Microphysiometric Measurement of PAF Receptor Responses to Ginkgolides

Microphysiometry was used to evaluate the effects of terpene trilactone and flavonoid constituents of Ginkgo biloba on human platelet‐activating‐factor receptor (PAFR). Inhibition of the platelet‐activating factor response by terpene trilactones was confirmed using this functional assay. Ginkgolide B (GB) and 10‐O‐benzyl‐GB showed the strongest inhibition (81 and 93%, resp.) of the PAFR response, while the flavonoids rutin, quercetin, and kaempferol showed negligible response inhibition. G. biloba extract mixtures were also tested, and results indicate possible synergistic effects among various components.     

Design,Synthesis, and Phenotypic Profiling of Pyrano‐Furo‐Pyridone Pseudo Natural Products

Natural products (NPs) inspire the design and synthesis of novel biologically relevant chemical matter, for instance through biology‐oriented synthesis (BIOS). However, BIOS is limited by the partial coverage of NP‐like chemical space by the guiding NPs. The design and synthesis of “pseudo NPs” overcomes these limitations by combining NP‐inspired strategies with fragment‐based compound design through de novo combination of NP‐derived fragments to unprecedented compound classes not accessible through biosynthesis. We describe the development and biological evaluation of pyrano‐furo‐pyridone (PFP) pseudo NPs, which combine pyridone‐ and dihydropyran NP fragments in three isomeric arrangements. Cheminformatic analysis indicates that the PFPs reside in an area of NP‐like chemical space not covered by existing NPs but rather by drugs and related compounds. Phenotypic profiling in a target‐agnostic “cell painting” assay revealed that PFPs induce formation of reactive oxygen species and are structurally novel inhibitors of mitochondrial complex I.     

Determination of chlormequat and mepiquat in pear,tomato, and wheat flour using on-line solid-phase extraction (Prospekt) coupled with liquid chromatography-electrospray ionization tandem mass spectrometry

A new methodology based on pressurized liquid extraction (PLE) followed by LC-MS is presented for the simultaneous and unequivocal determination of alkylphenol ethoxylates (APEOs) and their degradation products, alkylphenols (APs) and alkylphenoxy carboxylates (APECs), in sediment samples. The protocol, applicable to a full range of APEO oligomers and degradation products, permits the sensitive and selective determination of APEOs (nEO = 1-15), APECs (nEO = 0-1) and APs at low ppb levels (LODs = 1-5 microg/kg) in sediment samples. Optimization of the operational parameters of PLE clearly demonstrates that significant thermal losses of APs occur during extraction at elevated temperatures. The loss of octylphenol (OP) at 100 degrees C was 61.2% and of nonylphenol (NP) 40.0%, whereas other compounds were completely recovered. Thus, to avoid losses due to the volatility of alkylphenols, a low extraction temperature should be applied. The conditions that gave the best results for all target compounds were as follows: extraction solvent mixture, methanol-acetone (1:1, v/v); temperature, 50 degrees C; pressure, 1500 p.s.i.; two static cycles. Using PLE and a subsequent clean-up with solid-phase extraction (SPE), the simultaneous extraction of APEOs, APs and APECs from sediment samples was achieved yielding recoveries >70% and producing low MS background noise. The developed methodology was applied on a routine basis to the analysis of alkylphenolic compounds in sediment samples. APEOs and their persistent degradation products were detected in significant concentrations in sediments from Portuguese rivers, especially at sites situated in the proximity of industrial plants (mainly the textile industry). The total concentration of alkylphenolic compounds (APEOs+APs+APECs) ranged from 155 to 2400 microg/kg. Of all the alkylphenolic compounds, NP comprised 40 to 50% with concentrations up to 1172 microg/kg.     

The first di‐μ‐hydro­xo‐bridged binuclear copper complex containing a bis‐guanidine ligand

The present structure determination of di‐μ‐hydroxo‐bis{[N,N′‐bis­(dipiperidino­methyl­ene)­propane‐1,3‐di­amine‐κ²N,N′]copper(II)} bis­(hexa­fluoro­phosphate), [Cu₂(OH)₂(C₂₅H₄₆N₆)₂](PF₆)₂, is the first to crystallographically characterize a Cu₂(μ‐OH)₂ complex with a bidentate guanidine ligand. The cation lies on a crystallographic inversion centre and shows planar fourfold coordination of the copper centres. The Cu₂(μ‐OH)₂ species can be distinguished from Cu₂(μ‐O)₂ by the Cu—O bond lengths. The packing is determined by strong intermolecular anion–cation hydrogen bonds.     

1H and 13C NMR signal assignment of cucurbitacin derivatives from Citrullus colocynthis (L.) Schrader and Ecballium elaterium L. (Cucurbitaceae)

2D NMR-derived 1H and 13C NMR signal assignments of six structurally closely related cucurbitacin derivatives are presented. The investigated 2-O-beta-D-glucopyranosylcucurbitacins I, J, K, and L were obtained from Citrullus colocynthis (L.) Schrader whereas the aglyca cucurbitacin E and I were isolated from Ecballium elaterium L.     

Manipulation of microalgal lipid production using genetic engineering

Applied Biochemistry and Biotechnology - Genetic transformation of two species of diatoms has been accomplished by introducing chimeric plasmid vectors containing a bacterial antibiotic resistance...     

Simulation of 59Co NMR chemical shifts in aqueous solution

59Co chemical shifts were computed at the GIAO-B3LYP level for [Co(CN)6]3-, [Co(H2O)6]3+, [Co(NH3)6]3+, and [Co(CO)4]- in water. The aqueous solutions were modeled by Car-Parrinello molecular dynamics (CPMD) simulations, or by propagation on a hybrid quantum-mechanical/molecular-mechanical Born-Oppenheimer surface (QM/MM-BOMD). Mean absolute deviations from experiment obtained with these methods are on the order of 400 and 600 ppm, respectively, over a total delta(59Co) range of about 18,000 ppm. The effect of the solvent on delta(59Co) is mostly indirect, resulting primarily from substantial metal-ligand bond contractions on going from the gas phase to the bulk. The simulated solvent effects on geometries and delta(59Co) values are well reproduced by using a polarizable continuum model (PCM), based on optimization and perturbational evaluation of quantum-mechanical zero-point corrections.