Water Docking Bias in [4]Helicene

We report on the one‐ and two‐water clusters of [4]helicene, the smallest polycyclic aromatic hydrocarbon with a helical sense, which were captured in the gas phase using high‐resolution rotational spectroscopy. The structures of the complexes are unambiguously revealed using microwave spectra of isotopically enriched species. In the one‐water cluster, the apparent splitting pattern is consistent with a tunneling motion that encompasses an exchange of strongly and weakly bonded water hydrogens. This motion is “locked” in the two‐water cluster. The relevant intermolecular contacts, symmetry, and aromaticity effects are unveiled for the microsolvated chiral topologies. These observations entail the first glance at the structures and internal dynamics of the water binding motifs of a chiral polycyclic aromatic hydrocarbon.     

Strategic analysis of the dairy transportation problem

The dairy transportation problem (DTP) consists of determining the best routes to be performed for collecting milk from farms and delivering it to processing plants. We study the particular case of the province of Quebec, where the Fédération des producteurs de lait du Québec is responsible for negotiating the transportation costs on behalf of producers. Several issues are highlighted in the actual process of designing contracts such as using historical data. We propose an approach based on scenario analysis that consists of revising both the steps and the information used to construct the routes. We develop a generalized tabu search algorithm that integrates the different characteristics of the DTP.     

The impact of blood on liver metabolite profiling – a combined metabolomic and proteomic approach

Metabolomics has entered the well‐established omic sciences as it is an indispensable information resource to achieve a global picture of biological systems. The aim of the present study was to estimate the influence of blood removal from mice liver as part of sample preparation for metabolomic and proteomic studies. For this purpose, perfused mice liver tissue (i.e. with blood removed) and unperfused mice liver tissue (i.e. containing blood) were compared by two‐dimensional gas chromatography time of flight mass spectrometry (GC × GC‐TOFMS) for the metabolomic part, and by liquid chromatography tandem mass spectrometry (LC‐MS/MS) for the proteomic part. Our data showed significant differences between the unperfused and perfused liver tissue samples. Furthermore, we also observed an overlap of blood and tissue metabolite profiles in our data, suggesting that the perfusion of liver tissue prior to analysis is beneficial for an accurate metabolic profile of this organ. Copyright © 2013 John Wiley & Sons, Ltd.     

Localizing Binding Sites on Bioconjugated Hydrogen-Bonded Organic Semiconductors at the Nanoscale

Hydrogen-bonded organic semiconductors are extraordinarily stable organic solids forming stable, large crystallites with the ability to preserve favorable electrical properties upon bioconjugation. Lately, tremendous efforts have been made to use these bioconjugated semiconductors as platforms for stable multifunctional bioelectronics devices, yet the detailed characterization of bio-active binding sites (orientation, density, etc.) at the nanoscale has not been achieved yet. The presented work investigates the bioconjugation of epindolidione and quinacridone, two representative semiconductors, with respect to their exposed amine-functionalities. Relying on the biotin-avidin lock-and-key system and applying the atomic force microscopy (AFM) derivative topography and recognition (TREC) imaging, we used activated biotin to flag crystal-faces with exposed amine functional groups. Contrary to previous studies, biotin bonds were found to be stable towards removal by autolysis. The resolution strength and clear recognition capability makes TREC-AFM a valuable tool in the investigation of bio-conjugated, hydrogen-bonded semiconductors.     

The Development of Stable 3-Nitro-2-pyridinesulfenyl Reagents and Their Application to Peptide Chemistry

Development of 3-Nitro-2-pyridinesulfenyl (Npys) halide reagents and their application to peptide chemistry are discussed     

Knowledge-Based Design of a Biosensor to Quantify Localized ERK Activation in Living Cells

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Detection and identification of the designer benzodiazepine flubromazepam and preliminary data on its metabolism and pharmacokinetics

The appearance of pyrazolam in Internet shops selling ‘research chemicals’ in 2012 marked the beginning of designer benzodiazepines being sold as recreational drugs or ‘self medication’. With recent changes in national narcotics laws in many countries, where two uncontrolled benzodiazepines (phenazepam and etizolam), which were marketed by pharmaceutical companies in some countries, were scheduled, clandestine laboratories seem to turn to poorly characterized research drug candidates as legal substitutes. Following the appearance of pyrazolam, it comes with no surprise that recently, flubromazepam (7‐bromo‐5‐(2‐fluorophenyl)‐1,3‐dihydro‐2H‐1,4‐benzodiazepin‐2‐one), a second designer benzodiazepine, was offered on the market. In this article, this new compound was characterized using nuclear magnetic resonance, gas chromatography‐mass spectrometry (GC–MS), liquid chromatography–mass spectrometry (LC–MS/MS) and liquid chromatography quadrupole time‐of‐flight MS (LC–Q–ToF–MS). Additionally, a study was carried out, in which one of the authors consumed 4 mg of flubromazepam to gain preliminary data on the pharmacokinetic properties and the metabolism of this compound. For this purpose, serum as well as urine samples were collected for up to 31 days post‐ingestion and analyzed applying LC–MS/MS and LC–Q‐ToF‐MS techniques. On the basis of this study, flubromazepam appears to have an extremely long elimination half‐life of more than 100 h. One monohydroxylated compound and the debrominated compound could be identified as the predominant metabolites, the first allowing a detection of a consumption for up to 28 days post‐ingestion when analyzing urine samples in our case. Additionally, various immunochemical assays were evaluated, showing that the cross‐reactivity of the used assay seems not to be sufficient for safe detection of the applied dose in urine samples, bearing the risk that it could be misused in drug‐withdrawal settings or in other circumstances requiring regular drug testing. Furthermore, it may be used in drug‐facilitated crimes without being detected. Copyright © 2013 John Wiley & Sons, Ltd.     

Hyrtimomines,indole alkaloids from Okinawan marine sponges Hyrtios spp.

Six new indole alkaloids, hyrtimomines F–K (1–6), were isolated from Okinawan marine sponges Hyrtios spp. The structures of 1–6 were elucidated on the basis of spectroscopic analysis. Hyrtimomine F (1) is a structurally unique bisindole alkaloid possessing an α-keto-?-caprolactam ring, while hyrtimomine G (2) is a symmetrical bisindole alkaloid. Hyrtimomines H–K (3–6) are indole alkaloids possessing β-carboline skeleton with an imidazolium unit. Antimicrobial activities of hyrtimomines F–K (1–6) were evaluated.