Copper and iron interactions with angiotensin-converting enzyme inhibitors. A study by fast-atom bombardment tandem mass spectrometry

Fast atom bombardment, combined with high-energy collision-induced tandem mass spectrometry, has been used to investigate gas-phase metal-ion interactions with captopril, enalaprilat and lisinopril, all angiotensin-converting enzyme inhibitors.Suggestions for the location of metal-binding sites are presented. For captopril, metal binding occurs most likely at both the sulphur and the nitrogen atom. For enalaprilat and lisinopril, binding preferably occurs at the amine nitrogen. Copyright 1999 John Wiley & Sons, Ltd.     

Analysis of chemical warfare agents. I. Use of aliphatic thiols in the trace level determination of Lewisite compounds in complex matrices

A series of normal aliphatic thiols have been used to derivatise the chemical warfare agents Lewisites I and II (LI and LII) in hydrocarbon matrices. Varying the chain length of the thiol allowed adjustment of derivative tR by 5.9 min for Lewisite I and 5.3 min for Lewisite II. Linear regression analysis of the chain length of the thiol derivatives of the Lewisite species, and that of a series of normal alkanes against tR, allowed regression models to be developed for each set of compounds. Application of the models allowed thiol reagents to be chosen to give derivatives of Lewisites I and II that eluted before and after the major hydrocarbon contaminant. Limits of detection were comparable for all thiol derivatives analysed by GC-MS in the selection ion monitoring mode (all below 1 microg ml(-1)). The robustness of this approach was illustrated by successful identification of Lewisite I in samples from the Sixth Proficiency Test (organised by the Organisation for the Prohibition of Chemical Weapons, OPCW) in a matrix of 1 mg ml(-1) diesel oil.     

Hydrolysis and Oxidation Products of the Chemical Warfare Agents 1,2-Bis[(2-chloroethyl)thio]ethane Q and 2,2′-Bis(2-chloroethylthio)diethyl Ether T

Syntheses of diols of structure [HOCH₂CH₂S]₂(CH₂)_n in 86–95% yield from the sodium salt of 2-mercaptoethanol and Br(CH₂)_nBr (n = 1 to 5) or in 60–90% yield from 2-chloroethanol and NaS(CH₂)_nSNa (n = 2 to 5) are described. The diol [HOCH₂CH₂SCH₂CH₂]₂O was prepared in 82% yield from the sodium salt of 2-mercaptoethanol and [ClCH₂CH₂]₂O, and in 88% yield from 2-chloroethanol and [HSCH₂CH₂]₂O. Mono- and bis-sulfoxides and bis-sulfones of these species were prepared in generally high yield by treatment with an equivalent of KIO₄ in aqueous methanol, two equivalents of NaIO₄ in aqueous methanol, or four equivalents of H₂O₂ in trifluoroacetic acid respectively. The compounds are important analytical standards for investigating the fate of the chemical warfare agents sesquimustard Q and oxygen mustard T in environmental samples.     

CONCERNING THE ORIGIN OF CHARGE AT THE POLYSTYRENE PARTICLE/WATER INTERFACE

The electrophoretic mobility behavior of well-characterized polystyrene latex particles, carrying one type of surface functional endgroups, has been studied as a function of pH. At low pH, the interaction of protons with the functional endgroups increased in the order: Hydroxyl > carboxyl > sulfate; at high pH the order of interaction was reversed; and at intermediate pH no interactions were observed. The particles of the polystyrene latexes in their different forms at the intermediate pH range, dispersed in deionized water, all exhibited the same mobility irrespective of the functional endgroup. The origin of charge in these systems is explained as being the result of either the preferential adsorption of hydroxyl ions or an electron - injection mechanism due to the overlap of local intrinsic molecular - ion states in polystyrene and water. At low concentrations of functional endgroups, the surface properties of the polystyrene latexes are largely dependent upon the hydrophobic nature of the surface.     

Chemical analysis of bleach and hydroxide-based solutions after decontamination of the chemical warfare agent O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate (VX)

Detailed chemical analysis of solutions used to decontaminate chemical warfare agents can be used to support verification and forensic attribution. Decontamination solutions are amongst the most difficult matrices for chemical analysis because of their corrosive and potentially emulsion-based nature. Consequently, there are relatively few publications that report their detailed chemical analysis. This paper describes the application of modern analytical techniques to the analysis of decontamination solutions following decontamination of the chemical warfare agent O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate (VX). We confirm the formation of N,N-diisopropylformamide and N,N-diisopropylamine following decontamination of VX with hypochlorite-based solution, whereas they were not detected in extracts of hydroxide-based decontamination solutions by nuclear magnetic resonance (NMR) spectroscopy or gas chromatography-mass spectrometry. We report the electron ionisation and chemical ionisation mass spectroscopic details, retention indices, and NMR spectra of N,N-diisopropylformamide and N,N-diisopropylamine, as well as analytical methods suitable for their analysis and identification in solvent extracts and decontamination residues.     

Both systemic and local application of Granulocyte-colony stimulating factor (G-CSF) is neuroprotective after retinal ganglion cell axotomy

Background  

The hematopoietic Granulocyte-Colony Stimulating Factor (G-CSF) plays a crucial role in controlling the number of neutrophil progenitor cells. Its function is mediated via the G-CSF receptor, which was recently found to be expressed also in the central nervous system. In addition, G-CSF provided neuroprotection in models of neuronal cell death. Here we used the retinal ganglion cell (RGC) axotomy model to compare effects of local and systemic application of neuroprotective molecules.     

Analysis of chemical warfare agents. II. Use of thiols and statistical experimental design for the trace level determination of vesicant compounds in air samples

Thermal desorption with gas chromatography-mass spectrometry (TD-GC-MS) remains the technique of choice for analysis of trace concentrations of analytes in air samples. This paper describes the development and application of a method for analysing the vesicant compounds sulfur mustard and Lewisites I-III. 3,4-Dimercaptotoluene and butanethiol were used to spike sorbent tubes and vesicant vapours sampled; Lewisite I and II reacted with the thiols while sulfur mustard and Lewisite III did not. Statistical experimental design was used to optimise thermal desorption parameters and the optimum method used to determine vesicant compounds in headspace samples taken from a decontamination trial. 3,4-Dimercaptotoluene reacted with Lewisites I and II to give a common derivative with a limit of detection (LOD) of 260 microg m(-3), while the butanethiol gave distinct derivatives with limits of detection around 30 microg m(-3).     

Analysis of chemical warfare agents III. Use of bis-nucleophiles in the trace level determination of phosgene and perfluoroisobutylene

The reactivity of phosgene and perfluoroisobutylene (PFIB) towards 1,2-bis-nucleophiles was exploited to allow determination of these gases in air samples. 2-Aminothiophenol (ATP), 3,4-dimercaptotoluene (DMT) and 2-hydroxymethylpiperidine (HMP) were evaluated as bis-nucleophiles capable of forming thermally-stable derivatives with phosgene and PFIB when loaded with triethylamine onto Tenax TA. Experimental design was used to optimise thermal desorption conditions. Detection limits in the low ngm(-3) range were observed for the five derivatives investigated. This work represents the most sensitive analytical method for trace level quantitation of phosgene and PFIB published to date.