Cambridge, England, is gratefully acknowledged.     

Settlement of Ulva zoospores on patterned fluorinated and PEGylated monolayer surfaces

Various designs for coatings that resist the attachment of marine organisms are based on the concept of "ambiguous" surfaces that present both hydrophobic and hydrophilic functionalities as surface domains. In order to facilitate the optimal design of such surfaces, information is needed on the scale of the domains that the settling stages of marine organisms are able to distinguish. Previous experiments showed that Ulva zoospores settle (attach) in high numbers onto fluorinated monolayers compared to PEGylated monolayers. The main aim of the present study was to determine, when zoospores of the green alga Ulva are presented with a choice of fluorinated or PEGylated surfaces, what the minimum dimensions of the two types of surface are that zoospores can detect and consequently settle on. Silicon wafers were chemically modified to produce a pattern of squares containing alternating fluorinated and PEGylated stripes of different widths on either a uniform fluorinated or PEGylated background. Each 1 cm x 1 cm square contained stripes with widths of 500, 200, 100, 50, 20, 5, or 2 microm as well as an unpatterned square with a chemistry opposite that of the background. Spores were selective in choosing where to settle, settling at higher densities on fluorinated stripes compared to PEGylated stripes. However, the magnitude of response, and the consequences for settlement on patterned areas overall, was dependent on both the width of the stripes and the chemistry of the background. The data are discussed in relation to the ability of spores to "choose" favorable sites for settlement and the implications for the development of novel antifouling coatings.     

Extensions of operator algebras I

We transcribe a portion of the theory of extensions of C^∗-algebras to general operator algebras. We also include several new general facts about approximately unital ideals in operator algebras and the C^∗-algebras which they generate.     

Watching electrons move in real time: ultrafast infrared spectroscopy of a polymer blend photovoltaic material

The dynamics of photoinduced charge separation and the motion of the resulting electrons are examined in an organic photovoltaic material with a combination of ultrafast two-dimensional infrared (2D IR) and visible pump-infrared probe (Vis-IR) spectroscopy. The carbonyl (C=O) stretch of the butyric acid methyl ester group of a functionalized fullerene, PCBM, is probed as a local vibrational reporter of the dynamics in a blend of the fullerene with a conjugated polymer, CN-MEH-PPV. Charge transfer occurs preferentially at the interfaces between the roughly spherical domains of fullerene molecules and the polymer. Comparison of the Vis-IR and 2D IR spectra reveals that the fullerene molecules at the interfaces of the domains possess higher frequency carbonyl vibrational modes, while molecules in the centers of the domains have lower frequency modes relative to the center of the transition. The correlation between the frequency of a carbonyl mode and the spatial position of its host fullerene molecule provides a means to observe the motion of electrons within individual domains through the spectral evolution of the carbonyl bleach. From the spectral evolution, we find that the average radial velocity of electrons is 1-2 m/s, which suggests an intrinsic mobility that is at least one order of magnitude greater than the mobility in the polymer blend. The results indicate that organic solar cells with higher mobility and thus efficiency may be realized by controlling the morphology of the polymer and fullerene materials.