Binding Mode and Structure–Activity Relationships around Direct Inhibitors of the Nrf2–Keap1 Complex

An X‐ray crystal structure of Kelch‐like ECH‐associated protein (Keap1) co‐crystallised with (1S,2R)‐2‐[(1S)‐1‐[(1,3‐dioxo‐2,3‐dihydro‐1H‐isoindol‐2‐yl)methyl]‐1,2,3,4‐tetrahydroisoquinolin‐2‐carbonyl]cyclohexane‐1‐carboxylic acid (compound (S,R,S)‐ 1 a ) was obtained. This X‐ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)‐ 1 a , as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently.     

Separation of Enantiomeric Triacylglycerols by Chiral‐Phase HPLC

Liquid chromatography–atmospheric pressure chemical ionization mass spectrometry (LC–MS/APCI) with a chiral phase was used for separation of triacylglycerols (TAG) obtained either by organic synthesis or isolated from different algal species. We present chromatographic characteristics and tandem mass spectra of enantiomers and positional isomers (regioisomers) of C16, C18 and C20 polyunsaturated fatty acids. The retention time was found to depend on the structure of the given TAG, increasing with increasing number of double bonds and decreasing with increasing number of the carbons in TAG, with the exception of dieicosapentaenoyl‐palmitoyl‐glycerols.     

Effect of Storage Conditions and Antioxidants on the Oxidative Stability of Sunflower–Chia Oil Blends

The mixture of different proportions of sunflower with chia oil provides a simple method to prepare edible oils with a wide range of desired fatty acid compositions. Sunflower–chia (90:10 and 80:20 wt/wt) oil blends with the addition of rosemary (ROS), ascorbyl palmitate (AP) and their blends (AP:ROS) were formulated to evaluate the oxidative stability during storage at two temperature levels normally used, cool (4 ± 1 °C) and room temperature (20 ± 2 °C) for a period of 360 days. Peroxide values (PV) of the oil blends with antioxidants stored at 4 ± 1 °C showed levels ≤10.0 mequiv O₂/kg oil; the lowest levels of PV were found for blends with AP:ROS. Values higher than 10.0 mequiv O₂/kg were observed between 120–240 days for oil blends stored at 20 ± 2 °C. Similar trends were observed with p-anisidine and Totox values. The oxidative stability determined by the Rancimat method and differential scanning calorimetry showed a greater susceptibility of the oils to oxidative deterioration with increasing unsaturated fatty acids content. The addition of antioxidants increased the induction time and decreased the Arrhenius rate constant, indicating an improvement in the oxidative stability for all the oil blends. Temperature had a strong influence on the stability of these blends during storage.     

Coulomb interactions in Ga LMIS

For low emission currents from around 1 microA Ga liquid-metal ion sources (LMIS) produce fine optically bright ion beams that are strongly limited by the Coulomb particle-particle interactions. We present computations of the energy spread, the beam virtual crossover size, and beam brightness based on direct numerical integration of the equation of motion in a numerically calculated field for a number of dimensions of the emission tip. The Coulomb particle-particle interactions are included into the calculation of ion beam evolution. A comparison with experimental data allows to estimate the tip size.     

The hydrocarbon fraction of virgin olive oil and changes resulting from refining

In numerous Spanish virgin olive oils, 6,10-dimethyl-1-undecene, various sesquiterpenes, the series ofn-alkanes from C14 to C35, n-8-heptadecene and squalene are the only less volatile components detected by gas chromatography in the hydrocarbon fraction. In oils from olives of the Arbequine variety, a series ofn-9-alkenes has also been found. In refined oils, notable features are the absence of the most volatile compounds and the appearance of other hydrocarbons produced during the refining process. Among these,n-alkanes, alkadienes (mainlyn-hexacosadiene), stigmasta-3,5-diene, isomerization products of squalene, isoprenoidal polyolefins coming from hydroxy derivatives of squalene and steroidal hydrocarbons derived from 24-methylene cycloartanol were identified. Physical refining produces larger amounts of degradation products and greater losses ofn-alkanes than chemical processing. Squalene is the major hydrocarbon component in all oils, both virgin and refined. The ranges of concentration for the different hydrocarbons found in Spanish virgin olive oils are presented.     

Design and performance of a combined secondary ion mass spectrometry-scanning probe microscopy instrument for high sensitivity and high-resolution elemental three-dimensional analysis

State-of-the-art secondary ion mass spectrometry (SIMS) instruments allow producing 3D chemical mappings with excellent sensitivity and spatial resolution. Several important artifacts however arise from the fact that SIMS 3D mapping does not take into account the surface topography of the sample. In order to correct these artifacts, we have integrated a specially developed scanning probe microscopy (SPM) system into a commercial Cameca NanoSIMS 50 instrument. This new SPM module, which was designed as a DN200CF flange-mounted bolt-on accessory, includes a new high-precision sample stage, a scanner with a range of 100 μm in x and y direction, and a dedicated SPM head which can be operated in the atomic force microscopy (AFM) and Kelvin probe force microscopy modes. Topographical information gained from AFM measurements taken before, during, and after SIMS analysis as well as the SIMS data are automatically compiled into an accurate 3D reconstruction using the software program "SARINA," which was developed for this first combined SIMS-SPM instrument. The achievable lateral resolutions are 6 nm in the SPM mode and 45 nm in the SIMS mode. Elemental 3D images obtained with our integrated SIMS-SPM instrument on Al/Cu and polystyrene/poly(methyl methacrylate) samples demonstrate the advantages of the combined SIMS-SPM approach.     

Insights into the chemical behavior of zinc dialkyldithiophosphate anti-wear additives in their isomeric and decomposed forms through molecular simulation

Ab initio molecular dynamics simulations and static quantum chemical calculations at the density functional level of theory have been applied to study zinc dialkyldithiophosphate (ZDDP) engine oil anti-wear additives in their parent, isomeric and decomposed forms to identify differences in the basic finite temperature chemical behavior of these species that may be related to the formation of ZDDP anti-wear films. It was found that the isomers, which contain Zn–O bonds, exhibited finite temperature behavior leading to the dissociation of these bonds, while the parent ZDDP molecule, which contains only Zn–S bonds, did not. The dissociation of the Zn–O bonds improves the abilities of these molecules to participate in film formation reactions as electron donors and hence the transformation of the ZDDP molecule into species with Zn–O bonds, such as the isomers and decomposed species, may aid in anti-wear film formation. It was observed that the dissociation of the Zn–O bonds allowed the molecules to attain rearranged structures where the coordination at the zinc atom had significantly changed and it was found that these rearranged structures could decompose through the elimination of metathiophosphates (MTPs). The results of static density functional theory calculations on all species indicated that the elimination of MTPs was energetically favorable at high temperatures, however, the ability of the parent molecule to participate in rearrangement determines whether decomposition will occur. The fact that these species readily participate in reactions that lead to MTP formation is relevant within the context of ZDDP anti-wear film formation since the MTP molecules possess properties that make them ideal precursors to the thiophosphate networks that are thought to comprise these films. Overall, the results of this study indicate that differences between the ZDDP molecule, its isomers and decomposition products exist that may affect the abilities of these species to participate in the formation of anti-wear films. This information will be useful within the development of an overall mechanism for the formation of ZDDP anti-wear films.     

Morphological investigation of ternary and semicrystalline organic–inorganic hybrid nanocomposite

Journal of Materials Science - Organic–inorganic (O–I) hybrid nanocomposites have already been widely investigated in the optoelectronic industry and are emerging in the biomedical...     

Anisotropic transport properties of graphene-based conductor materials

Journal of Materials Science - We analyzed nanographite-based materials in a combined study including experimental analysis via 4-point probe STM and simulation to provide a complete picture of...     

The impact of alum discharges on a natural tropical wetland in Uganda

Alum sludge discharge effects on a natural wetland on the shores of Lake Victoria at Gaba in Uganda has been investigated. The water quality in the swamp, the sediment chemistry and plant growth and productivity were monitored. The subsequent application of alum sludge discharges shows no immediate, noticeable, adverse overall effects on the water quality and sediment chemistry. A distinct effect on plant productivity was noted in Cyperus papyrus L. the dominant macrophyte in the Gaba swamp resulting in a low productivity rate of 5.1 g/m2 d and the apparent phasing out of this macrophyte in the swamp. Phragmites mauritianus (Kunth) exhibited better tolerance to alum sludge. Clear indications are cited of the ecosystem degrading and cumulative effects being marked over a longer time frame.