Improvement of derivatized amino acid detection sensitivity in micellar electrokinetic capillary chromatography by means of acid-induced pH-mediated stacking technique

Derivatization is a frequently used sample preparation procedure applicable to the enhancement of analyte detection sensitivity. Amino acids mostly require derivatization prior to electrophoretic or chromatographic analysis, especially if spectrophotometric detection is used. This study presents an on-line preconcentration technique for derivatized amino acids. The sensitivity of the method was improved by the utilization of the proposed acid-induced pH-mediated stacking mechanism. The method is demonstrated by preconcentration of amino acids labeled with 2,4-dinitrofluorobenzene. Use of optimized conditions for a large sample volume injection (40 s, 13.8 kPa) followed by electrokinetic injection of 0.1 M HCl (20 s, 10 kV) gave a 20- to 30-fold enhancement of sensitivity. The significance of the sweeping mechanism and pseudo-isotachophoresis for the on-line sample focusing and the influence of parameters on the preconcentration process were discussed. The applicability of the elaborated method was demonstrated using human urine samples.     

LC-MS/MS determination of potential endocrine disruptors of cortico signalling in rivers and wastewaters

A targeted analytical method was established to determine a large number of chemicals known to interfere with the gluco- and mineralocorticoid signalling pathway. The analytes comprise 30 glucocorticoids and 9 mineralocorticoids. Ten out of these corticosteroids were primary metabolites. Additionally, 14 nonsteroids were included. These analytes represent a broader range of possible adverse modes of action than previously reported. For the simultaneous determination of these structurally diverse compounds, a single-step multimode solid-phase extraction and pre-concentration was applied. Extracts were separated by a short linear HPLC gradient (20 min) on a core shell RP column (2.7 μm particle size) and compounds identified and quantified by LC-MS/MS. The method provided excellent retention time reproducibility and detection limits in the low nanograms per litre range. Untreated hospital wastewater, wastewater treatment plant influent, treated effluent and river waters were analysed to demonstrate the applicability of the method. The results show that not all compounds were sufficiently eliminated by the wastewater treatment, resulting in the presence of several steroids (～20 ng/L) and nonsteroids in the final effluent, some of them at high concentrations up to 200 ng/L. Most of the detected mono-hydroxylated steroidal transformation products were found at significantly higher concentrations than their parent compounds. We therefore recommend to include these potentially bioactive metabolites in environmental toxicity assessment.     

Development of a broad spectrum method for measuring flame retardants - Overcoming the challenges of non-invasive human biomonitoring studies

Flame retardants (FRs), such as polybrominated diphenyl ethers (PBDEs) and phosphate flame retardants (PFRs), are a diverse group of compounds that are used to improve fire safety in many consumer products, such as furniture, textiles, electronics, etc. As these compounds are potentially harmful for human health, there is a need to better understand human exposure. Exposure to environmental contaminants can be monitored by the measurement of external sources of exposures and also by the determination of contaminant levels in human samples. For ethical and practical reasons, noninvasive matrices, such as hair, are preferred but, unfortunately, not widely used due to methodological limitations. A major challenge is sample availability: only small amounts can be sampled per individual. Multi-residue methods are therefore essential in order to determine multiple compounds in low sample amounts. In the framework of the FP7 project (INFLAME), an analytical method for the simultaneous determination of PBDEs and PFRs in human hair has been optimized and validated. Before extraction, hair samples (200 mg) were denaturated in nitric acid (HNO₃) for 25 min at 25 °C. Consecutively, the samples were extracted using a mixture of hexane:dichloromethane, and extracts were further fractionated on Florisil. Fraction A which contained PBDEs was additionally cleaned on acidified silica gel and measured by gas chromatography coupled with electron capture negative ionization mass spectrometry (GC-ECNI-MS), while fraction B containing PFRs was directly analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). This approach resulted in recoveries between 81–120 % for PBDEs and 75–113 % for PFRs (relative standard deviation (RSD)?n?=?9). The optimized multi-residue method has been applied to 20 human hair samples. The obtained results indicated that the levels of PBDEs in hair samples were very low (0.2–12 ng/g) in relation to PBDE levels in human hair samples from other studies and most of the time below the method limit of quantification (LOQ_m). On the contrary, the PFR levels were relatively high as they were in the range of the levels previously found in dust samples (2–5,032 ng/g hair). We would like to highlight that the contribution of air and dust cannot be neglected (especially in the case of PFRs); therefore, we suggest that hair might be a good indicator of retrospective and integral exposure (which includes atmospheric deposition as well as endogenous mechanisms). Moreover, the aim of our study is focused on exposure assessment and levels detected in hair (independently of whether they come from internal or external exposure) and will significantly contribute to the exposure assessment. Graphical abstract

Hair - an efficient way for sampling of personal cloud of exposure. Copyright ©2014 iStockphoto LP     

Generic positivity and foliations in positive characteristic

We prove generic semipositivity of the tangent bundle of a non-uniruled Calabi–Yau variety in positive characteristic. We also construct an example of a nef line bundle in characteristic zero, whose each reduction to positive characteristic is not nef.     

A Short Synthesis of Fusaric Acid and Analogues

Fusaric acid (5-n-butyl-pyridine-2-carboxylic acid) and other substituted picolinic acid derivatives are synthesized in two steps from readily available α,β-unsaturated hydrazones and 2-chloroacrylonitrile in high yield.     

Synthesis and Structural Analysis of Some Podands with C3 Symmetry

Abstract

The multistep syntheses of C₃-symmetrical tripodands with terminal triple bonds or azide groups exhibiting 1,3,5-triarylbenzene and 2,4,6-triaryl-1,3,5-triazine cores are reported herein. The structures of the newly synthesized compounds are supported by NMR investigations.     

SIMS sputtering rates in biogenic aragonite: implications for culture calibration studies for palaeoenvironmental reconstruction

We used scanning white light interferometry to view the craters produced during secondary ion mass spectrometry (SIMS) analysis of the CaCO₃ skeleton of an aragonitic coral. The dimensions and volumes of craters sputtered during trace element, δ¹⁸O, δ¹³C and δ¹¹B analyses were determined. Sputtering rates were ~6 µm³ nA^?1 min^?1 for a ¹⁶O^? primary beam and ranged from ~12 µm³ nA^?1 min^?1 (for δ¹⁸O analyses) to ~19 µm³ nA^?1 (for δ¹³C analyses) using a Cs⁺ primary beam. Sputter yields (atoms sputtered/impinging primary ions) ranged from 1.3 to 1.4 for a ¹⁶O^? primary beam and from 2.5 to 4.5 using a Cs⁺ primary beam. Useful ion yields (ions detected/atoms sputtered), using instrument conditions typically used in geoscience applications, were of the order of 10^?4 for B, Mg, Ca, Sr, Ba and C and 10^?2 for O. The maximum lengths of the SIMS craters, at the sample surface, range from ~17 µm (δ¹³C analyses) to ~36 µm (δ¹¹B analyses) and crater depths range from ≤3 µm (δ¹⁸O analyses) to >20 µm (δ¹¹B analyses). These dimensions are significant in relation to accretion rates in a range of biogenic carbonates and SIMS analyses typically sample carbonate deposited over time periods of days to months depending on the organism and structure analysed. In culture calibration studies, accurate determination of the temporal resolution of the analysed volume is crucial to ensure that the entire volume reflects the culture conditions and does not include carbonate deposited prior to introduction of the organism to the culture system. Copyright © 2013 John Wiley & Sons, Ltd.     

Quadrupole‐time‐of‐flight mass spectrometry screening for synthetic cannabinoids in herbal blends

‘Legal highs’ are novel substances which are intended to elicit a psychoactive response. They are sold from ‘head shops’, the internet and from street suppliers and may be possessed without legal restriction. Several months ago, a 19‐year‐old woman came searching for medical treatment as she had health problems caused by smoking legal highs. The substances were sold as herbal blends in plastic bags under four different labels. In this work, samples of these herbal blends have been analysed to investigate the presence of psychoactive substances without any reference standard being available at the laboratory. A screening strategy for a large number of synthetic and natural cannabinoids has been applied based on the use of ultra‐high pressure liquid chromatography coupled to quadrupole‐time of flight mass spectrometry (UHPLC‐QTOF MS) under MS^E mode. A customized home‐made database containing literature‐based exact masses for parent and product ions of around 200 synthetic and natural cannabinoids was compiled. The presence of the (de)protonated molecule measured at its accurate mass was evaluated in the samples. When a peak was detected, collision‐induced dissociation fragments and characteristic isotopic ions were also evaluated and used for tentative identification. After this tentative identification, four synthetic cannabinoids (JWH‐081, JWH‐250, JWH‐203 and JWH‐019) were unequivocally confirmed by subsequent acquisition of reference standards. The presence in the herbal blends of these synthetic cannabinoids might explain the psychotic and catatonic symptoms observed in the patient, as JWH compounds could act as potent agonists of CB₁ and CB₂ receptors located in the Limbic System and Basal ganglia of the human brain. Copyright © 2013 John Wiley & Sons, Ltd.     

A Planar,Conjugated N4‐Macrocyclic Cobalt Complex for Heterogeneous Electrocatalytic CO2 Reduction with High Activity

Metal complexes have been widely investigated as promising electrocatalysts for CO₂ reduction. Most of the current research efforts focus mainly on ligands based on pyrrole subunits, and the reported activities are still far from satisfactory. A novel planar and conjugated N₄‐macrocyclic cobalt complex (Co(II)CPY) derived from phenanthroline subunits is prepared herein, and it delivers high activity for heterogeneous CO₂ electrocatalysis to CO in aqueous media, and outperforms most of the metal complexes reported so far. At a molar loading of 5.93×10^?8 mol cm^?2, it exhibits a Faradaic efficiency of 96 % and a turnover frequency of 9.59 s^?1 towards CO at ?0.70 V vs. RHE. The unraveling of electronic structural features suggests that a synergistic effect between the ligand and cobalt in Co(II)CPY plays a critical role in boosting its activity. As a result, the free energy difference for the formation of *COOH is lower than that with cobalt porphyrin, thus leading to enhanced CO production.     

Crystallographic evidence for unintended benzisothiazolinone 1‐oxide formation from benzothiazinones through oxidation

1,3‐Benzothiazin‐4‐ones (BTZs) are a promising new class of drugs with activity against Mycobacterium tuberculosis, which have already reached clinical trials. A product obtained in low yield upon treatment of 8‐nitro‐2‐(piperidin‐1‐yl)‐6‐(trifluoromethyl)‐4H‐benzothiazin‐4‐one with 3‐chloroperbenzoic acid, in analogy to a literature report describing the formation of sulfoxide and sulfone derived from BTZ043 [Tiwari et al. (2015). ACS Med. Chem. Lett. 6 , 128–133], is a ring‐contracted benzisothiazolinone (BIT) 1‐oxide, namely, 7‐nitro‐2‐(piperidine‐1‐carbonyl)‐5‐(trifluoromethyl)benzo[d]isothiazol‐3(2H)‐one 1‐oxide, C₁₄H₁₂F₃N₃O₅S, as revealed by X‐ray crystallography. Single‐crystal X‐ray analysis of the oxidation product originally assigned as BTZ043 sulfone provides clear evidence that the structure of the purported BTZ043 sulfone is likewise the corresponding BIT 1‐oxide, namely, 2‐[(S)‐2‐methyl‐1,4‐dioxa‐8‐azaspiro[4.5]decane‐8‐carbonyl]‐7‐nitro‐5‐(trifluoromethyl)benzo[d]isothiazol‐3(2H)‐one 1‐oxide, C₁₇H₁₆F₃N₃O₇S. A possible mechanism for the ring contraction affording the BIT 1‐oxides instead of the anticipated constitutionally isomeric BTZ sulfones and antimycobacterial activities thereof are discussed.