First interlaboratory exercise on non-steroidal anti-inflammatory drugs analysis in environmental samples

Comparability of monitoring data are essential for any meaningful assessment and for the management of environmental risks of emerging pollutants. The reliability and comparability of data at European level is often limited, because analytical methods for emerging pollutants are often not fully validated, not harmonized or not suitable for all relevant matrices. This paper describes a collaborative interlaboratory exercise for the analysis of non-steroidal anti-inflammatory drugs (NSAIDs) residues in freshwater and wastewater, held in the framework of the EU project "Network of reference laboratories for monitoring of emerging environmental pollutants" (NORMAN). The NSAID compounds selected in this study were ketoprofen, naproxen, ibuprofen and diclofenac. Thirteen laboratories distributed along nine European Countries (Austria, France, Germany, Greece, Italy, Slovak Republic, Slovenia, Spain, and Switzerland) took part in this exercise, 126 samples were analyzed and a total number of 473 values in duplicate were collected. Samples selected in this study include environmental water (river water and waste water) and artificial water (fortified environmental and distilled water) with different ranges of complexity. Two analytical methods were proposed by the organiser; one is based on the use of solid phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the second one is based on SPE followed by gas-chromatography-mass spectrometry (GC-MS), however, in the first round some different approaches were also admitted. The main goals of this interlaboratory comparison were to evaluate the available analytical schemes for NSAID analysis in natural waters, to evaluate the repeatability (r) and reproducibility (R) between participating laboratories, and to evaluate the influence of the analytical method and sample matrices on the results.     

Trace level determination of beta-blockers in waste waters by highly selective molecularly imprinted polymers extraction followed by liquid chromatography-quadrupole-linear ion trap mass spectrometry

This paper describes the development of an analytical methodology to determine eight beta-blockers in waste waters using molecularly imprinted polymers (MIPs) as extraction and pre-concentration material, followed by liquid chromatography-quadrupole-linear ion trap mass spectrometry (LC-QqLIT MS). The advantages offered by MIPs, in terms of selectivity and specificity, were compared with the most commonly polymeric materials used (the lipophilic-hydrophilic balanced Oasis HLB cartridges). Even though recoveries achieved with both sorbents were similar, ranging from 50 to 110% for sewage treatment plant (STP) effluent and 40-110 for STP influent, respectively, MIPs provided lower method detection limits than Oasis HLB, due to their specificity for target analytes and closely related analogues. Method detection limits (MDL) achieved using MIPs ranged from 0.2 to 6.4 ng/L for STP effluent and from 0.4 to 6.5 ng/L for STP influent. To highlight the advantages of MIPs against conventional polymeric cartridges, a detailed matrix effects study as well as cross reactivity tests were performed. For the latter purpose, the extraction efficiency of some pharmaceuticals and pesticides belonging to different therapeutic classes was assessed. LC-QqLIT MS, used for quantification and confirmation, proved to be a powerful analytical tool, as instrumental detection limits (IDL) achieved ranged from 0.2 to 2.7 pg injected (in multiple reaction monitoring mode (MRM)). In addition the inclusion of high sensitive MS/MS scans for each compound when working in Information Dependent Acquisition mode (IDA) provided extra confirmation for unequivocal identification of target compounds in complex environmental matrices.     

MiniAp‐4: A Venom‐Inspired Peptidomimetic for Brain Delivery

Drug delivery across the blood–brain barrier (BBB) is a formidable challenge for therapies targeting the central nervous system. Although BBB shuttle peptides enhance transport into the brain non‐invasively, their application is partly limited by lability to proteases. The present study proposes the use of cyclic peptides derived from venoms as an affordable way to circumvent this drawback. Apamin, a neurotoxin from bee venom, was minimized by reducing its complexity, toxicity, and immunogenicity, while preserving brain targeting, active transport, and protease resistance. Among the analogues designed, the monocyclic lactam‐bridged peptidomimetic MiniAp‐4 was the most permeable. This molecule is capable of translocating proteins and nanoparticles in a human‐cell‐based BBB model. Furthermore, MiniAp‐4 can efficiently deliver a cargo across the BBB into the brain parenchyma of mice.     

Tuning of ruthenium complex properties using pyrrole- and pyrrolidine-containing polypyridine ligands

The effect of pyrrole- and pyrrolidine-containing ligands (L) on the properties of heteroleptic [RuL2dcbpy]2+ complexes has been investigated. TiO2 electrodes modified with the new complexes exhibited extended absorption domains and high absorbances. Providing that a cobalt-based mediator was used for regeneration of the RuII state, good incident photon-to-current efficiency (near 80%) values were obtained in the pyrrole series.     

A concise asymmetric synthesis of torcetrapib

Optically active torcetrapib was synthesized in seven steps from achiral precursors without the need for protecting groups, utilizing an enantioselective aza-Michael reaction to achieve asymmetry.     

Lifted collocation integrators for direct optimal control in ACADO toolkit

This paper presents a class of efficient Newton-type algorithms for solving the nonlinear programs (NLPs) arising from applying a direct collocation approach to continuous time optimal control. The idea is based on an implicit lifting technique including a condensing and expansion step, such that the structure of each subproblem corresponds to that of the multiple shooting method for direct optimal control. We establish the mathematical equivalence between the Newton iteration based on direct collocation and the proposed approach, and we discuss the computational advantages of a lifted collocation integrator. In addition, we investigate different inexact versions of the proposed scheme and study their convergence and computational properties. The presented algorithms are implemented as part of the open-source ACADO code generation software for embedded optimization. Their performance is illustrated on a benchmark case study of the optimal control for a chain of masses. Based on these results, the use of lifted collocation within direct multiple shooting allows for a computational speedup factor of about 10 compared to a standard collocation integrator and a factor in the range of 10–50 compared to direct collocation using a general-purpose sparse NLP solver.     

From chiral vibration to static chirality in (135)Nd

Electromagnetic transition probabilities have been measured for the intraband and interband transitions in the two sequences in the nucleus (135)Nd that were previously identified as a composite chiral pair of rotational bands. The chiral character of the bands is affirmed and it is shown that their behavior is associated with a transition from a vibrational into a static chiral regime.     

A Direct Fluorescent Activity Assay for Glycosyltransferases Enables Convenient High-Throughput Screening: Application to O-GlcNAc Transferase

Glycosyltransferases carry out important cellular functions in species ranging from bacteria to humans. Despite their essential roles in biology, simple and robust activity assays that can be easily applied to high-throughput screening for inhibitors of these enzymes have been challenging to develop. Herein, we report a bead-based strategy to measure the group-transfer activity of glycosyltransferases sensitively using simple fluorescence measurements, without the need for coupled enzymes or secondary reactions. We validate the performance and accuracy of the assay using O-GlcNAc transferase (OGT) as a model system through detailed Michaelis–Menten kinetic analysis of various substrates and inhibitors. Optimization of this assay and application to high-throughput screening enabled screening for inhibitors of OGT, leading to a novel inhibitory scaffold. We believe this assay will prove valuable not only for the study of OGT, but also more widely as a general approach for the screening of glycosyltransferases and other group-transfer enzymes.     

Biomimetic oxygen reduction by cofacial porphyrins at a liquid-liquid interface

Oxygen reduction catalyzed by cofacial metalloporphyrins at the 1,2-dichlorobenzene-water interface was studied with two lipophilic electron donors of similar driving force, 1,1'-dimethylferrocene (DMFc) and tetrathiafulvalene (TTF). The reaction produces mainly water and some hydrogen peroxide, but the mediator has a significant effect on the selectivity, as DMFc and the porphyrins themselves catalyze the decomposition and the further reduction of hydrogen peroxide. Density functional theory calculations indicate that the biscobaltporphyrin, 4,5-bis[5-(2,8,13,17-tetraethyl-3,7,12,18-tetramethylporphyrinyl)]-9,9-dimethylxanthene, Co(2)(DPX), actually catalyzes oxygen reduction to hydrogen peroxide when oxygen is bound on the "exo" side ("dock-on") of the catalyst, while four-electron reduction takes place with oxygen bound on the "endo" side ("dock-in") of the molecule. These results can be explained by a "dock-on/dock-in" mechanism. The next step for improving bioinspired oxygen reduction catalysts would be blocking the "dock-on" path to achieve selective four-electron reduction of molecular oxygen.