Identification of inorganic ions in post‐blast explosive residues using portable CE instrumentation and capacitively coupled contactless conductivity detection

Novel CE methods have been developed on portable instrumentation adapted to accommodate a capacitively coupled contactless conductivity detector for the separation and sensitive detection of inorganic anions and cations in post‐blast explosive residues from homemade inorganic explosive devices. The methods presented combine sensitivity and speed of analysis for the wide range of inorganic ions used in this study. Separate methods were employed for the separation of anions and cations. The anion separation method utilised a low conductivity 70 mM Tris/70 mM CHES aqueous electrolyte (pH 8.6) with a 90 cm capillary coated with hexadimethrine bromide to reverse the EOF. Fifteen anions could be baseline separated in 7 min with detection limits in the range 27–240 μg/L. A selection of ten anions deemed most important in this application could be separated in 45 s on a shorter capillary (30.6 cm) using the same electrolyte. The cation separation method was performed on a 73 cm length of fused‐silica capillary using an electrolyte system composed of 10 mM histidine and 50 mM acetic acid, at pH 4.2. The addition of the complexants, 1 mM hydroxyisobutyric acid and 0.7 mM 18‐crown‐6 ether, enhanced selectivity and allowed the separation of eleven inorganic cations in under 7 min with detection limits in the range 31–240 μg/L. The developed methods were successfully field tested on post‐blast residues obtained from the controlled detonation of homemade explosive devices. Results were verified using ion chromatographic analyses of the same samples.     

Quantification of appetite suppressing steroid glycosides from Hoodia gordonii in dried plant material, purified extracts and food products using HPLC-UV and HPLC-MS methods

High-performance liquid chromatography (HPLC)-UV and HPLC-Mass Spectrometry (MS) methods were developed for the quantitative analysis of the family of Hoodia gordonii steroid glycosides with appetite suppressing properties in dried plant material, in purified and enriched extracts and in various prototype food-products fortified with H. gordonii extracts. For solid materials, e.g. dried plants or for non-fatty foods, extraction of the steroid glycosides is performed using methanol. For products where the steroid glycosides are present in an oil matrix, direct injection of the oil after dilution in tetrahydrofuran is applied. The HPLC separation is performed on an octyl-modified reversed-phase column in the gradient mode with UV detection at lambda = 220 nm. Quantification is performed against an external calibration line prepared using either one of the pure steroid glycosides or geranyl-tiglate. Short- and long-term repeatabilities of the methods are better than 3 and 6%, respectively. Recoveries are better than 85%, even in the analysis of the least abundant steroid glycosides in a complex yoghurt drink. Linearity is better than 3-4 orders of magnitude and the detection limits are below approximately 2 microg g(-1) for the individual steroid glycosides in dried plant material and food products. HPLC-MS is used to confirm that the steroid glycosides contain the characteristic steroid core, the carbohydrate chain and the tigloyl group.     

Hamiltonian replica exchange molecular dynamics using soft-core interactions

To overcome the problem of insufficient conformational sampling within biomolecular simulations, we have developed a novel Hamiltonian replica exchange molecular dynamics (H-REMD) scheme that uses soft-core interactions between those parts of the system that contribute most to high energy barriers. The advantage of this approach over other H-REMD schemes is the possibility to use a relatively small number of replicas with locally larger differences between the individual Hamiltonians. Because soft-core potentials are almost the same as regular ones at longer distances, most of the interactions between atoms of perturbed parts will only be slightly changed. Rather, the strong repulsion between atoms that are close in space, which in many cases results in high energy barriers, is weakened within higher replicas of our proposed scheme. In addition to the soft-core interactions, we proposed to include multiple replicas using the same Hamiltonian/level of softness. We have tested the new protocol on the GTP and 8-Br-GTP molecules, which are known to have high energy barriers between the anti and syn conformation of the base with respect to the sugar moiety. During two 25 ns MD simulations of both systems the transition from the more stable to the less stable (but still experimentally observed) conformation is not seen at all. Also temperature REMD over 50 replicas for 1 ns did not show any transition at room temperature. On the other hand, more than 20 of such transitions are observed in H-REMD using six replicas (at three different Hamiltonians) during 6.8 ns per replica for GTP and 12 replicas (at six different Hamiltonians) during 8.7 ns per replica for 8-Br-GTP. The large increase in sampling efficiency was obtained from an optimized H-REMD scheme involving soft-core potentials, with multiple simulations using the same level of softness. The optimization of the scheme was performed by fast mimicking [J. Hritz and C. Oostenbrink, J. Chem. Phys. 127, 204104 (2007)].     

Towards a universal product ion mass spectral library - reproducibility of product ion spectra across eleven different mass spectrometers

Product ion spectra produced by collision-induced dissociation (CID) in tandem mass spectrometry experiments can differ markedly between instruments. There have been a number of attempts to standardise the production of product ion spectra; however, a consensus on the most appropriate approach to the reproducible production of spectra has yet to be reached. We have previously reported the comparison of product ion spectra on a number of different types of instruments - a triple quadrupole, two ion traps and a Fourier transform ion cyclotron resonance mass spectrometer (Bristow AWT, Webb KS, Lubben AT, Halket JM. Rapid Commun. Mass Spectrom. 2004; 18: 1). The study showed that a high degree of reproducibility was achievable. The goal of this study was to improve the comparability and reproducibility of CID product ion mass spectra produced in different laboratories and using different instruments. This was carried out experimentally by defining a spectral calibration point on each mass spectrometer for product ion formation. The long-term goal is the development of a universal (instrument independent) product ion mass spectral library for the identification of unknowns.The spectra of 48 compounds have been recorded on eleven mass spectrometers: six ion traps, two triple quadrupoles, a hybrid triple quadrupole, and two quadrupole time-of-flight instruments. Initially, 4371 spectral comparisons were carried out using the data from eleven instruments and the degree of reproducibility was evaluated. A blind trial has also been carried out to assess the reproducibility of spectra obtained during LC/MS/MS.The results suggest a degree of reproducibility across all instrument types using the tuning point technique. The reproducibility of the product ion spectra is increased when comparing the tandem in time type instruments and the tandem in space instruments as two separate groups. This may allow the production of a more limited, yet useful, screening library for LC/MS/MS identification using instruments of the same type from different manufacturers.     

Coupling Microdroplet Microreactors with Mass Spectrometry: Reading the Contents of Single Droplets Online

Fully integrated : Mass spectrometry has been integrated into a detection scheme for microdroplets that are created within microfluidic channels (see picture, scale bar 200 μm). This technique allows droplets to be identified based on the compounds they contain, and combines fluorescence screening with MS analysis. These experiments indicate how similar approaches can be applied to the ambitious goals of on‐chip protein evolution and chemical synthesis.

     

CE-LIF coupled with flow cytometry for high-throughput quantitation of fluorophores in single intact cells

We report a method of coupled CE-LIF detection with flow cytometry for high-throughput determination and quantitation of fluorophores in single intact K562/S (KS) cells. The membrane properties of KS cell including fluophore transport rate and apparent permeability coefficient were further quantitatively characterized. The method has advantages for accurate quantitation and unique capacity of high-throughput analysis. The strategy will be useful for the quantitation of fluorophores in the intact cells, such as measurement of multidrug resistance, quantitation of specific protein expression, and quantitative characterization of protein and enzyme functions.     

Synthesis and stereochemistry of some novel dihydropyrrolo[3,4-c]pyrazoles

Abstract  

Eleven novel dihydropyrrolo[3,4-c]pyrazole derivatives were obtained by the reaction of chiral (1R)-N-(1-phenylethyl)maleimide and C,N-aryl-substituted nitrilimines. The reaction afforded the cycloadducts as a regioisomeric mixture which can be separable in some cases. The structure and stereochemistry of cycloadducts were assigned on the basis of infrared (IR), ¹H and ¹³C nuclear magnetic resonance (NMR), mass and X-ray spectra, optical rotation measurements, and CHN analyses.     

高效液相色谱/氢化物发生/原子荧光快速检测尿砷形态

本文对砷形态分析方法进行了评述。提出了人尿中Ａｓ（Ⅲ）、Ａｓ（Ⅴ）、一甲基砷（ＭＭＡ）和二甲基砷（ＤＭＡ）的快速、灵敏的形态分析方法。方法基于在１５ｃｍ长、３μｍ粒径的ＨＰＬＣ柱上快速分离不同形态的砷后以灵敏的氢化物发生／原子荧光检测。常见砷的四种形态的分析只须４ｍｉｎ即可完成,检出限在μｇ／Ｌ级。标准样品尿中砷的形态分析结果与标准值吻合很好。本法已应用于摄取砷糖前、后所采集的尿样中砷的形态分析研     

A genetic algorithm for the structural optimization of Morse clusters

This article describes the application of a genetic algorithm for the structural optimization of 19–50-atom clusters bound by medium-range and short-range Morse pair potentials. The GA is found to be efficient and reliable for finding the geometries corresponding to the previously published global minima [Doye JPK, Wales DJ (1997) J Chem Soc Faraday Trans 93: 4233]. Using the genetic algorithm, only a relatively small number of energy evaluations and minimizations are required to find the global minima. By contrast, a simple random search algorithm often cannot find the global minima of the larger clusters, even after many thousands of searches. Received: 27 October 1999 / Accepted: 7 December 1999 / Published online: 19 April 2000