- Mass spectral studies of silyl derivatives of partially hydrolyzed products of nitrogen mustards: Important markers of nitrogen mustard exposure
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Rationale: Nitrogen mustards (NMs) are vesicant class of chemical warfare agents. From the viewpoint of the Chemical Weapons Convention partially hydrolyzed products of nitrogen mustards (pHpNMs) are considered as important markers of nitrogen mustard exposure. The detection of pHpNMs from biological or environmental samples is highly useful for obtaining forensic evidence of exposure to NMs. Methods: Gas chromatography interfaced with tandem mass spectrometry (GC/MS/MS) is a widely used tool for the identification and sensitive detection of metabolites of NMs in complex matrices. The pHpNMs were derivatized using silylating agents as they are highly polar and non-amenable to GC. The mass spectral studies of these silyl derivatives of pHpNMs were performed using GC/MS/MS in both electron ionization (EI) and chemical ionization (CI) mode. Results: Various approaches have been proposed to assess the fragmentation pathways of the trimethylsilyl (TMS) and tert-butyldimethylsilyl (TBDMS) derivatives of pHpNMs. All the proposed fragmentation pathways were based on the product and/or precursor ion scanning of corresponding ions in both EI and CI mode. In the case of EI, most of the fragmentation pathways involved either α-cleavage or inductive cleavage. Conclusions: This is the first report on the MS study of the silyl derivatives of pHpNMs. The study of the two different derivatives of pHpNMs using both EI- and CI-MS provides a reliable, unambiguous identification of pHpNMs in complex environmental and biomedical matrices (such as plasma and urine) during any verification activities.
- Chandra, Buddhadeb,Sinha Roy, Kanchan,Shaik, Mahabul,Waghmare, Chandrakant,Palit, Meehir
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- Development of highly active anti-: Pneumocystis bisbenzamidines: Insight into the influence of selected substituents on the in vitro activity
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Here we describe the potency of 21 pentamidine analogues against the fungal pathogen, Pneumocystis carinii, in an ATP bioluminescent assay with toxicity profiles in 2 mammalian cell lines. Reduction of two 5-methyl-1,2,4-oxadiazole rings was applied to the synthesis of acid-labile bisamidines. Anti-Pneumocystis activity is discussed in the context of 3 groups of compounds depending on the main structural changes of the pentamidine lead structure. The groups include: 1) 1,4-bis(methylene)piperazine derivatives 1-5; 2) alkanediamide derivatives 6-10; 3) alkane-derived bisbenzamidines 11-21. IC50 values of 18 compounds were lower than the IC50 of pentamidine. Four bisamidines were active at nanogram concentrations. Introduction of sulfur atoms in the alkane bridge, replacement of the amidino groups with imidazoline rings, or attachment of nitro or amino groups to the benzene rings is responsible for remarkable activity of the new leading structures. The vast majority of compounds, including four highly active ones, can be classified as mild or nontoxic to host cells. These compounds show promise as candidates for new anti-Pneumocystis agents.
- Maciejewska,Zabiński,Rezler,Ka?mierczak,Collins,Ficker,Cushion
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supporting information
p. 2003 - 2011
(2017/10/27)
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- Crown Ether Annelated Tetrathiafulvalenes. 2
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A synthetic procedure leading to derivatives of tetrathiafulvalene (TTF) incorporating polyether chains of various lengths, some nitrogen analogs, and a 2,6-bis(methylene)pyridine analog has been developed.These compounds possess cage-type structures which were confirmed by X-ray crystallography in four cases, two of which are reported herein for the first time.Structural and electronic features of these cage molecules were correlated to oxidation potentials by the use of semiempirical methods (MNDO-PM3).An investigation of the alkali metal ion affinity using PDMS revealed that these compounds are poor ligands.Finally, in one case, protonation of the core TTF was studied by NMR.
- Hansen, T. K.,Joergensen, T.,Jensen, F.,Thygesen, P. H.,Christiansen, K.,et al.
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p. 1359 - 1366
(2007/10/02)
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