41 research outputs found
Postcolumn derivatization liquid chromatography/mass spectrometry for detection of chemical-weapons-related compounds
AbstractPostcolumn derivatization for liquid chromatography/mass spectrometry (LC/MS) analysis was characterized for detection of some compounds related to chemical-weapons (CW) agents using an Atmospheric Pressure Chemical Ionization (APCI) source. The derivatizing reagents were added directly to the LC eluent flow, and the derivatization reactions occurred in the APCI source under typical operating conditions. The compound S-[2-(diisopropylamino)ethyl] methylphosphonothioic acid was methylated using the derivatizing reagent trimethylphenyl ammonium hydroxide (TMPAH). Methylphosphonic acid was doubly derivatized to form dimethyl methylphosphonate, although the signal for the derivatization product was very sensitive to the amount of TMPAH. Arsenic compounds related to the CW agent lewisite, including chlorovinyl arsonous acid and arsenic (III) oxide, were derivatized using 2-mercaptopyridine. The thiol group reacted readily with the arsenic (III) center and provided a significant improvement in sensitivity relative to the underivatized signal using APCI or electrospray ionization. Triethanolamine and ethyl diethanolamine were derivatized with benzoyl chloride, a commonly used LC derivatizing reagent for alcohols, to modify their mass spectra. Postcolumn derivatization using an APCI source gives an alternative for detecting some difficult-to-ionize compounds. It has the limitations that sensitivity was not always improved even though the major mass spectral peaks can be shifted; it is necessary to carefully select the reagent; and some reagents introduced strong interference peaks at specific masses in the spectrum and may suppress the ionization of some derivatized analyte ions. The reagent also produced contamination in the source, which had to be cleaned daily
Communications Biophysics
Contains reports on four research projects.U.S. Air Force under Contract AF19(604)-411
Recommended from our members
Nerve Agent Degradation Using Polyoxoniobates
Polyoxoniobates are exceptional amongst polyoxometalates in that
they can potentially perform base catalysis in water, a process in
which a proton is bonded to an oxo ligand, and a hydroxyl is
released. Catalytic decomposition of chemical warfare agents such
as organofluorophosphates that were used recently in the infamous
civilian attacks in Syria is one opportunity to employ this process.
Upon evaluation of the polyoxoniobate Lindqvist ion, [NbâOââ]âžâ»
fast neutralization kinetics was discovered for the breakdown of the
nerve agent simulant diisopropyl fluorophosphate (DFP). Further
testing of the polyoxoniobates against nerve agents Sarin (GB), and
Soman (GD) was also performed. It was determined that different
Lindqvist countercations (Li, K, or Cs) affect the rate of decomposition of the organophosphate
compounds in both aqueous media (homogeneous reaction), and
in the solid-state (heterogeneous reaction). Small-angle X-ray
scattering of solutions of the Li, K, and Cs [NbâOââ]âžâ» salts at
concentrations which the experiments were performed revealed
distinct differences that could be linked to their relative reaction
rates. This study represents the first demonstration of exploiting
the unique alkaline reactivity of polyoxoniobates for nerve agent
decontamination.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Wiley-VCH and can be found at: http://onlinelibrary.wiley.com/doi/10.1002/ejic.201400016/full.Keywords: Nerve agents, Small-angle X-ray scattering, Kinetics, Polyoxometalates, Ion pair
A framework for human microbiome research
A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies
Structure, function and diversity of the healthy human microbiome
Author Posting. © The Authors, 2012. This article is posted here by permission of Nature Publishing Group. The definitive version was published in Nature 486 (2012): 207-214, doi:10.1038/nature11234.Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitatâs signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81â99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.This research was supported in
part by National Institutes of Health grants U54HG004969 to B.W.B.; U54HG003273
to R.A.G.; U54HG004973 to R.A.G., S.K.H. and J.F.P.; U54HG003067 to E.S.Lander;
U54AI084844 to K.E.N.; N01AI30071 to R.L.Strausberg; U54HG004968 to G.M.W.;
U01HG004866 to O.R.W.; U54HG003079 to R.K.W.; R01HG005969 to C.H.;
R01HG004872 to R.K.; R01HG004885 to M.P.; R01HG005975 to P.D.S.;
R01HG004908 to Y.Y.; R01HG004900 to M.K.Cho and P. Sankar; R01HG005171 to
D.E.H.; R01HG004853 to A.L.M.; R01HG004856 to R.R.; R01HG004877 to R.R.S. and
R.F.; R01HG005172 to P. Spicer.; R01HG004857 to M.P.; R01HG004906 to T.M.S.;
R21HG005811 to E.A.V.; M.J.B. was supported by UH2AR057506; G.A.B. was
supported by UH2AI083263 and UH3AI083263 (G.A.B., C. N. Cornelissen, L. K. Eaves
and J. F. Strauss); S.M.H. was supported by UH3DK083993 (V. B. Young, E. B. Chang,
F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K.P.R. was supported by UH2DK083990 (J.
V.); J.A.S. and H.H.K. were supported by UH2AR057504 and UH3AR057504 (J.A.S.);
DP2OD001500 to K.M.A.; N01HG62088 to the Coriell Institute for Medical Research;
U01DE016937 to F.E.D.; S.K.H. was supported by RC1DE0202098 and
R01DE021574 (S.K.H. and H. Li); J.I. was supported by R21CA139193 (J.I. and
D. S. Michaud); K.P.L. was supported by P30DE020751 (D. J. Smith); Army Research
Office grant W911NF-11-1-0473 to C.H.; National Science Foundation grants NSF
DBI-1053486 to C.H. and NSF IIS-0812111 to M.P.; The Office of Science of the US
Department of Energy under Contract No. DE-AC02-05CH11231 for P.S. C.; LANL
Laboratory-Directed Research and Development grant 20100034DR and the US
Defense Threat Reduction Agency grants B104153I and B084531I to P.S.C.; Research
Foundation - Flanders (FWO) grant to K.F. and J.Raes; R.K. is an HHMI Early Career
Scientist; Gordon&BettyMoore Foundation funding and institutional funding fromthe
J. David Gladstone Institutes to K.S.P.; A.M.S. was supported by fellowships provided by
the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial
Pathogenesis Training Grant T32AI007528; a Crohnâs and Colitis Foundation of
Canada Grant in Aid of Research to E.A.V.; 2010 IBM Faculty Award to K.C.W.; analysis
of the HMPdata was performed using National Energy Research Scientific Computing
resources, the BluBioU Computational Resource at Rice University
A multimodal cell census and atlas of the mammalian primary motor cortex
ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties
Reaction of Nerve Agents with Phosphate Buffer at pH 7
Chemical weapon nerve agents, including isopropyl methylphosphonofluoridate
(GB or Sarin), pinacolyl methylphosphonofluoridate (GD or Soman),
and <i>S</i>-(2-diisopropylaminoethyl) <i>O</i>-ethyl methylphosphonothioate (VX), are slow to react in aqueous
solutions at midrange pH levels. The nerve agent reactivity increases
in phosphate buffer at pH 7, relative to distilled water or acetate
buffer. Reactions were studied using <sup>31</sup>P NMR. Phosphate
causes faster reaction to the corresponding alkyl methylphosphonic
acids, and produces a mixed phosphate/phosphonate compound as an intermediate
reaction product. GB has the fastest reaction rate, with a bimolecular
rate constant of 4.6 Ă 10<sup>â3</sup> M<sup>â1</sup>s<sup>â1</sup>[PO<sub>4</sub><sup>3â</sup>]. The molar
product branching ratio of GB acid to the pyro product (isopropyl
methylphosphonate phosphate anhydride) is 1:1.4, independent of phosphate
concentration, and the pyro product continues to react much slower
to form GB acid. The pyro product has two doublets in the <sup>31</sup>P NMR spectrum. The rate of reaction for GD is slower than GB, with
a rate constant of 1.26 Ă 10<sup>â3</sup> M<sup>â1</sup>s<sup>â1</sup> [PO<sub>4</sub><sup>3â</sup>]. The rate
for VX is considerably slower, with a rate constant of 1.39 Ă
10<sup>â5</sup> M<sup>â1</sup>s<sup>â1</sup> [PO<sub>4</sub><sup>3â</sup>], about 2 orders of magnitude slower
than the rate for GD. The rate constant of the reaction of GD with
pyrophosphate at pH 8 is 2.04 Ă 10<sup>â3</sup> min<sup>â1</sup> at a concentration of 0.0145 M. The rate of reaction
for diisopropyl fluorophosphate is 2.84 Ă 10<sup>â3</sup> min<sup>â1</sup> at a concentration of 0.153 M phosphate,
a factor of 4 slower than GD and a factor of 15 slower than GB, and
there is no detectable pyro product. The half-lives of secondary reaction
of the GB pyro product in 0.153 and 0.046 M solution of phosphate
are 23.8 and 28.0 h, respectively, which indicates little or no dependence
on phosphate
Further Studies into the Feasibility of Using Aqueous Alum Solutions in the Destruction of VX
The destruction of phosphorus based chemical warfare agents using aqueous buffer mixtures of aluminum sulfate (alum) and sodium aluminate is pursued. The production of VX (O-ethyl-S-[2-(diisopropylamino)ethyl]-methylphos-phonothiolate) hydrolysis products ethyl methyl phosphonic acid (EMPA), an aluminum complex of EMPA, and S-[2-(diisopropylamino)ethyl]methylphosphonothiolate (EA-2192) is characterized in acidic and basic alum buffers. The study employs ^{31}P high resolution magic angle nuclear magnetic resonance spectroscopy (HRMAS NMR) for both quantitative and qualitative analysis. The acidic buffer results in a slower reaction rate and is less effective than the basic buffer
Aluminum Sulfate and Sodium Aluminate Buffer Solutions for the Destruction of Phosphorus Based Chemical Warfare Agents
Nerve agents VX and GB (sarin) are sequestered and removed by aluminum sulfate and sodium aluminate mixts. adjusted to pH 4 in soln. The products of hydrolysis are removed with the alum floc below NMR detection limits over time depending and the amt. of aluminum molar excess relative to agent. Half-lives for GB decompn. are 3.1 h and 1.1 h, resp., for a 120 and a 1200 M excess. For VX, the half-lives are 8.5 d and 2.9 d for a 240 and a 5000 M aluminum excess. In the case of GB, fluorine is sequestered as the hexafluoroaluminate ion. In the case of VX, no phosphorus contg. hydrolysis products including the very toxic S-[2-(diisopropyl-amino)-ethyl]methylphosphonothiolate (EA-2192) are detected in the hydrolyzate