Sample records for diisopentyl methylphosphonate

  1. Developmental Toxicology of Methylphosphonic Difluoride (DF)


    Methylphosphonic Difluoride Teratogenesis Dams DP Does Acce-Icp For NTIS CRA•d UIC SASI 2 ................ .0{ I ’J ’• , /. ;. ’ UNLAS FEi ut? iAS~CAgNO ?ISPO...organogenesis period of their pregnancies . For the rat, this period was from day 6 to day 15 of gestation; for the rabbit, it was from day 6 to day 18...are so great that a person would readily leave the contaminated area. Any irritation experienced by 3the dams would have caused stress, and the 10.0

  2. Enzymic synthesis of oligonucleotides containing methylphosphonate internucleotide linkages.

    Higuchi, H; Endo, T; Kaji, A


    Thymidine 5'-O-(pyrophosphoryl methylphosphonate) (dTTP alpha CH3) has been chemically synthesized by condensation of thymidine 5'-O-(methylphosphonate) with pyrophosphate. This novel nucleotide, which contained an alpha-phosphorus atom as methylphosphonate, was used as a substrate of terminal deoxynucleotidyltransferase (TDTase) in the presence of oligonucleotide (5'-GCTGTATCGTCAAGGCACTC-3') as an initiator. The reaction products were separated into two components by reverse-phase high-performance liquid chromatography (RP-HPLC). These products were, after purification, digested with nuclease P1 and alkaline phosphatase followed by separation of digested products by RP-HPLC. The result showed the presence of one of the isomers of 2'-deoxycytidyl-3'-methylphosphonyl-5'-thymidine (dCpCH3T) and 2'-deoxycytidyl-3'-methylphosphonyl-5'-thymidyl-3'-methyl phosphonyl-5'-thymidin e (dCpCH3TpCH3T), respectively. Fast atom bombardment mass spectrometry of these products further supported identification of the dinucleotide and the trinucleotide. These results indicated that dTTP alpha CH3 was used as a substrate of TDTase, resulting in methylphosphonate linkages. Produced oligomers were resistant to hydrolysis by snake venom phosphodiesterase I.

  3. Hydrophilic interaction liquid chromatography-tandem mass spectrometry methylphosponic and alkyl methylphosphonic acids determination in environmental samples after pre-column derivatization with p-bromophenacyl bromide.

    Baygildiev, T M; Rodin, I A; Stavrianidi, A N; Braun, A V; Lebedev, A T; Rybalchenko, I V; Shpigun, O A


    Once exposed to the environment organophosphate nerve agents readily degrade by rapid hydrolysis to the corresponding alkyl methylphosphonic acids which do not exist in nature. These alkyl methylphosphonic acids are finally slowly hydrolyzed to methylphosphonic acid. Methylphosphonic acid is the most stable hydrolysis product of organophosphate nerve agents, persisting in environment for a long time. A highly sensitive method of methylphosphonic acid and alkyl methylphosphonic acids detection in dust and ground mixed samples has been developed and validated. The fact that alkyl methylphosphonic acids unlike methylphosphonic acid did not react with p-bromophenacyl bromide under chosen conditions was discovered. This allowed simultaneous chromatographic separation and mass spectrometric detection of derivatized methylphosphonic acid and underivatized alkyl methylphosphonic acids using HILIC-MS/MS method. Very simple sample pretreatment with high recoveries for each analyte was developed. Methylphosphonic acid pre-column derivate and alkyl methylphosphonic acids were detected using tandem mass spectrometry with electrospray ionization after hydrophilic interaction liquid chromatography separation. The developed approach allows achieving ultra-low detection limits: 200 pg mL(-1) for methylphosphonic acid, 70 pg mL(-1) for ethyl methylphosphonic acid, 8 pg mL(-1) for i-propyl methylphosphonic acid, 8 pg mL(-1) for i-butyl methylphosphonic acid, 5 pg mL(-1) for pinacolyl methylphosphonic acid in the extracts of dust and ground mixed samples. This approach was successfully applied to the dust and ground mixed samples from decommissioned plant for the production of chemical weapons.

  4. Adsorption of Dimethyl Methylphosphonate on MoO3

    Head, Ashley R.; Tsyshevsky, Roman; Trotochaud, Lena


    Dimethyl methylphosphonate (DMMP) is a common chemical warfare agent simulant and is widely used in adsorption studies. To further increase the understanding of DMMP interactions with metal oxides, ambient pressure X-ray photoelectron spectroscopy was used to study the adsorption of DMMP on MoO3......, including the effects of oxygen vacancies, surface hydroxyl groups, and adsorbed molecular water. Density functional theory calculations were used to aid in the interpretation of the APXPS results. An inherent lack of Lewis acid metal sites results in weak interactions of DMMP with MoO3. Adsorption...

  5. Function Discovery and Structural Characterization of a Methylphosphonate Esterase

    Xiang, Dao Feng [Texas A & M Univ., College Station, TX (United States); Patskovsky, Yury [Einstein College of Medicine, Bronx, NY (United States); Nemmara, Venkatesh V. [Texas A & M Univ., College Station, TX (United States); Toro, Rafael [Einstein College of Medicine, Bronx, NY (United States); Almo, Steven C. [Einstein College of Medicine, Bronx, NY (United States); Raushel, Frank M. [Texas A & M Univ., College Station, TX (United States)


    Pmi1525, an enzyme of unknown function from Proteus mirabilis HI4320 and the amidohydrolase superfamily, was cloned, purified to homogeneity, and functionally characterized. The three-dimensional structure of Pmi1525 was determined with zinc and cacodylate bound in the active site (PDB id: 3RHG). We also determined the structure with manganese and butyrate in the active site (PDB id: 4QSF). Pmi1525 folds as a distorted (β/α)8-barrel that is typical for members of the amidohydrolase superfamily and cog1735. Moreover, the substrate profile for Pmi1525 was determined via a strategy that marshaled the utilization of bioinformatics, structural characterization, and focused library screening. The protein was found to efficiently catalyze the hydrolysis of organophosphonate and carboxylate esters. The best substrates identified for Pmi1525 are ethyl 4-nitrophenylmethyl phosphonate (kcat and kcat /Km values of 580 s–1 and 1.2 × 105 M–1 s–1, respectively) and 4-nitrophenyl butyrate (kcat and kcat /Km values of 140 s–1 and 1.4 × 105 M–1 s–1, respectively). Pmi1525 is stereoselective for the hydrolysis of chiral methylphosphonate esters. The enzyme hydrolyzes the (SP)-enantiomer of isobutyl 4-nitrophenyl methylphosphonate 14 times faster than the corresponding (RP)-enantiomer. The catalytic properties of this enzyme make it an attractive template for the evolution of novel enzymes for the detection, destruction, and detoxification of organophosphonate nerve agents.

  6. Mid-infrared absorption spectra of dimethyl methylphosphonate as molecular simulant of nerve agents

    Yonggang Zhang; Zhenxing Cheng; Aizhen Li; Songlin Feng


    The fine mid-infrared absorption features of dimethyl methylphosphonate vapor have been characterized by using Fourier transforms infrared spectroscopy, and the nitrous oxide was used for calibration purpose. The results show that the main P-O-C and P=O bonds related absorption bands of dimethyl methylphosphonate vapor are peaked at 1050.01 and 1275.76 cm-1 respectively, those two bands show continuous characteristics at resolution of 0.125 cm-1.

  7. Energetics and Dynamics of the Reactions of O(3P) with Dimethyl Methylphosphonate and Saria


    a SN2 -like transition geometry, Figure 3c, the axial O-C-H bond angle is slightly bent more for reaction 4, Figure 3d. The products of reaction 4 are...Energetics and Dynamics of the Reactions of O(3P) with Dimethyl Methylphosphonate and Sarin Patrick F. Conforti and Matthew Braunstein* Spectral...calculations were performed on the reaction systems O(3P) + sarin and O(3P) + dimethyl methylphosphonate (DMMP), a sarin simulant. Transition state

  8. Interactions and Binding Energies of Dimethyl Methylphosphonate and Dimethyl Chlorophosphate with Amorphous Silica


    and Decomposition of Dimethyl Methylphosphonate on TiO2 . J. Phys. Chem. B 2000, 104, 12292−12298. (13) Polanyi, M.; Wigner, E. Über die Interferenz von...319, 177−184. (18) Palmero, A.; Loffler, D. G. Kinetics of Water Desorption from Pelletized 4A and 5A Zeolites. Thermochim. Acta 1990, 159, 171−176

  9. Study on Synthesis and Intercalation Behavior of Layered Zirconium Proline-N-methylphosphonate-phosphate

    Xiao Ping RAO; Xiang Kai FU; Kai RAO


    Zirconium proline-N-methylphosphonate-phosphate (α-ZPMPP) was prepared in the presence of HF for the first time. The α-ZPMPP sample is highly crystallized with interlayer distance of 1.52 nm. The interlayer distance of complex of α-ZPMPP with n-butylamine (α-ZPMPP-BA) is in 0.45 nm larger than that of α-ZPMPP. The α-ZPMPP possesses different intercalation behavior of host-guest compound from α-ZP.

  10. Catalytic Degradation of Methylphosphonic Acid Using Iron Powder/Iron Oxides


    aluminium/ aluminium oxide on the degradation of methylphosphonic acid (MPA), the final hydrolysis product of most nerve agents. EGA-FTIR provides... ALUMINIUM OXIDE ) UNDER AIR (BOTTOM). .................. 37 DSTO-TR-1849 1 1. Introduction The Convention on the Prohibition of well as aluminium/ aluminium oxide , using temperature programmed EGA-FTIR. Since MPA is a Schedule II chemical the above requirement can only be

  11. Methylphosphonic Dichloride as Reagent for the Determination of the Enantiomeric Excess of Chiral Thiols. Scope and Limitations

    Strijtveen, Bert; Kellogg, Richard M.; Feringa, Bernard


    Methylphosphonic dichloride, CH3P(=O)Cl2, reacts cleanly and quantitatively with thiols to form dialkylthiophosphonates, CH3P(=O)(SR)2. From the ratio of the integrations of the 31P absorptions in the NMR spectra, the enantiomeric excesses of the thiols can be obtained for the cases that R is chiral

  12. Rapid quantification of dimethyl methylphosphonate from activated carbon particles by static headspace gas chromatography mass spectrometry.

    Mitchell, Brendan L; Billingsley, Brit G; Logue, Brian A


    Activated carbon (AC) particles are utilized as an adsorbent for binding hazardous vapors in protective equipment. The binding affinity and utilization of these AC particles should be known to ensure effective and efficient use. Therefore, a simple and effective method was developed for the quantification of the chemical warfare agent simulant, dimethyl methylphosphonate (DMMP), from AC particles. Static headspace gas chromatography mass-spectrometry with internal standard, DMMP-d6, was used to perform the analysis. The method produced a linear dynamic range of 2.48-620g DMMP/kg carbon and a detection limit of 1.24g DMMP/kg carbon. Furthermore, the method produced a coefficient of variation of less than 16% for all intra- and inter-assay analyses. The method provided a simple and effective procedure for quantifying DMMP from AC particles and was applied to the analysis of a DMMP-exposed AC protective respirator filter.

  13. Development of kidney tumors in the male F344/N rat after treatment with dimethyl methylphosphonate.

    Dunnick, J K; Eustis, S L; Haseman, J K


    Dimethyl methylphosphonate (DMMP), a chemical that has been used as a flame retardant and as a nerve gas simulant to mimic the physical but not biologic properties of nerve gases, was administered by gavage in corn oil for up to 2 years at doses of 0, 500, or 1000 mg/kg/day to male and female F344/N rats and at doses of 0, 1000, or 2000 mg/kg/day to male and female B6C3F1 mice. Survival in dosed male rats was reduced, due in part to kidney toxicity, and lesions in the kidney included increased severity of spontaneous nephropathy, calcification, hyperplasia of the tubular and transitional epithelium, tubular cell adenocarcinomas, and transitional cell papillomas and carcinomas. Survival in female rats was similar among groups; survival in mice was reduced and this reduced survival decreased the sensitivity for detecting a carcinogenic response. There were no dose-related neoplastic responses in female rats or male or female mice. The spectrum of kidney lesions seen in the male rat given DMMP is similar to that seen after the long-term administration of a variety of other chemicals including unleaded gasoline, hydrocarbon solvents, and 1,4-dichlorobenzene.

  14. Distribution of glyphosate and methylphosphonate catabolism systems in soil bacteria Ochrobactrum anthropi and Achromobacter sp.

    Sviridov, Alexey V; Shushkova, Tatyana V; Zelenkova, Nina F; Vinokurova, Natalya G; Morgunov, Igor G; Ermakova, Inna T; Leontievsky, Alexey A


    Bacterial strains capable of utilizing methylphosphonic acid (MP) or glyphosate (GP) as the sole sources of phosphorus were isolated from soils contaminated with these organophosphonates. The strains isolated from MP-contaminated soils grew on MP and failed to grow on GP. One group of the isolates from GP-contaminated soils grew only on MP, while the other one grew on MP and GP. Strains Achromobacter sp. MPS 12 (VKM B-2694), MP degraders group, and Ochrobactrum anthropi GPK 3 (VKM B-2554D), GP degraders group, demonstrated the best degradative capabilities towards MP and GP, respectively, and were studied for the distribution of their organophosphonate catabolism systems. In Achromobacter sp. MPS 12, degradation of MP was catalyzed by C-P lyase incapable of degrading GP (C-P lyase I). Adaptation to growth on GP yielded the strain Achromobacter sp. MPS 12A, which retained its ability to degrade MP via C-P lyase I and was capable of degrading GP with formation of sarcosine, thus suggesting the involvement of a GP-specific C-P lyase II. O. anthropi GPK 3 also degraded MP via C-P lyase I, but degradation of GP in it was initiated by glyphosate oxidoreductase, which was followed by product transformation via the phosphonatase pathway.

  15. Interaction of diethyl aniline methylphosphonate with DNA: Spectroscopic and isothermal titration calorimetry

    Lu Yan, E-mail: [College of Chemistry and Environmental Science, Henan Normal University, Xinxiang, Henan 453007 (China); Xu Meihua; Wang Gongke; Zheng Yun [College of Chemistry and Environmental Science, Henan Normal University, Xinxiang, Henan 453007 (China)


    In this study the diethyl aniline methylphosphonate (DAM) was synthesized, the interaction of DAM with ct-DNA has been investigated by fluorescence spectra, UV spectra, molecular modeling and isothermal titration calorimetry (ITC). The binding constant of DAM to ct-DNA calculated from both isothermal titration calorimetry and fluorescence spectra were found to be in the 10{sup 4} M{sup -1} range. According to the ethidium bromide displacement studies, UV spectra and isothermal titration calorimetry experimental results, it can be concluded that DAM is an intercalator that can slide into the G-C rich region of ct-DNA. Furthermore, the results obtained from molecular modeling corroborated the experimental results obtanied from spectroscopic and ITC investigations. At the same time, fluorescence spectra suggested that the mechanism of the interaction of DAM to ct-DNA was a static enhancing type. ITC data showed that ct-DNA/DAM binding is enthalpy controlled. - Research highlights: The interaction of DAM with ct-DNA is a static enhancing type. DAM can slide into the G-C rich region of ct-DNA. The binding of DAM to ct-DNA is enthalpy controlled. The hydrogen bonding forces play an essential role in the binding process.

  16. Destruction of methylphosphonic acid in a supercritical water oxidation bench-scale double wall reactor

    Bambang Veriansyah; Eun-Seok Song; Jae-Duck Kim


    The destruction of methylphosphonic acid (MPA), a final product by hydrolysis/neutralization of organophosphorus agents such as satin and VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothionate), was investigated in a a bench-scale, continuous concentric vertical double wall reactor under supercritical water oxidation condition. The experiments were conducted at a temperature range of 450-600~C and a fixed pressure of 25 MPa. Hydrogen peroxide was used as an oxidant. The destruction efficiency (DE) was monitored by analyzing total organic carbon (TOC) and MPA concentrations using ion chromatography on the liquid effluent samples. The results showed that the DE of MPA up to 99.999% was achieved at a reaction temperature of 600~C, oxygen concentration of 113% storichiometric requirement, and reactor residence time of 8 sec. On the basis of the data derived from experiments, a global kinetic rate equation for the DE of MPA and DE of TOC were developed by nonlinear regression analysis. The model predictions agreed well with the experimental data.

  17. Metatranscriptomic and functional metagenomic analysis of methylphosphonate utilization by marine bacteria

    Asuncion eMartinez


    Full Text Available Aerobic degradation of methylphosphonate (MPn by marine bacterioplankton has been hypothesized to contribute significantly to the ocean’s methane supersaturation, yet little is known about MPn utilization by marine microbes. To identify the microbial taxa and metabolic functions associated with MPn-driven methane production we performed parallel metagenomic, metatranscriptomic, and functional screening of microcosm perturbation experiments using surface water collected in North Pacific Subtropical Gyre. In nutrient amended microcosms containing MPn, a substrate-driven microbial succession occurred. Initially, the addition of glucose and nitrate resulted in a bloom of Vibrionales and a transcriptional profile dominated by glucose-specific PTS transport and polyhydroxyalkanoate biosynthesis. Transcripts associated with phosphorus (P acquisition were also overrepresented and suggested that the addition of glucose and nitrate had driven the community to P depletion. At this point, a second community shift occurred characterized by the increase in C-P lyase containing microbes of the Vibrionales and Rhodobacterales orders. Transcripts associated with C-P lyase components were among the most highly expressed at the community level, and only C-P lyase clusters were recovered in a functional screen for MPn utilization, consistent with this pathway being responsible for the majority, if not all the methane accumulation we observed. Our results identify specific bacterioplankton taxa that can utilize MPn aerobically under conditions of P limitation using the C-P lyase pathway, and thereby elicit a significant increase in the dissolved methane concentration.

  18. Energetics and Dynamics of the Reactions of O(3P) with Dimethyl Methylphosphonate and Sarin

    Conforti, Patrick F.; Braunstein, Matthew; Dodd, James A.


    Electronic structure and molecular dynamics calculations were performed on the reaction systems O(3P) + sarin and O(3P) + dimethyl methylphosphonate (DMMP), a sarin simulant. Transition state geometries, energies, and heats of reaction for the major reaction pathways were determined at several levels of theory, including AM1, B3LYP/6-311+G(d,p), and CBS-QB3. The major reaction pathways for both systems are similar and include H-atom abstraction, H-atom elimination, and methyl elimination, in rough order from low to high energy. The H-atom abstraction channels have fairly low barriers (˜10 kcal mol-1) and are close to thermoneutral, while the other channels have relatively high energy barriers (>40 kcal mol-1) and a wide range of reaction enthalpies. We have also found a two-step pathway leading to methyl elimination through O-atom attack on the phosphorus atom for DMMP and sarin. For sarin, the two-step methyl elimination pathway is significantly lower in energy than the single-step pathway. We also present results of O(3P) + sarin and O(3P) + DMMP reaction cross sections over a broad range of collision energies (2-10 km s-1 collision velocities) obtained using the direct dynamics method with an AM1 semiempirical potential. These excitation functions are intended as an approximate guide to future hyperthermal measurements, which to our knowledge have not yet examined either of these systems. The reaction barriers, reaction enthalpies, transition state structures, and excitation functions are generally similar for DMMP and sarin, with some moderate differences for methyl elimination energetics, which indicates DMMP will likely be a good substitute for sarin in many O(3P) chemical investigations.

  19. Nucleoside-O-Methyl-(H)-Phosphinates: Novel Monomers for the Synthesis of Methylphosphonate Oligonucleotides Using H-Phosphonate Chemistry.

    Kostov, Ondřej; Páv, Ondřej; Rosenberg, Ivan


    This unit comprises the straightforward synthesis of protected 2'-deoxyribonucleoside-O-methyl-(H)-phosphinates in both 3'- and 5'-series. These compounds represent a new class of monomers compatible with the solid-phase synthesis of oligonucleotides using H-phosphonate chemistry and are suitable for the preparation of both 3'- and 5'-O-methylphosphonate oligonucleotides. The synthesis of 4-toluenesulfonyloxymethyl-(H)-phosphinic acid as a new reagent for the preparation of O-methyl-(H)-phosphinic acid derivatives is described. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  20. Reactions of Cre with methylphosphonate DNA: similarities and contrasts with Flp and vaccinia topoisomerase.

    Chien-Hui Ma

    Full Text Available BACKGROUND: Reactions of vaccinia topoisomerase and the tyrosine site-specific recombinase Flp with methylphosphonate (MeP substituted DNA substrates, have provided important insights into the electrostatic features of the strand cleavage and strand joining steps catalyzed by them. A conserved arginine residue in the catalytic pentad, Arg-223 in topoisomerase and Arg-308 in Flp, is not essential for stabilizing the MeP transition state. Topoisomerase or its R223A variant promotes cleavage of the MeP bond by the active site nucleophile Tyr-274, followed by the rapid hydrolysis of the MeP-tyrosyl intermediate. Flp(R308A, but not wild type Flp, mediates direct hydrolysis of the activated MeP bond. These findings are consistent with a potential role for phosphate electrostatics and active site electrostatics in protecting DNA relaxation and site-specific recombination, respectively, against abortive hydrolysis. METHODOLOGY/PRINCIPAL FINDINGS: We have examined the effects of DNA containing MeP substitution in the Flp related Cre recombination system. Neutralizing the negative charge at the scissile position does not render the tyrosyl intermediate formed by Cre susceptible to rapid hydrolysis. Furthermore, combining the active site R292A mutation in Cre (equivalent to the R223A and R308A mutations in topoisomerase and Flp, respectively with MeP substitution does not lead to direct hydrolysis of the scissile MeP bond in DNA. Whereas Cre follows the topoisomerase paradigm during the strand cleavage step, it follows the Flp paradigm during the strand joining step. CONCLUSIONS/SIGNIFICANCE: Collectively, the Cre, Flp and topoisomerase results highlight the contribution of conserved electrostatic complementarity between substrate and active site towards transition state stabilization during site-specific recombination and DNA relaxation. They have potential implications for how transesterification reactions in nucleic acids are protected against

  1. Adsorption and decomposition of dimethyl methylphosphonate on pristine and mono-vacancy defected graphene: A first principles study

    Majumder, Chiranjib


    Here we report the adsorption and decomposition behavior of dimethyl methyl-phosphonate (DMMP) on pristine and defected graphene using the first principles theory. The primary objective of this study is to highlight the importance of a vacancy defect on the adsorption mechanism of a molecule. In order to account for the weak forces involved between the molecule and graphene, we have used dispersion corrected total energy calculations along with generalized gradient approximation scheme for the exchange correlation energy. Among various possible configurations, the most stable geometry shows oxygen atom of the DMMP molecule favors to be close to the surface plane and bind with one of the unsaturated carbon atoms at the defect site. The molecule-substrate interaction energy is stronger for defected graphene than pristine graphene. The decomposition of the DMMP molecule at the vacancy site of the defected graphene has been investigated. For the dissociative adsorption, it is seen that the Csbnd H bond of the DMMP breaks and H atom is transferred to one of the low-coordinated C-atoms at the vicinity of the defect, forming new Csbnd H bond. In addition, the Csbnd C bond formation between graphene and DMMP occurs. Finally, the nature of bonding and electronic structure at the interface was interpreted through site projected electronic density of states analysis.

  2. Study of a QCM Dimethyl Methylphosphonate Sensor Based on a ZnO-Modified Nanowire-Structured Manganese Dioxide Film

    Guang Li


    Full Text Available Sensitive, selective and fast detection of chemical warfare agents is necessary for anti-terrorism purposes. In our search for functional materials sensitive to dimethyl methylphosphonate (DMMP, a simulant of sarin and other toxic organophosphorus compounds, we found that zinc oxide (ZnO modification potentially enhances the absorption of DMMP on a manganese dioxide (MnO2 surface. The adsorption behavior of DMMP was evaluated through the detection of tiny organophosphonate compounds with quartz crystal microbalance (QCM sensors coated with ZnO-modified MnO2 nanofibers and pure MnO2 nanofibers. Experimental results indicated that the QCM sensor coated with ZnO-modified nanostructured MnO2 film exhibited much higher sensitivity and better selectivity in comparison with the one coated with pure MnO2 nanofiber film. Therefore, the DMMP sensor developed with this composite nanostructured material should possess excellent selectivity and reasonable sensitivity towards the tiny gaseous DMMP species.

  3. Biological evaluation of {sup 153}Sm and {sup 166}Ho complexes with tetraazamacrocycles containing methylcarboxylate and/or methylphosphonate pendant arms

    Marques, F.; Gano, L.; Campello, M.P.; Lacerda, S.; Santos, I. [Inst. Tecnologico e Nuclear, Sacavem (Portugal)


    {sup 153}Sm and {sup 166}Ho complexes with two series of tetraazamacrocyclic ligands containing methylcarboxylate and/or methylphosphonate pendant arms were synthesized and their charge, lipophilicity, protein binding and in vitro and in vivo behaviour evaluated. The first series has the same backbone, a 14-membered tetraazamacrocycle containing a pyridine unit with different pendant arms, namely methylcarboxylates (ac{sub 3}py14) or methylphosphonates (MeP{sub 2}py14 and P{sub 3}py14). The second series comprises 12- to 14-membered tetraazamacrocycles having methylcarboxylates and/or methylphosphonates as pendant arms (trans-DO2A2P, TRITA, TRITP, TETA and TETP). The {sup 153}Sm/{sup 166}Ho complexes with the 14-membered tetraazamacrocycles containing the pyridine unit are neutral, hydrophilic, have a significant plasmatic protein binding, are unstable in vivo and present a slow rate of radioactivity excretion and high hepatic retention. {sup 153}Sm/{sup 166}Ho complexes with the 12- to 14-membered tetraazamacrocycles are quantitatively prepared, except those with TETP. These complexes are hydrophilic, have an overall negative charge and present a medium to low plasmatic protein binding. The {sup 153}Sm/{sup 166}Ho-trans-DO2A2P, {sup 153}Sm/{sup 166}Ho-TRITA and {sup 166}Ho-TRITP complexes are stable in vitro and in vivo, presenting a rapid clearance from main organs and a high rate of whole body radioactivity excretion. Biological profile of {sup 153}Sm/{sup 166}Ho-TRITA complexes makes them promising candidates for therapy when conjugated to a biomolecule, while {sup 166}Ho-TRITP is potentially useful for bone targeting due to its considerable uptake by bone. (orig.)

  4. Comparison of Cluster, Slab, and Analytic Potential Models for the Dimethyl Methylphosphonate (DMMP)/TiO2 (110) Intermolecular Interaction

    Yang, Li; Tunega, Daniel; Xu, Lai; Govind, Niranjan; Sun, Rui; Taylor, Ramona; Lischka, Hans; De Jong, Wibe A.; Hase, William L.


    In a previous study (J. Phys. Chem. C 2011, 115, 12403) cluster models for the TiO2 rutile (110) surface and MP2 calculations were used to develop an analytic potential energy function for dimethyl methylphosphonate (DMMP) interacting with this surface. In the work presented here, this analytic potential and MP2 cluster models are compared with DFT "slab" calculations for DMMP interacting with the TiO2 (110) surface and with DFT cluster models for the TiO2 (110) surface. The DFT slab calculations were performed with the PW91 and PBE functionals. The analytic potential gives DMMP/ TiO2 (110) potential energy curves in excellent agreement with those obtained from the slab calculations. The cluster models for the TiO2 (110) surface, used for the MP2 calculations, were extended to DFT calculations with the B3LYP, PW91, and PBE functional. These DFT calculations do not give DMMP/TiO2 (110) interaction energies which agree with those from the DFT slab calculations. Analyses of the wave functions for these cluster models show that they do not accurately represent the HOMO and LUMO for the surface, which should be 2p and 3d orbitals, respectively, and the models also do not give an accurate band gap. The MP2 cluster models do not accurately represent the LUMO and that they give accurate DMMP/TiO2 (110) interaction energies is apparently fortuitous, arising from their highly inaccurate band gaps. Accurate cluster models, consisting of 7, 10, and 15 Ti-atoms and which have the correct HOMO and LUMO properties, are proposed. The work presented here illustrates the care that must be taken in "constructing" cluster models which accurately model surfaces.

  5. Computational Study of the Adsorption of Dimethyl Methylphosphonate (DMMP) on the (0 1 0) Surface of Anatase TiO2 With and Without Faceting


    Computational study of the adsorption of dimethyl methylphosphonate (DMMP) on the (0 1 0) surface of anatase TiO2 with and without faceting V.M...DMMP) on the (0 1 0) surface of anatase TiO2, which is isostructural with the (1 0 0), has been studied using density functional theory and two...also close to those found elsewhere for the rutile (1 1 0) and anatase (1 0 1) surfaces. A possible first step in the dissociative adsorption of DMMP

  6. Method for the analysis of the methylphosphonic acid metabolites of sarin and its ethanol-substituted analogue in urine as applied to the victims of the Tokyo sarin disaster.

    Minami, M; Hui, D M; Katsumata, M; Inagaki, H; Boulet, C A


    An analysis method for the methylphosphonic acid metabolites of sarin in urine using trimethylsilyl derivatization and flame photometric detection is described in this report. Authentic reference standards of isopropyl methylphosphonic acid (IMPA) and ethyl methylphosphonic acid (EMPA) as well as methylphosphonic acid were employed to estimate the concentration in human urine. A sample pretreatment procedure was developed for urine using a column of cation-loaded ion-exchange resins (Ag+ -, Ba2+ - or H+ -Dowex) and adjusting the pH of the eluate from the column to 3.75-3.85 improved recovery of the target compounds. The eluate was evaporated to dryness under vacuum prior to trimethylsilylation, to remove water and any hydroxy- or amino-carrying volatile substances. The sarin metabolites, because of their low volatility, were concentrated and could be derivatized for analysis. The use of synthesized authentic sarin and ethylsarin metabolites, i.e., IMPA and EMPA, made it possible to establish the necessary sample pretreatment procedures for derivatization and gas chromatography-flame photometric detection (GC-FPD) analysis. The detection limits were 0.025 ppm both for EMPA and [MPA, and 0.625 microM for MPA, respectively. This method can be useful for estimating the exposure level to sarin by assaying the metabolites in urine and it is applicable to a large numbers of samples.

  7. Effect of dosage of expandable graphite, dimethyl methylphosphonate, triethanolamine, and isocyanate on fluidity, mechanical, and flame retardant properties of polyurethane materials in coal reinforcement

    Hu Xiangming; Wang Deming; Cheng Weimin


    In this study, orthogonal experiments were conducted to investigate the influence of expandable graphite (EG), dimethyl methylphosphonate (DMMP), triethanolamine (TEA), and isocyanate content on the com-pressive and bonding strengths, oxygen index, and fluidity of rigid polyurethane foam (RPUF). The results revealed that EG significantly increased the oxygen index of RPUF, enlarged the diameter of foam cells, and decreased the cell-closed content in foam;thus, leading to a pressure drop in RPUF. However, exces-sive EG was capable of reducing the fluidity of polyurethane slurry. TEA exhibited significant influence on the compressive strength of RPUF, which dropped initially, and then increased. DMMP had a remarkable effect on the flame retardant property and compressive strength of RPUF. Compressive strength of RPUF initially displayed an increase followed by a decrease with increasing dosage of DMMP, and achieved the maximum value at DMMP dosage of 4%. DMMP could effectively reduce the diameter of RPUF cells lead-ing to an increase in the percentage of close area in foam. DMMP displayed the flame-retardation effects mainly in the gas phase leading to a significant enhancement in the oxygen index of RPUF. Moreover, the compressive strength and bonding strength of RPUF decrease significantly with the increase of isocyanate content due to the increased blowing efficiency by the CO2. The oxygen index and flowing length of foam increased with the increase in isocyanate dosage.

  8. Acute effects of a sarin-like organophosphorus agent, bis(isopropyl methyl)phosphonate, on cardiovascular parameters in anaesthetized, artificially ventilated rats

    Watanabe, Yoshimasa [Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Itoh, Takeo, E-mail: [Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Shiraishi, Hiroaki [Department of Forensic Medicine, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Maeno, Yoshitaka [Department of Forensic Medical Science, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Arima, Yosuke; Torikoshi, Aiko; Namera, Akira [Department of Forensic Medicine, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Makita, Ryosuke [Department of Nursing, Faculty of Health Sciences, Hiroshima Cosmopolitan University, Hiroshima (Japan); Yoshizumi, Masao [Department of Cardiovascular Physiology and Medicine, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Nagao, Masataka [Department of Forensic Medicine, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan)


    The organophosphorus compound sarin irreversibly inhibits acetylcholinesterase. We examined the acute cardiovascular effects of a sarin-like organophosphorus agent, bis(isopropyl methyl)phosphonate (BIMP), in anaesthetized, artificially ventilated rats. Intravenous administration of BIMP (0.8 mg/kg; the LD50 value) induced a long-lasting increase in blood pressure and tended to increase heart rate. In rats pretreated with the non-selective muscarinic-receptor antagonist atropine, BIMP significantly increased both heart rate and blood pressure. In atropine-treated rats, hexamethonium (antagonist of ganglionic nicotinic receptors) greatly attenuated the BIMP-induced increase in blood pressure without changing the BIMP-induced increase in heart rate. In rats treated with atropine plus hexamethonium, intravenous phentolamine (non-selective α-adrenergic receptor antagonist) plus propranolol (non-selective β-adrenergic receptor antagonist) completely blocked the BIMP-induced increases in blood pressure and heart rate. In atropine-treated rats, the reversible acetylcholinesterase inhibitor neostigmine (1 mg/kg) induced a transient increase in blood pressure, but had no effect on heart rate. These results suggest that in anaesthetized rats, BIMP induces powerful stimulation of sympathetic as well as parasympathetic nerves and thereby modulates heart rate and blood pressure. They may also indicate that an action independent of acetylcholinesterase inhibition contributes to the acute cardiovascular responses induced by BIMP. - Highlights: • A sarin-like agent BIMP markedly increased blood pressure in anaesthetized rats. • Muscarinic receptor blockade enhanced the BIMP-induced increase in blood pressure. • Ganglionic nicotinic receptor blockade attenuated the BIMP-induced response. • Blockade of α- as well as β-receptors attenuated the BIMP-induced response.

  9. Simultaneous quantification of soman and VX adducts to butyrylcholinesterase, their aged methylphosphonic acid adduct and butyrylcholinesterase in plasma using an off-column procainamide-gel separation method combined with UHPLC-MS/MS.

    Liu, Chang-Cai; Huang, Gui-Lan; Xi, Hai-Ling; Liu, Shi-Lei; Liu, Jing-Quan; Yu, Hui-Lan; Zhou, Shi-Kun; Liang, Long-Hui; Yuan, Ling


    This work describes a novel and sensitive non-isotope dilution method for simultaneous quantification of organophosphorus nerve agents (OPNAs) soman (GD) and VX adducts to butyrylcholinesterase (BChE), their aged methylphosphonic acid (MeP) adduct and unadducted BChE in plasma exposed to OPNA. OPNA-BChE adducts were isolated with an off-column procainamide-gel separation (PGS) from plasma, and then digested with pepsin into specific adducted FGES(*)AGAAS nonapeptide (NP) biomarkers. The resulting NPs were detected by UHPLC-MS/MS MRM. The off-column PGS method can capture over 90% of BChE, MeP-BChE, VX-BChE and GD-BChE from their respective plasma materials. One newly designed and easily synthesized phosphorylated BChE nonapeptide with one Gly-to-Ala mutation was successfully reported to serve as internal standard instead of traditional isotopically labeled BChE nonapeptide. The linear range of calibration curves were from 1.00-200ngmL(-1) for VX-NP, 2.00-200ngmL(-1) for GD-NP and MeP-NP (R(2)≥0.995), and 3.00-200ngmL(-1) for BChE NP (R(2)≥0.990). The inter-day precision had relative standard deviation (%RSD) of VX-NP, GD-NP, MeP-NP and BChE NP, respectively. OPNA-exposed quality control plasma samples were characterized as part of method validation. Investigation of plasma samples unexposed to OPNA revealed no baseline values or interferences. Using the off-column PGS method combined with UHPLC-MS/MS, VX-NP and GD-NP adducts can be unambiguously detected with high confidence in 0.10ngmL(-1) and 0.50ngmL(-1) of exposed human plasma respectively, only requiring 0.1mL of plasma sample and taking about four hours without special sample preparation equipment. These improvements make it a simple, sensitive and robust PGS-UHPLC-MS/MS method, and this method will become an attractive alternative to immunomagnetic separation (IMS) method and a useful diagnostic tool for retrospective detection of OPNA exposure with high confidence. Furthermore, using the developed

  10. Drinking Water Criteria for the Groundwater Pollutant Diisopropyl Methylphosphonate (DIMP).


    moderate corneal opacity lasting seven days, some conjunctival irritation, but no iritis . The aqueous suspension of DIMP produced no acute irritation...irritation studies conducted by the method of Draize show that technical grade DIMP produces moderate corneal opacity lasting seven days. No iritis was

  11. Nerve agent analogues that produce authentic soman, sarin, tabun, and cyclohexyl methylphosphonate-modified human butyrylcholinesterase.

    Gilley, Cynthia; MacDonald, Mary; Nachon, Florian; Schopfer, Lawrence M; Zhang, Jun; Cashman, John R; Lockridge, Oksana


    The goal was to test 14 nerve agent model compounds of soman, sarin, tabun, and cyclohexyl methylphosphonofluoridate (GF) for their suitability as substitutes for true nerve agents. We wanted to know whether the model compounds would form the identical covalent adduct with human butyrylcholinesterase that is produced by reaction with true nerve agents. Nerve agent model compounds containing thiocholine or thiomethyl in place of fluorine or cyanide were synthesized as Sp and Rp stereoisomers. Purified human butyrylcholinesterase was treated with a 45-fold molar excess of nerve agent analogue at pH 7.4 for 17 h at 21 degrees C. The protein was denatured by boiling and was digested with trypsin. Aged and nonaged active site peptide adducts were quantified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry of the tryptic digest mixture. The active site peptides were isolated by HPLC and analyzed by MALDI-TOF-TOF mass spectrometry. Serine 198 of butyrylcholinesterase was covalently modified by all 14 compounds. Thiocholine was the leaving group in all compounds that had thiocholine in place of fluorine or cyanide. Thiomethyl was the leaving group in the GF thiomethyl compounds. However, sarin thiomethyl compounds released either thiomethyl or isopropyl, while soman thiomethyl compounds released either thiomethyl or pinacolyl. Thiocholine compounds reacted more rapidly with butyrylcholinesterase than thiomethyl compounds. Labeling with the model compounds resulted in aged adducts that had lost the O-alkyl group (O-ethyl for tabun, O-cyclohexyl for GF, isopropyl for sarin, and pinacolyl for soman) in addition to the thiocholine or thiomethyl group. The nerve agent model compounds containing thiocholine and the GF thiomethyl analogue were found to be suitable substitutes for true soman, sarin, tabun, and GF in terms of the adduct that they produced with human butyrylcholinesterase. However, the soman and sarin thiomethyl compounds yielded two types of adducts, one of which was thiomethyl phosphonate, a modification not found after treatment with authentic soman and sarin.

  12. Sorption Efficiency of a New Sorbent towards Cadmium(II: Methylphosphonic Acid Grafted Polystyrene Resin

    Nacer Ferrah


    Full Text Available A new chelating polymeric sorbent has been developed using polystyrene resin grafted with phosphonic acid. After characterization by FTIR and elementary analysis, the new resin has been investigated in liquid-solid extraction of cadmium(II. The results indicated that phosphonic resin could adsorb Cd(II ion effectively from aqueous solution. The adsorption was strongly dependent on the pH of the medium and the optimum pH value level for better sorption was between 3.2 and 5.2. The influence of other analytical parameters including contact time, amount of resin, metal ion concentration, and the presence of some electrolytes was investigated. The maximum uptake capacity of Cd(II ions was 37,9 mg·g−1 grafted resin at ambient temperature, at an initial pH value of 5.0. The overall adsorption process was best described by pseudo second-order kinetic. When Freundlich and Langmuir isotherms were tested, the latter had a better fit with the experimental data. Furthermore, more than 92% of Cd(II could be eluted by using 1.0 mol·L−1 HCl in one cycle.

  13. [Catabolism of methylphosphonic acid and its physiological regulation in Escherichia coli].

    Matys, S V; Laurinavichius, K S; Nesmeianova, M A


    It was found that methyl phosphonic acid (Pn) was degraded by different Escherichia coli strains, which utilized it as the sole phosphorus source with resulting methane formation. This ability was influenced by mutations in the regulatory genes of the pho regulon. Thus, Pn was not degraded by an E. coli mutant defective in the regulatory phoB gene, responsible for the induction of pho-regulon proteins during phosphorus starvation. The intensity of Pn degradation depended on the age and concentration of the inoculum. Preincubation of bacteria in the presence of Pn accelerated subsequent degradation of both methyl phosphonic acid and its esters. Cultures developing from a small amount of inoculum degraded Pn more efficiently than heavily inoculated cultures that underwent only one cell division. However, cultures heavily inoculated with adapted cells degraded Pn as efficiently as cultures developing from a small amount of inoculum. Aeration was an important factor regulating Pn degradation: Pn was degraded more efficiently under anaerobic conditions regardless of the amount of inoculum.

  14. Toxicology Study of Diisopropyl Methylphosphonate and Dicyclopentadiene in Mallard Ducks, Bobwhite Quail and Mink.


    15.6*C. Eggs were set once a week in a Jamesway , single stage, 252 incubator. 3 The eggs were incubated for 23 days at an average temperature of 37.5*C... Jamesway stage Model 252 incubator. 3 The incubator was maintained at an average internal temperature of 37.5’C (range 36.9 to 38.1 0 C) and average...into pedigree hatching baskets and were transferred to a hatching unit ( Jamesway Model 252) on day 21. The average temperature and relative humidity

  15. Methyl-phospho-nic acid, CH3PO(OH)2.

    Reuter, Hans; Reichelt, Martin


    The asymmetric unit of the title compound, CH5O3P, contains two independent mol-ecules with nearly identical bond lengths and angles. In the crystal, each of the mol-ecules acts as acceptor (P=O) and donor (P-OH) of four hydrogen bonds to three adjacent mol-ecules, resulting in the formation of two different bilayers (one for each mol-ecule) stacked perpendicular to the a axis in the crystal.

  16. Quartz Crystal Microbalance Studies Of Dimethyl Methylphosphonate Sorption Into Trisilanolphenyl-Poss Films


    VX. GB and GD dissolve in water and, at pH values PO OH F P O F O C H H H P O F O C H H H + Sarin (GB) Methylphosphono- fluoridic acid Propylene 5...quantitatively determined the amount of DMMP adsorbed onto an alumina-supported iron and cerium oxide surface using FTIR.18,19 At 25 °C, the alumina...LB-film. This value is actually larger than the degradation capacity of alumina-supported iron and cerium oxide surfaces, reported to be 510 µmol of

  17. Evaluation of Dimethyl Methylphosphonate and Exo-Tetrahydrodi- (Cyclopentadiene) in a Battery of in Vitro Short-Term Assays


    sites of both chromatids of a chromosome . These include breaks, fragments, markers (i.e., dicentrics , rings), and gaps. 2. Chromatid aberrations - changes...Ames Salmonella/mammalian microsomal mutagenicity assay, the CHO/HGPRT gene mutation assay, the CHO/sister chromatid exchange assay, the CHO/ chromosome ...exhibited a low clastogenic activity in the CHO/ chromosome aberrations assay and was negative in the remaining four assays. Compound JP-1O also had a

  18. First-Principles Study of Adsorption of Dimethyl Methylphosphonate on the TiO2 Anatase (001) Surface: Formation of a Stable Titanyl (Ti=O) Site


    Anatase (001) Surface: Formation of a Stable Titanyl (TidO) Site V. M. Bermudez Electronics Science and Technology Division, Naval Research at a 5-fold-coordinated Ti5c site. Figure 1 shows a model 25 for the corresponding structure on anatase (101) and also identifies the T5c, Ti6c...the UHV experimental data, computational results for DMMP on OH-free rutile (110) and anatase (101) and (100) surfaces24,25 find that dissociation is

  19. Computational Study of the Adsorption of Dimethyl Methylphosphonate (DMMP) on the (010) Surface of Anatase TiO2 With and Without Faceting


    unfa- ceted surface via a Ti5c---O bond to a methoxy O atom. At the RHF level used in geometry opti- mization the resulting structure was less stable...of the unfa- ceted anatase (010) surfacea atomb this workc ref. 37d ref. 22e Ti5c 0.02; -0.15 0.04; -0.14 0.02; -0.16 O|| 0.02; +0.18 0.04; +0.18

  20. Effect of Humidity on the Interaction of Dimethyl Methylphosphonate (DMMP) Vapor with SiO2 and Al2O3 Surfaces, Studied Using Infrared Attenuated Total Reflection Spectroscopy


    prism faces. Spectrawere recordedusingaFourier transform infrared ( FTIR ) spectrometer with a “narrow-band” HgxCd1-xTe (MCT-A) detec- tor. No polarizer...was used, and the intrinsic polarization of the beam produced by an FTIR spectrometer is typically fairly weak.56 Usually 2000 scans were averaged at...scattering.49 2.3. Sample Preparation and Characterization. Follow- ing previous3-5 work, the a-SiO2/Si samples were grown using ultraviolet/ ozone (UV/O3

  1. Application of Solid Phase Microextraction with Gas Chromatography-Mass Spectrometry as a Rapid, Reliable, and Safe Method for Field Sampling and Analysis of Chemical Warfare Agent Precursors


    nations, including plating solutions, metallurgical processes such as silver and gold refining, and as an intermediate in the manufacture of resin...used in numerous processes in industrial nations, including plating and other metallurgical processes such as silver and gold refining, and as an...malononitrile, diisopropyl methylphosphonate (DIMP), diethyl methylphosphonate (DEMP), malathion, potassium cyanide , and O,O’diethyl methyl

  2. Synthesis, fluorescence properties and the promising cytotoxicity of pyrene–derived aminophosphonates

    Rodriguez Moya, Maria; Wrona-Piotrowicz, Anna; Gajek, Gabriela


    Summary A large series of variously substituted amino(pyren-1-yl)methylphosphonic acid derivatives was synthesized using a modified aza-Pudovik reaction in 20–97% yields. The fluorescence properties of the obtained compounds were investigated revealing that N-alkylamino(pyren-1-yl)methylphosphonic derivatives are stronger emissive compounds than the corresponding N-aryl derivatives. N-Benzylamino(pyren-1-yl)methylphosphonic acid displayed strong fluorescence (ΦF = 0.68) in phosphate-buffered saline (PBS). The influence of a series of derivatives on two colon cancer cell lines HT29 and HCT116 was also investigated. The most promising results were obtained for N-(4-methoxyphenyl)amino(pyren-1-yl)methylphosphonate, which was found to be cytotoxic for the HCT116 cancer cell line (IC50 = 20.8 μM), simultaneously showing weak toxicity towards normal lymphocytes (IC50 = 230.8 µM). PMID:27559373

  3. Derivatization of organophosphorus nerve agent degradation products for gas chromatography with ICPMS and TOF-MS detection.

    Richardson, Douglas D; Caruso, Joseph A


    Separation and detection of seven V-type (venomous) and G-type (German) organophosphorus nerve agent degradation products by gas chromatography with inductively coupled plasma mass spectrometry (GC-ICPMS) is described. The nonvolatile alkyl phosphonic acid degradation products of interest included ethyl methylphosphonic acid (EMPA, VX acid), isopropyl methylphosphonic acid (IMPA, GB acid), ethyl hydrogen dimethylamidophosphate sodium salt (EDPA, GA acid), isobutyl hydrogen methylphosphonate (IBMPA, RVX acid), as well as pinacolyl methylphosphonic acid (PMPA), methylphosphonic acid (MPA), and cyclohexyl methylphosphonic acid (CMPA, GF acid). N-(tert-Butyldimethylsilyl)-N-methyltrifluroacetamide with 1% TBDMSCl was utilized to form the volatile TBDMS derivatives of the nerve agent degradation products for separation by GC. Exact mass confirmation of the formation of six of the TBDMS derivatives was obtained by GC-time of flight mass spectrometry (TOF-MS). The method developed here allowed for the separation and detection of all seven TBDMS derivatives as well as phosphate in less than ten minutes. Detection limits for the developed method were less than 5 pg with retention times and peak area precisions of less than 0.01 and 6%, respectively. This method was successfully applied to river water and soil matrices. To date this is the first work describing the analysis of chemical warfare agent (CWA) degradation products by GC-ICPMS.

  4. Determination of nerve agent metabolites in human urine by isotope-dilution gas chromatography-tandem mass spectrometry after solid phase supported derivatization.

    Lin, Ying; Chen, Jia; Yan, Long; Guo, Lei; Wu, Bidong; Li, Chunzheng; Feng, Jianlin; Liu, Qin; Xie, Jianwei


    A simple and sensitive method has been developed and validated for determining ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), isobutyl methylphosphonic acid (iBuMPA), and pinacolyl methylphosphonic acid (PMPA) in human urine using gas chromatography-tandem mass spectrometry (GC-MS/MS) coupled with solid phase derivatization (SPD). These four alkyl methylphosphonic acids (AMPAs) are specific hydrolysis products and biomarkers of exposure to classic organophosphorus (OP) nerve agents VX, sarin, RVX, and soman. The AMPAs in urine samples were directly derivatized with pentafluorobenzyl bromide on a solid support and then extracted by liquid-liquid extraction. The analytes were quantified with isotope-dilution by negative chemical ionization (NCI) GC-MS/MS in a selected reaction monitoring (SRM) mode. This method is highly sensitive, with the limits of detection of 0.02 ng/mL for each compound in a 0.2 mL sample of human urine, and an excellent linearity from 0.1 to 50 ng/mL. It is proven to be very suitable for the qualitative and quantitative analyses of degradation markers of OP nerve agents in biomedical samples.

  5. Evaporation and Degradation of a Sessile Droplet of VX on an Impermeable Surface


    methylphosphonic acid and VX-pyro) and hydrophobic (VX-disulfide) components occurs. The hydrophilic components make up the core of the droplet and the...hydrophobic component comprises the shell. Continuum models of the process suggest that experimental observations cannot be reproduced without accounting...1 2. METHODS AND MATERIALS .............................................................................5 2.1

  6. Design and Construction of a High Vacuum Surface Analysis Instrument to Study Chemistry at Nanoparticulate Surfaces


    XPS Aerogel Prepared Conventionally Prepared Chemical Weapon Chemical Warfare Agent Diisopropyl Fluorophosphate Diisopropyl Methylphosphonate...have shown promise as effective decontamination reactants that do not possess the shortcomings of solution- based strategies. In particular, gold ...have also been investigated.16 Recent studies have demonstrated catalytic degradation of DMMP by titania-supported gold nanoparticles.17 9

  7. Disruption of a binary organogel by the chemical warfare agent soman (GD) and common organophosphorus simulants

    Hiscock, Jennifer R.; Sambrook, Mark R; Ede, Jayne A.; Wells, Neil J.; Philip A. Gale


    The chemical warfare agent (CWA) soman (GD) acts as a molecular stimulus for the disruption of an anthracene-based binary organogel prepared in cyclohexane. The CWA simulants dimethyl methylphosphonate (DMMP) and diethyl chlorophosphate (DCP) were also found to disrupt the binary organogel through changes in solvent polarity and reactions with the gelator.\\ud \\ud

  8. Decontamination Strategy for Large Area and/or Equipment Contaminated with Chemical and Biological Agents using a High Energy Arc Lamp (HEAL)


    Methylphosphonate Vapor at TiO2 Surfaces, J. Phys. Chem. B 109 (2005) 19779-19785. [10] M.A. Fox, M.T. Dulay, Heterogenous Photocatalysis , Chem. Rev...93 (1993) 341-357. [11] M.R. Hoffman, et al, Environmental Applications of Semiconductor Photocatalysis , Chem. Rev. 95 (1995) 69-96. [12] J.B

  9. Towards decomposition of live chemical agents by pyrotechnic mixtures

    Bouma, R.H.B.; Noort, D.


    The aim of this study is to contribute to improved EOD neutralisation techniques against improvised explosive devices (IEDs) containing chemical agents. The decomposition of dimethyl methylphosphonate (DMMP) when exposed to a burning aluminum/potassium nitrate pyrotechnic mixture is studied experime

  10. Towards decomposition of live chemical agents by pyrotechnic mixtures

    Bouma, R.H.B.; Noort, D.


    The aim of this study is to contribute to improved EOD neutralisation techniques against improvised explosive devices (IEDs) containing chemical agents. The decomposition of dimethyl methylphosphonate (DMMP) when exposed to a burning aluminum/potassium nitrate pyrotechnic mixture is studied experime

  11. Determination of small dialkyl organophosphonates at microgram/l concentrations in contaminated groundwaters using multiple extraction membrane disks

    Tomkins, B.A.; Griest, W.H. [Oak Ridge National Lab., TN (United States); Hearle, D.R. [Parkdale High School, Riverdale, MD (United States)


    Di-isopropyl methylphosphonate (DIMP) and dimethyl methylphosphonate (DMMP) are byproducts and surrogates for Sarin (GB) and VX; they are readily quantitated at {mu}g/L concentrations in groundwaters. Liter aqueous samples are fortified with triethylphosphate, then passed through a sandwich of 3 preconditioned extraction disks: glass fiber filter to remove particulates, C{sub 18}-based extraction disk to collect DIMP, and carbon-based extraction disk to collect DMMP. The two extraction disks are dried and extracted with MeOH. After the extract is fortified with with diethyl ethylphosphonate internal standard, it is analyzed using a gas chromatograph with a nitrogen- phosphorus detector. When the pump and treat criterion is used, detection limits for DMMP and DIMP are 2 {mu}g/L. Method recovery is 40-50%, based on synthetic groundwaters containing 0.2-50 {mu}g/L of each analyte. DIMP and DMMP are cleanly resolved.

  12. Organophosphonates utilization by soil strains of Ochrobactrum anthropi and Achromobacter sp.

    Ermakova, Inna T; Shushkova, Tatyana V; Sviridov, Alexey V; Zelenkova, Nina F; Vinokurova, Natalya G; Baskunov, Boris P; Leontievsky, Alexey A


    Four bacterial strains from glyphosate- or alkylphosphonates-contaminated soils were tested for ability to utilize different organophosphonates. All studied strains readily utilized methylphosphonic acid and a number of other phosphonates, but differed in their ability to degrade glyphosate. Only strains Ochrobactrum anthropi GPK 3 and Achromobacter sp. Kg 16 utilized this compound after isolation from enrichment cultures with glyphosate. Achromobacter sp. MPK 7 from the same enrichment culture, similar to Achromobacter sp. MPS 12 from methylphosphonate-polluted source, required adaptation to growth on GP. Studied strains varied significantly in their growth parameters, efficiency of phosphonates degradation and characteristic products of this process, as well as in their energy metabolism. These differences give grounds to propose a possible model of interaction between these strains in microbial consortium in phosphonate-contaminated soils.

  13. Synthesis and Herbicidal Activities of Potassium Methyl 1-(Substituted Phenoxyacetoxy)alkylphosphonate

    WANG Tao; WANG Wei; PENG Hao; HE Hong-wu


    A series of potassium methyl 1-(substituted phenoxyacetoxy)alkylphosphonates(9a-9o) was designed and synthesized.The results of preliminary bioassays indicate that most of the title compounds possess excellent pre-emergence and post-emergence herbicidal activities against Brassica napus,Amaranthus mangostanus,Medicago sativa,Echinochloa crusgalli,and Digitaria sanguinalis at a dosage of 1500 g/ha(1 ha=10000 m2).Especially,potassium methyl 1-(2,4-dichlorophenoxyacetoxy)-1-(4-methylphenyl)methylphosphonate(9g) and potassium methyl 1-(2,4-dichlorophenoxyacetoxy)-1-(furan-2-yl)methylphosphonate(9j) show the best herbicidal activity against five tested weeds with more than 85% inhibitory rate in pre-emergence.

  14. Oxidative degradation of chemical warfare agents in water by bleaching powder.

    Qi, Lihong; Zuo, Guomin; Cheng, Zhenxing; Zhu, Haiyan; Li, Shanmao


    Degradation of sulfur mustard (HD), S-2-(di-isopropylamino)ethyl O-ethyl methylphosphonothioate (VX) and Soman (GD) in water by bleaching powder was investigated. The degradation products were comprehensively analyzed by gas chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry (LC/MS) and ion chromatography. Degradation pathways were deduced based on the identified products. The product analysis results indicated that HD could be degraded through oxidation and chlorination reactions, and a small portion of sulfur atoms could be mineralized into SO(4)(2-) ion. Oxidative degradation of VX could finally generate O-ethyl methylphosphonate acid (EMPA), sulfonic acids, SO(4)(2-) and NO(3)(-) ions. GD would be converted into non-toxic pinacolyl methylphosphonate via nucleophilic substitution.

  15. Evidence of VX nerve agent use from contaminated white mustard plants.

    Gravett, Matthew R; Hopkins, Farrha B; Self, Adam J; Webb, Andrew J; Timperley, Christopher M; Baker, Matthew J


    The Chemical Weapons Convention prohibits the development, production, acquisition, stockpiling, retention, transfer or use of chemical weapons by Member States. Verification of compliance and investigations into allegations of use require accurate detection of chemical warfare agents (CWAs) and their degradation products. Detection of CWAs such as organophosphorus nerve agents in the environment relies mainly upon the analysis of soil. We now present a method for the detection of the nerve agent VX and its hydrolysis products by gas chromatography and liquid chromatography mass spectrometry of ethanol extracts of contaminated white mustard plants (Sinapis alba) which retained the compounds of interest for up to 45 days. VX is hydrolysed by the plants to ethyl methylphosphonic acid and then to methylphosphonic acid. The utility of white mustard as a nerve agent detector and remediator of nerve agent-polluted sites is discussed. The work described will help deter the employment of VX in conflict.

  16. Human Health Exposure Assessment for Rocky Mountain Arsenal. Volume 3. Toxicity Assessment Version 4.1


    been reported (EPA, 1979). Some uptake of NDMA in lettuce and spinach grown in hydroponic solutions containing soil, sand, or just water was reported...1973) no hydrolysis of IMPA to methylphosphonic acid (a principal hydrolysis product) was observed after several months in a hydroponic solution. In a...leaves) were analyzed for NDMA content. Lettuce grown in sand had D concentrations of 1.38 mg/kg dry weight and 14.4 mgkg dry weight at 10 and 100 mg

  17. Selective Surface Acoustic Wave-Based Organophosphorus Sensor Employing a Host-Guest Self-Assembly Monolayer of β-Cyclodextrin Derivative.

    Pan, Yong; Mu, Ning; Shao, Shengyu; Yang, Liu; Wang, Wen; Xie, Xiao; He, Shitang


    Self-assembly and molecular imprinting technologies are very attractive technologies for the development of artificial recognition systems and provide chemical recognition based on need and not happenstance. In this paper, we employed a b-cyclodextrin derivative surface acoustic wave (SAW) chemical sensor for detecting the chemical warfare agents (CWAs) sarin (O-Isoprophyl methylphosphonofluoridate, GB). Using sarin acid (isoprophyl hydrogen methylphosphonate) as an imprinting template, mono[6-deoxy-6-[(mercaptodecamethylene)thio

  18. Selective Surface Acoustic Wave-Based Organophosphorus Sensor Employing a Host-Guest Self-Assembly Monolayer of β-Cyclodextrin Derivative

    Yong Pan


    Full Text Available Self-assembly and molecular imprinting technologies are very attractive technologies for the development of artificial recognition systems and provide chemical recognition based on need and not happenstance. In this paper, we employed a b-cyclodextrin derivative surface acoustic wave (SAW chemical sensor for detecting the chemical warfare agents (CWAs sarin (O-Isoprophyl methylphosphonofluoridate, GB. Using sarin acid (isoprophyl hydrogen methylphosphonate as an imprinting template, mono[6-deoxy-6-[(mercaptodecamethylenethio

  19. Halogen-Free Phosphonate Ionic Liquids as Precursors of Abrasion Resistant Surface Layers on AZ31B Magnesium Alloy

    Tulia Espinosa


    Full Text Available Surface coatings formed by immersion in the ionic liquids (ILs 1,3-dimethylimidazolium methylphosphonate (LMP101, 1-ethyl-3-methylimidazolium methylphosphonate (LMP102 and 1-ethyl-3-methylimidazolium ethylphosphonate (LEP102 on magnesium alloy AZ31B at 50 °C have been studied. The purpose of increasing the temperature was to reduce the immersion time, from 14 days at room temperature, to 48 hours at 50 °C. The abrasion resistance of the coated alloy was studied by microscratching under progressively increasing load, and compared with that of the uncoated material. The order of abrasion resistance as a function of the IL is LEP102 > LMP101 > LMP102, which is in agreement with the order obtained for the coatings grown at room temperature. The maximum reduction in penetration depth with respect to the uncovered alloy, of a 44.5%, is obtained for the sample treated with the ethylphosphonate LEP102. However, this reduction is lower than that obtained when the coating is grown at room temperature. This is attributed to the increased thickness and lower adhesion of the coatings obtained at 50 °C, particularly those obtained from methylphosphonate ionic liquids. The results are discussed from SEM-EDX and profilometry.

  20. Determination of S-2-(N,N-diisopropylaminoethyl)- and S-2-(N,N-diethylaminoethyl) methylphosphonothiolate, nerve agent markers, in water samples using strong anion-exchange disk extraction, in vial trimethylsilylation, and gas chromatography-mass spectrometry analysis.

    Subramaniam, Raja; Åstot, Crister; Juhlin, Lars; Nilsson, Calle; Östin, Anders


    Since the establishment of the Chemical Weapons Convention in 1997, the development of analytical methods for unambiguous identification of large numbers of chemicals related to chemical warfare agents has attracted increased interest. The analytically challenging, zwitterionic S-2-(N,N-diisopropylaminoethyl) methylphosphonothiolate (EA-2192), a highly toxic degradation marker of the nerve agent VX, has been reported to resist trimethylsilylation or to result in an unacceptably high limit of detection in GC-MS analysis. In the present study, the problem is demonstrated to be associated with the presence of salt, which hinders trimethysilylation. EA-2192 was extracted from aqueous samples by use of a strong anion-exchange disk, derivatized as a trimethylsilyl derivative via in vial solid-phase trimethylsilylation and identified by GC-MS. The limits of detection were 10 ng/mL and 100 ng/mL (in a water sample) for SIM and SCAN mode respectively. The analytical method was found to be repeatable with relative standard deviation VX and Russian VX, namely S-2-(N,N-diethylaminoethyl) methylphosphonothiolate, ethyl methylphosphonic acid, methylphosphonic acid, and isobutyl methylphosphonic acid. For the synthesis of reference compounds, EA-2192 and its analog from degradation of the Russian VX isomer, the present methods were improved by using a polymer-bound base, resulting in >90% purity based on (1)H NMR. Based on the current results and earlier work on alkylphosphonic acids using the same method, we conclude that the method is a viable choice for the simultaneous determination of a wide range of degradation products of nerve agents - zwitterionic, monoacid, diacid, and monothioacid chemicals - with excellent performance.

  1. Formation of pyrophosphate-like adducts from nerve agents sarin, soman and cyclosarin in phosphate buffer: implications for analytical and toxicological investigations.

    Gäb, Jürgen; John, Harald; Blum, Marc-Michael


    Phosphate buffer is frequently used in biological, biochemical and biomedical applications especially when pH is to be controlled around the physiological value of 7.4. One of the prerequisites of a buffer compound among good buffering capacity and pH stability over time is its non-reactivity with other constituents of the solution. This is especially important for quantitative analytical or toxicological assays. Previous work has identified a number of amino alcohol buffers like TRIS to react with G-type nerve agents sarin, soman and cyclosarin to form stable phosphonic diesters. In case of phosphate buffer we were able to confirm not only the rapid hydrolysis of these agents to the respective alkyl methylphosphonates but also the formation of substantial amounts of pyrophosphate-like adducts (phosphorylated methylphosphonates), which very slowly hydrolyzed following zero-order kinetics. This led to a complex mixture of phosphorus containing species with changing concentrations over time. We identified the molecular structure of these buffer adducts using 1D ¹H-³¹P HSQC NMR and LC-ESI-MS/MS techniques. Reaction rates of adduct formation are fast enough to compete with hydrolysis in aqueous solution and to yield substantial amounts of buffer adduct over the course of just a couple of minutes. Possible reaction mechanisms are discussed with respect to the formation and subsequent hydrolysis of the pyrophosphate-like compounds as well as the increased rate of hydrolysis of the nerve agent to the corresponding alkyl methylphosphonates. In summary, the use of phosphate buffer for the development of new assays with sarin, soman and cyclosarin is discouraged. Already existing protocols should be carefully reexamined on an individual basis.

  2. Efficacy of novel phenoxyalkyl pyridinium oximes as brain-penetrating reactivators of cholinesterase inhibited by surrogates of sarin and VX.

    Chambers, Janice E; Chambers, Howard W; Funck, Kristen E; Meek, Edward C; Pringle, Ronald B; Ross, Matthew K


    Pyridinium oximes are strong nucleophiles and many are effective reactivators of organophosphate-inhibited cholinesterase (ChE). However, the current oxime reactivators are ineffective at crossing the blood-brain barrier and reactivating brain ChE in the intact organism. Our laboratories have developed a series of substituted phenoxyalkyl pyridinium oximes (US patent 9,227,937 B2) with the goal of identifying reactivators effective in crossing the blood-brain barrier. The first 35 of the series were found to have similar in vitro efficacy as reactivators of ChE inhibited by a sarin surrogate (phthalimidyl isopropyl methylphosphonate, PIMP) or a VX surrogate (nitrophenyl ethyl methylphosphonate, NEMP) in bovine brain preparations as previously observed in rat brain preparations. A number of these novel oximes have shown the ability to decrease the level of ChE inhibition in the brains of rats treated with a high sublethal dosage of either a sarin surrogate (nitrophenyl isopropyl methylphosphonate, NIMP) or the VX surrogate NEMP. Levels of reactivation at 2 h after oxime administration were up to 35% while the currently approved therapeutic, 2-PAM, yielded no reduction in brain ChE inhibition. In addition, there was evidence of attenuation of seizure-like behavior with several of the more effective novel oximes, but not 2-PAM. Therefore these novel oximes have demonstrated an ability to reactivate inhibited ChE in brain preparations from two species and in vivo data support their ability to enter the brain and provide a therapeutic action. These novel oximes have the potential to be developed into improved antidotes for nerve agent therapy.

  3. Complex of Burkholderia cepacia lipase with transition state analogue of 1-phenoxy-2-acetoxybutane: biocatalytic, structural and modelling study.

    Luić, M; Tomić, S; Lescić, I; Ljubović, E; Sepac, D; Sunjić, V; Vitale, L; Saenger, W; Kojic-Prodić, B


    In a series of four racemic phenoxyalkyl-alkyl carbinols, 1-phenoxy-2-hydroxybutane (1) is enantioselectively acetylated by Burkholderia cepacia (formerly Pseudomonas cepacia) lipase with an E value > or = 200, whereas for the other three racemates E was found to be analogue with a tetrahedral P-atom, (R(P),S(P))-O-(2R)-(1-phenoxybut-2-yl)methylphosphonic acid chloride was prepared and crystallized in complex with B. cepacia lipase. The X-ray structure of the complex was determined, allowing to compare the conformation of the inhibitor with results of molecular modelling.

  4. Acquisition of an X-Ray Diffractometer with WAXS and SAXS for Materials Research


    exposure to 2-chloroethyl ethylsulfide (CEES) and dimethyl methylphosphonate (DMMP) as chemical warfare agent simulants will be investigated. In...2,3,3΄,4΄-biphenyltetracarboxylic dianhydride (s-BPDA), 1,3,-bis(3-aminophenoxy) benzene (1,3,3-APB), 3,4΄-oxydianliline (3,4΄-ODA) and end- capped with... benzene (1,3,4-APB) and m-phenylendiamine (m–PDA), and a PEPA end-cap. RTM 370 is formulated with a-BPDA, 3,4’-oxydianinline (3,4’-ODA) and

  5. Intermediates in the transformation of phosphonates to phosphate by bacteria.

    Kamat, Siddhesh S; Williams, Howard J; Raushel, Frank M


    Phosphorus is an essential element for all known forms of life. In living systems, phosphorus is an integral component of nucleic acids, carbohydrates and phospholipids, where it is incorporated as a derivative of phosphate. However, most Gram-negative bacteria have the capability to use phosphonates as a nutritional source of phosphorus under conditions of phosphate starvation. In these organisms, methylphosphonate is converted to phosphate and methane. In a formal sense, this transformation is a hydrolytic cleavage of a carbon-phosphorus (C-P) bond, but a general enzymatic mechanism for the activation and conversion of alkylphosphonates to phosphate and an alkane has not been elucidated despite much effort for more than two decades. The actual mechanism for C-P bond cleavage is likely to be a radical-based transformation. In Escherichia coli, the catalytic machinery for the C-P lyase reaction has been localized to the phn gene cluster. This operon consists of the 14 genes phnC, phnD, …, phnP. Genetic and biochemical experiments have demonstrated that the genes phnG, phnH, …, phnM encode proteins that are essential for the conversion of phosphonates to phosphate and that the proteins encoded by the other genes in the operon have auxiliary functions. There are no functional annotations for any of the seven proteins considered essential for C-P bond cleavage. Here we show that methylphosphonate reacts with MgATP to form α-D-ribose-1-methylphosphonate-5-triphosphate (RPnTP) and adenine. The triphosphate moiety of RPnTP is hydrolysed to pyrophosphate and α-D-ribose-1-methylphosphonate-5-phosphate (PRPn). The C-P bond of PRPn is subsequently cleaved in a radical-based reaction producing α-D-ribose-1,2-cyclic-phosphate-5-phosphate and methane in the presence of S-adenosyl-L-methionine. Substantial quantities of phosphonates are produced worldwide for industrial processes, detergents, herbicides and pharmaceuticals. Our elucidation of the chemical steps for the

  6. イミノ二メチルホスホン酸型キトサン樹脂の合成と微量金属の捕集挙動

    山川, 聡子; 大下, 浩司; ,; 大島, 光子; 本水, 昌二


    A chitosan-based resin possessing the iminodi(methylphosphonic acid) moiety (IDP-type chitosan resin) was synthesized by using cross-linked chitosan as a base material. The adsorption behavior of trace metal ions on the IDP-type chitosan resin was systematically investigated using a mini-column (1 ml of the resin) packed with the resin. The concentrations of metal ions in the effluents were measured by ICP-MS and ICP-AES. The resin could adsorb four metals, such as In(III), Sn(II), Th(IV), an...

  7. Analysis of VX nerve agent hydrolysis products in wastewater effluents by ion chromatography with amperometric and conductivity detection.

    Piao, Haishan; Marx, Randall B; Schneider, Steven; Irvine, David A; Staton, John


    An analytical method, based on the use of ion chromatography, was developed to monitor the levels of three regulated VX hydrolysis products in the effluent from a biological wastewater treatment process--ethylmethylphosphonic acid, methylphosphonic acid and 2-(diisopropyl)aminoethanethiol. Previous methods have not been applied to wastewater matrices or 2-(diisopropyl)aminoethanethiol. Despite the specificity and sensitivity constraints of this method, it was possible to measure the compounds in bioreactor effluents down to a level substantially below the US Army discharge limit of 0.1% (w/v). Analytical data was confirmed by liquid chromatography-mass spectrometry (LC-MS) at an independent laboratory.

  8. TG-FTIR characterization of flame retardant polyurethane foams materials

    Liu, W.; Tang, Y.; Li, F.; Ge, X. G.; Zhang, Z. J.


    Dimethyl methylphosphonate (DMMP) and trichloroethyl phosphtate (TCEP) have been used to enhance the flame retardancy of polyurethane foams materials (PUF). Flame retardancy and thermal degradation of PUF samples have been investigated by the LOI tests and thermal analysis. The results indicate that the excellent flame retardancy can be achieved due to the presence of the flame retardant system containing DMMP and TCEP. TG-FTIR reveals that the addition of DMMP/TCEP can not only improve the thermal stability of PUF samples but can also affect the gaseous phase at high temperature.

  9. Exploring the aryl esterase catalysis of paraoxonase-1 through solvent kinetic isotope effects and phosphonate-based isosteric analogues of the tetrahedral reaction intermediate.

    Bavec, Aljoša; Knez, Damijan; Makovec, Tomaž; Stojan, Jure; Gobec, Stanislav; Goličnik, Marko


    Although a recent study of Debord et al. in Biochimie (2014; 97:72-77) described the thermodynamics of the catalysed hydrolysis of phenyl acetate by human paraoxonase-1, the mechanistic details along the reaction route of this enzyme remain unclear. Therefore, we briefly present the solvent kinetic isotope effects on the phenyl acetate esterase activity of paraoxonase-1 and its inhibition with the phenyl methylphosphonate anion, which is a stable isosteric analogue that mimics the high-energy tetrahedral intermediate on the hydroxide-promoted hydrolysis pathway. The data show normal isotope effects, while proton inventory analysis indicates that two protons contribute to the kinetic isotope effect. Coherently, moderate competitive inhibition with the phenyl methylphosphonate anion reveals that the rate-limiting transition state suboptimally resembles the tetrahedral intermediate. The implications of these findings can be attributed to two possible reaction mechanisms that might occur during the paraoxonase-1-catalysed hydrolysis of phenyl acetate. Copyright © 2014 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

  10. Method Of Signal Amplification In Multi-Chromophore Luminescence Sensors

    Levitsky, Igor A. (Fall River, MA); Krivoshlykov, Sergei G. (Shrewsbury, MA)


    A fluorescence-based method for highly sensitive and selective detection of analyte molecules is proposed. The method employs the energy transfer between two or more fluorescent chromophores in a carefully selected polymer matrix. In one preferred embodiment, signal amplification has been achieved in the fluorescent sensing of dimethyl methylphosphonate (DMMP) using two dyes, 3-aminofluoranthene (AM) and Nile Red (NR), in a hydrogen bond acidic polymer matrix. The selected polymer matrix quenches the fluorescence of both dyes and shifts dye emission and absorption spectra relative to more inert matrices. Upon DMMP sorption, the AM fluorescence shifts to the red at the same time the NR absorption shifts to the blue, resulting in better band overlap and increased energy transfer between chromophores. In another preferred embodiment, the sensitive material is incorporated into an optical fiber system enabling efficient excitation of the dye and collecting the fluorescent signal form the sensitive material on the remote end of the system. The proposed method can be applied to multichromophore luminescence sensor systems incorporating N-chromophores leading to N-fold signal amplification and improved selectivity. The method can be used in all applications where highly sensitive detection of basic gases, such as dimethyl methylphosphonate (DMMP), Sarin, Soman and other chemical warfare agents having basic properties, is required, including environmental monitoring, chemical industry and medicine.

  11. Trace analysis of organics in air by corona discharge atmospheric pressure ionization using an electrospray ionization interface.

    Nikolaev, Eugene; Riter, Leah S; Laughlin, Brian C; Handberg, Eric; Cooks, R Graham


    A corona discharge ion source operating at atmospheric pressure in the point-to-plane configuration was constructed by reconfiguring the ion source of a commercial electrospray ionization (ESI) quadrupole mass spectrometer. This new source allows direct air analysis without modification to the mass spectrometer. Detection and quantitation of semi-volatile compounds in air is demonstrated. The analytical performance of the system was established using the chemical warfare agent simulants methyl salicylate and dimethyl methylphosphonate. Limits of detection are 60 pptr in the negative-ion mode and 800 pptr in the positive-ion mode for methyl salicylate and 800 pptr in the negative-ion mode and 3.6 ppb in the positive-ion mode for dimethyl methylphosphonate. A linear response was observed from 60 pptr to 8 ppb for methyl salicylate in air in the negative-ionization mode. Cluster ion formation versus production of analyte ions was investigated and it was found that dry air or an elevated capillary interface temperature (130 degrees C) was needed to avoid extensive clustering, mostly of water. Reagent gases are not needed as proton sources, as is usually the case for atmospheric pressure chemical ionization, and this, together with the simplicity, sensitivity and speed of the technique, makes it promising for miniaturization and future field studies.

  12. Ion-molecule reactions of O,S-dimethyl methylphosphonothioate: evidence for intramolecular sulfur oxidation during VX perhydrolysis.

    McAnoy, Andrew M; Williams, Jilliarne; Paine, Martin R L; Rogers, Michael L; Blanksby, Stephen J


    The alkaline perhydrolysis of the nerve agent O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) was investigated by studying the ion-molecule reactions of HOO(-) with O,S-dimethyl methylphosphonothioate in a modified linear ion-trap mass spectrometer. In addition to simple proton transfer, two other abundant product ions are observed at m/z 125 and 109 corresponding to the S-methyl methylphosphonothioate and methyl methylphosphonate anions, respectively. The structure of these product ions is demonstrated by a combination of collision-induced dissociation and isotope-labeling experiments that also provide evidence for their formation by nucleophilic reaction pathways, namely, (i) S(N)2 at carbon to yield the S-methyl methylphosphonothioate anion and (ii) nucleophilic addition at phosphorus affording a reactive pentavalent intermediate that readily undergoes internal sulfur oxidation and concomitant elimination of CH(3)SOH to yield the methyl methylphosphonate anion. Consistent with previous solution phase observations of VX perhydrolysis, the toxic P-O cleavage product is not observed in this VX model system and theoretical calculations identify P-O cleavage to be energetically uncompetitive. Conversely, intramolecular sulfur oxidation is calculated to be extremely exothermic and kinetically accessible explaining its competitiveness with the facile gas phase proton transfer process. Elimination of a sulfur moiety deactivates the nerve agent VX and thus the intramolecular sulfur oxidation process reported here is also able to explain the selective perhydrolysis of the nerve agent to relatively nontoxic products.

  13. Novel nucleophiles enhance the human serum paraoxonase 1 (PON1)-mediated detoxication of organophosphates.

    Chambers, Janice E; Chambers, Howard W; Meek, Edward C; Funck, Kristen E; Bhavaraju, Manikanthan H; Gwaltney, Steven R; Pringle, Ronald B


    Paraoxonase 1 (PON1) is a calcium-dependent hydrolase associated with serum high-density lipoprotein particles. PON1 hydrolyzes some organophosphates (OPs), including some nerve agents, through nucleophilic attack of hydroxide ion (from water) in the active site. Most OPs are hydrolyzed inefficiently. This project seeks to identify nucleophiles that can enhance PON1-mediated OP degradation. A series of novel nucleophiles, substituted phenoxyalkyl pyridinium oximes, has been synthesized which enhance the degradation of surrogates of sarin (nitrophenyl isopropyl methylphosphonate; NIMP) and VX (nitrophenyl ethyl methylphosphonate; NEMP). Two types of in vitro assays have been conducted, a direct assay using millimolar concentrations of substrate with direct spectrophotometric quantitation of a hydrolysis product (4-nitrophenol) and an indirect assay using submicromolar concentrations of substrate with quantitation by the level of inhibition of an exogenous source of acetylcholinesterase from non-hydrolyzed substrate. Neither NIMP nor NEMP is hydrolyzed effectively by PON1 if one of these novel oximes is absent. However, in the presence of eight novel oximes, PON1-mediated degradation of both surrogates occurs. Computational modeling has created a model of PON1 embedded in phospholipid and has indicated general agreement of the binding enthalpies with the relative efficacy as PON1 enhancers. PON1 enhancement of degradation of OPs could be a unique and unprecedented mechanism of antidotal action.

  14. On-matrix Derivatization for Dynamic Headspace Sampling of Nonvolatile Surface Residues

    Harvey, Scott D.; Wahl, Jon H.


    The goal of this study is to extend sampling by the field and laboratory emission cell (FLEC) purge-and-trap technique to applications that target nonvolatile residues. On-matrix derivatization of residues to render analytes stable and more volatile is explored to achieve this goal. Results show that on-matrix derivatizations of nerve agent hydrolysis products (monoalkyl methylphosphonic acids and methylphosphonic acid [MPA]) with diazomethane were successful on glass and painted wallboard (at the 10-µg level). It also was successful on the more difficult concrete (at the 500-µg level) and carpet (at the 20-µg level) substrates that cannot be successfully sampled using swipe techniques. Analysis of additional chemical warfare (CW)-associated residues can be approached by on-matrix derivatization with trifluoroacetic anhydride (TFAA). For example, amines (used as stabilizers or present as decomposition products of the nerve agent VX) or thiodiglycol (hydrolysis product of sulfur mustard) could be sampled as their TFAA derivatives from glass, painted wallboard, and concrete (at the 40-µg level), as well as carpet (at the 80-µg level) surfaces. Although the amine and thiodiglycol are semi-volatile and could be sampled directly, derivatization improves the recovery and chromatographic behavior of these analytes.

  15. On-matrix derivatization for dynamic headspace sampling of nonvolatile surface residues.

    Harvey, Scott D; Wahl, Jon H


    The goal of this study is to extend sampling by the field and laboratory emission cell (FLEC) dynamic headspace technique to applications that target nonvolatile residues. On-matrix derivatization of residues to render analytes stable and more volatile is explored to achieve this goal. Results show that on-matrix derivatizations of nerve agent hydrolysis products (monoalkyl methylphosphonic acids and methylphosphonic acid [MPA]) with diazomethane were successful on glass and painted wallboard (at the 10-μg level). It also was successful on the more difficult concrete (at the 500-μg level) and carpet (at the 20-μg level), substrates that cannot be successfully sampled using swipe techniques. Analysis of additional chemical warfare (CW)-associated residues can be approached by on-matrix derivatization with trifluoroacetic anhydride (TFAA). For example, amines (used as stabilizers or present as decomposition products of the nerve agent VX) or thiodiglycol (hydrolysis product of sulfur mustard) could be sampled as their TFAA derivatives from glass, painted wallboard, and concrete (at the 40-μg level), as well as carpet (at the 80-μg level) surfaces. Although the amine and thiodiglycol are semi-volatile and could be sampled directly, derivatization improves the recovery and chromatographic behavior of these analytes.

  16. Fate of the chemical warfare agent O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate (VX) on soil following accelerant-based fire and liquid decontamination.

    Gravett, M R; Hopkins, F B; Self, A J; Webb, A J; Timperley, C M; Riches, J R


    In the event of alleged use of organophosphorus nerve agents, all kinds of environmental samples can be received for analysis. These might include decontaminated and charred matter collected from the site of a suspected chemical attack. In other scenarios, such matter might be sampled to confirm the site of a chemical weapon test or clandestine laboratory decontaminated and burned to prevent discovery. To provide an analytical capability for these contingencies, we present a preliminary investigation of the effect of accelerant-based fire and liquid decontamination on soil contaminated with the nerve agent O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate (VX). The objectives were (a) to determine if VX or its degradation products were detectable in soil after an accelerant-based fire promoted by aviation fuel, including following decontamination with Decontamination Solution 2 (DS2) or aqueous sodium hypochlorite, (b) to develop analytical methods to support forensic analysis of accelerant-soaked, decontaminated and charred soil and (c) to inform the design of future experiments of this type to improve analytical fidelity. Our results show for the first time that modern analytical techniques can be used to identify residual VX and its degradation products in contaminated soil after an accelerant-based fire and after chemical decontamination and then fire. Comparison of the gas chromatography-mass spectrometry (GC-MS) profiles of VX and its impurities/degradation products from contaminated burnt soil, and burnt soil spiked with VX, indicated that the fire resulted in the production of diethyl methylphosphonate and O,S-diethyl methylphosphonothiolate (by an unknown mechanism). Other products identified were indicative of chemical decontamination, and some of these provided evidence of the decontaminant used, for example, ethyl 2-methoxyethyl methylphosphonate and bis(2-methoxyethyl) methylphosphonate following decontamination with DS2. Sample preparation

  17. Effective methylation of phosphonic acids related to chemical warfare agents mediated by trimethyloxonium tetrafluoroborate for their qualitative detection and identification by gas chromatography-mass spectrometry.

    Valdez, Carlos A; Leif, Roald N; Alcaraz, Armando


    The effective methylation of phosphonic acids related to chemical warfare agents (CWAs) employing trimethyloxonium tetrafluoroborate (TMO·BF4) for their qualitative detection and identification by gas chromatography-mass spectrometry (GC-MS) is presented. The methylation occurs in rapid fashion (1 h) and can be conveniently carried out at ambient temperature, thus providing a safer alternative to the universally employed diazomethane-based methylation protocols. Optimization of the methylation parameters led us to conclude that methylene chloride was the ideal solvent to carry out the derivatization, and that even though methylated products can be observed surfacing after only 1 h, additional time was not found to be detrimental but beneficial to the process particularly when dealing with analytes at low concentrations (∼10 μg mL(-1)). Due to its insolubility in methylene chloride, TMO·BF4 conveniently settles to the bottom during the reaction and does not produce additional interfering by-products that may further complicate the GC-MS analysis. The method was demonstrated to successfully methylate a variety of Schedule 2 phosphonic acids, including their half esters, resulting in derivatives that were readily detected and identified using the instrument's spectral library. Most importantly, the method was shown to simultaneously methylate a mixture of the organophosphorus-based nerve agent hydrolysis products: pinacolyl methylphosphonate (PMPA), cyclohexyl methylphosphonate (CyMPA) and ethyl methylphosphonate (EMPA) (at a 10 μg mL(-1) concentration each) in a fatty acid ester-rich organic matrix (OPCW-PT-O3) featured in the 38th Organisation for the Prohibition of Chemical Weapons (OPCW) Proficiency Test. In addition, the protocol was found to effectively methylate N,N-diethylamino ethanesulfonic acid and N,N-diisopropylamino ethanesulfonic acid that are products arising from the oxidative degradation of the V-series agents VR and VX respectively. The

  18. Impurity Profiling to Match a Nerve Agent to Its Precursor Source for Chemical Forensics Applications

    Fraga, Carlos G.; Perez Acosta, Gabriel A.; Crenshaw, Michael D.; Wallace, Krys; Mong, Gary M.; Colburn, Heather A.


    Chemical forensics is an emerging field in homeland security that aims to attribute a weaponized toxic chemical or related material to its source. Herein, for the first time, trace impurities originating from a chemical precursor were used to match a synthesized nerve agent to its precursor source. Specifically, multiple batches of sarin and its intermediate were synthesized from two commercial stocks of methylphosphonic dichloride (DC) and were then matched by impurity profiling to their DC stocks from out of five possible stocks. This was possible because each DC stock had a unique impurity profile that, for the tested stocks, persisted through synthesis, decontamination, and sample preparation. This work may form a basis for using impurity profiling to help find and prosecute perpetrators of chemical attacks.

  19. Effect of Spacer and the Enzyme-Linked Immunosorbent Assay

    Manisha Sathe


    Full Text Available The effect of spacers and the enzyme-linked immunosorbent assay (ELISA formats on the functional parameters of assays such as lower detection limit, inhibitory concentration at 50 per cent (IC50, and specificity were studied. Enzyme conjugates having hydrophobic and hydrophilic spacers were prepared using O-isopropyl methylphosphonic acid (IMPA and horseradish peroxidase (HRP as an enzyme label. Comparison was made with reference to enzyme conjugate without any spacer. The present investigation revealed that the presence of a hydrophilic spacer in the enzyme conjugate significantly improves the sensitivity of assays. An enhanced IC50 value achieved was 0.01 μg mL−1 for free antigen detection by direct immunoassay using hydrophilic spacers and precoating of ELISA plates by secondary antibody. The use of a hydrophilic spacer might have helped in projecting the hapten in the aqueous phase, leading to enhanced antibody binding signal and improved sensitivity of the assay.

  20. Trapping of organophosphorus chemical nerve agents in water with amino acid functionalized baskets.

    Ruan, Yian; Dalkiliç, Erdin; Peterson, Paul W; Pandit, Aroh; Dastan, Arif; Brown, Jason D; Polen, Shane M; Hadad, Christopher M; Badjić, Jovica D


    We prepared eleven amino-acid functionalized baskets and used (1) H NMR spectroscopy to quantify their affinity for entrapping dimethyl methylphosphonate (DMMP, 118 Å(3) ) in aqueous phosphate buffer at pH=7.0±0.1; note that DMMP guest is akin in size to chemical nerve agent sarin (132 Å(3) ). The binding interaction (Ka ) was found to vary with the size of substituent groups at the basket's rim. In particular, the degree of branching at the first carbon of each substituent had the greatest effect on the host-guest interaction, as described with the Verloop's B1 steric parameter. The branching at the remote carbons, however, did not perturb the encapsulation, which is important for guiding the design of more effective hosts and catalysts in future.

  1. Decomposition of adsorbed VX on activated carbons studied by 31P MAS NMR.

    Columbus, Ishay; Waysbort, Daniel; Shmueli, Liora; Nir, Ido; Kaplan, Doron


    The fate of the persistent OP nerve agent O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) on granular activated carbons that are used for gas filtration was studied by means of 31P magic angle spinning (MAS) NMR spectroscopy. VX as vapor or liquid was adsorbed on carbon granules, and MAS NMR spectra were recorded periodically. The results show that at least 90% of the adsorbed VX decomposes within 20 days or less to the nontoxic ethyl methylphosphonic acid (EMPA) and bis(S-2-diisopropylaminoethane) {(DES)2}. Decomposition occurred irrespective of the phase from which VX was loaded, the presence of metal impregnation on the carbon surface, and the water content of the carbon. Theoretical and practical aspects of the degradation are discussed.

  2. Identification of metabolites of nerve agent VX in serum collected from a victim.

    Tsuchihashi, H; Katagi, M; Nishikawa, M; Tatsuno, M


    A human serum sample collected from a victim of the Osaka VX incident was analyzed according to our developed technique for metabolites of VX. Gas chromatography-mass spectrometry (GC-MS) in full-scan electron impact and chemical ionization modes were used, and, for more reliable confirmation, GC-MS-MS was also employed. In the serum sample, both ethyl methylphosphonic acid and 2-(diisopropylamino-ethyl)methyl sulfide were detected. These results indicated that the techniques using GC-MS and GC-MS-MS were applicable to biological samples such as serum. These results also provide the first documented, unequivocal identification of the specific metabolites of VX in victim's serum and, furthermore, clarify a part of the metabolic pathway of VX in the human body.

  3. Interactions of phosphororganic agents with water and components of polyelectrolyte membranes.

    Lee, Ming-Tsung; Vishnyakov, Aleksey; Gor, Gennady Yu; Neimark, Alexander V


    Interactions of nerve G-agents (sarin and soman) and their simulants DMMP (dimethyl methylphosphonate) and DIFP (diisopropyl fluorophosphate) with water and components of polyelectrolyte membranes are studied using ab initio calculations in conjunction with thermodynamic modeling using the conductor-like screening model for real solvents (COSMO-RS). To test reliability of COSMO-RS calculations, we measured the vapor-liquid equilibrium in DMMP-water mixtures and found quantitative agreement between computed and experimental results. Using COSMO-RS, we studied the interactions of phosphororganic agents with the characteristic fragments of perfluorinated and sulfonated polystyrene (sPS) polyelectrolytes, which are explored for protective clothing membranes. We found that both simulants, DIFP and DMMP, mimic the thermodynamic properties of G-agents reasonably well; however, there are certain specific differences that are discussed. We also suggested that sPS-based polyelectrolytes have less affinity for phosphorganic agents compared to prefluorinated polyelectrolytes similar to Nafion.

  4. Next generation hazard detection via ultrafast coherent anti-Stokes Raman spectroscopy

    Brady, John J.; Pellegrino, Paul M.


    Multiplex coherent anti-Stokes Raman spectroscopy (MCARS) is used to detect an explosive precursor material and two chemical warfare simulants. The spectral bandwidth of the femtosecond laser pulse used in these studies is sufficient to coherently and simultaneously drive all the vibrational modes in the molecule of interest. The research performed here demonstrates that MCARS has the capability to detect an explosive precursor (e.g., acetone) and hazardous materials, such as dimethyl methylphosphonate and 2-chloroethyl methyl sulfide (a sarin and a mustard gas chemical warfare simulant, respectively), with high specificity. Evidence shows that MCARS is capable of overcoming common the sensitivity limitations of spontaneous Raman scattering, thus allowing for the detection of the target material in milliseconds with standard USB spectrometers as opposed to seconds with intensified spectrometers. The exponential increase in the number of scattered photons suggests that the MCARS technique may be capable of overcoming range detection challenges common to spontaneous Raman scattering.

  5. Decontamination of adsorbed chemical warfare agents on activated carbon using hydrogen peroxide solutions.

    Osovsky, Ruth; Kaplan, Doron; Nir, Ido; Rotter, Hadar; Elisha, Shmuel; Columbus, Ishay


    Mild treatment with hydrogen peroxide solutions (3-30%) efficiently decomposes adsorbed chemical warfare agents (CWAs) on microporous activated carbons used in protective garments and air filters. Better than 95% decomposition of adsorbed sulfur mustard (HD), sarin, and VX was achieved at ambient temperatures within 1-24 h, depending on the H2O2 concentration. HD was oxidized to the nontoxic HD-sulfoxide. The nerve agents were perhydrolyzed to the respective nontoxic methylphosphonic acids. The relative rapidity of the oxidation and perhydrolysis under these conditions is attributed to the microenvironment of the micropores. Apparently, the reactions are favored due to basic sites on the carbon surface. Our findings suggest a potential environmentally friendly route for decontamination of adsorbed CWAs, using H2O2 without the need of cosolvents or activators.

  6. Response Mechanism for Surface Acoustic Wave Gas Sensors Based on Surface-Adsorption

    Jiansheng Liu


    Full Text Available A theoretical model is established to describe the response mechanism of surface acoustic wave (SAW gas sensors based on physical adsorption on the detector surface. Wohljent’s method is utilized to describe the relationship of sensor output (frequency shift of SAW oscillator and the mass loaded on the detector surface. The Brunauer-Emmett-Teller (BET formula and its improved form are introduced to depict the adsorption behavior of gas on the detector surface. By combining the two methods, we obtain a theoretical model for the response mechanism of SAW gas sensors. By using a commercial SAW gas chromatography (GC analyzer, an experiment is performed to measure the frequency shifts caused by different concentration of dimethyl methylphosphonate (DMMP. The parameters in the model are given by fitting the experimental results and the theoretical curve agrees well with the experimental data.

  7. Catalytic degradation of the nerve agent VX by water-swelled polystyrene-supported ammonium fluorides.

    Marciano, Daniele; Goldvaser, Michael; Columbus, Ishay; Zafrani, Yossi


    The catalytic degradation of the nerve agent VX (O-ethyl S-2-(diisopropylamino)ethyl methylphosphonothioate) by water-swelled polymer-supported ammonium fluorides is described. VX (0.06-0.53 mol/mol F(-)) is rapidly degraded (t(1/2) ∼ 10-30 min) to form the "G-analogue" (O-ethyl methylphosphonofluoridate), which hydrolyzes (t(1/2) ∼ 1-1.5 h) to the nontoxic EMPA (ethyl methylphosphonic acid). The toxic desethyl-VX is not formed. The catalytic effect of fluoride is maintained even when 6 equiv of VX are loaded. GB (O-isopropyl methylphosphonofluoridate) and desethyl-VX agents are also degraded under these conditions.

  8. Decomposition of adsorbed VX on activated carbons studied by {sup 31}P MAS NMR

    Ishay Columbus; Daniel Waysbort; Liora Shmueli; Ido Nir; Doron Kaplan [Israel Institute for Biological Research, Ness Ziona (Israel). Departments of Organic Chemistry and Physical Chemistry


    The fate of the persistent OP nerve agent O-ethyl S-(2-(diisopropylamino)ethyl) methylphosphonothioate (VX) on granular activated carbons that are used for gas filtration was studied by means of 31P magic angle spinning (MAS) NMR spectroscopy. Four types of activated carbon were used, including coal-based BPL. VX as vapor or liquid was adsorbed on carbon granules, and MAS NMR spectra were recorded periodically. The results show that at least 90% of the adsorbed VX decomposes within 20 days or less to the nontoxic ethyl methylphosphonic acid (EMPA) and bis(S-2-diisopropylaminoethane) ((DES){sub 2}). Decomposition occurred irrespective of the phase from which VX was loaded, the presence of metal impregnation on the carbon surface, and the water content of the carbon. Theoretical and practical aspects of the degradation are discussed. 17 refs., 6 figs., 3 tabs.

  9. Hand-held analyser based on microchip electrophoresis with contactless conductivity detection for measurement of chemical warfare agent degradation products

    Duran, Karolina-Petkovic; Zhu, Yonggang; Chen, Chuanpin; Swallow, Anthony; Stewart, Robert; Hoobin, Pam; Leech, Patrick; Ovenden, Simon


    This paper reports on the development of a hand-held device for on-site detection of organophosphonate nerve agent degradation products. This field-deployable analyzer relies on efficient microchip electrophoresis separation of alkyl methylphosphonic acids and their sensitive contactless conductivity detection. Miniaturized, low-powered design is coupled with promising analytical performance for separating the breakdown products of chemical warfare agents such as Soman, Sarin and VX . The detector has a detection limit of about 10 μg/mL and has a good linear response in the range 10-300 μg/mL concentration range. Applicability to environmental samples is demonstrated .The new hand-held analyzer offers great promise for converting conventional ion chromatography or capillary electrophoresis sophisticated systems into a portable forensic laboratory for faster, simpler and more reliable on-site screening.

  10. Graphene oxide as sensitive layer in Love-wave surface acoustic wave sensors for the detection of chemical warfare agent simulants.

    Sayago, Isabel; Matatagui, Daniel; Fernández, María Jesús; Fontecha, José Luis; Jurewicz, Izabela; Garriga, Rosa; Muñoz, Edgar


    A Love-wave device with graphene oxide (GO) as sensitive layer has been developed for the detection of chemical warfare agent (CWA) simulants. Sensitive films were fabricated by airbrushing GO dispersions onto Love-wave devices. The resulting Love-wave sensors detected very low CWA simulant concentrations in synthetic air at room temperature (as low as 0.2 ppm for dimethyl-methylphosphonate, DMMP, a simulant of sarin nerve gas, and 0.75 ppm for dipropylene glycol monomethyl ether, DPGME, a simulant of nitrogen mustard). High responses to DMMP and DPGME were obtained with sensitivities of 3087 and 760 Hz/ppm respectively. Very low limit of detection (LOD) values (9 and 40 ppb for DMMP and DPGME, respectively) were calculated from the achieved experimental data. The sensor exhibited outstanding sensitivity, good linearity and repeatability to all simulants tested. The detection mechanism is here explained in terms of hydrogen bonding formation between the tested CWA simulants and GO.

  11. Chemical vapor detection using a capacitive micromachined ultrasonic transducer.

    Lee, Hyunjoo J; Park, Kwan Kyu; Kupnik, Mario; Oralkan, O; Khuri-Yakub, Butrus T


    Distributed sensing of gas-phase chemicals using highly sensitive and inexpensive sensors is of great interest for many defense and consumer applications. In this paper we present ppb-level detection of dimethyl methylphosphonate (DMMP), a common simulant for sarin gas, with a ppt-level resolution using an improved capacitive micromachined ultrasonic transducer (CMUT) as a resonant chemical sensor. The improved CMUT operates at a higher resonant frequency of 47.7 MHz and offers an improved mass sensitivity of 48.8 zg/Hz/μm(2) by a factor of 2.7 compared to the previous CMUT sensors developed. A low-noise oscillator using the CMUT resonant sensor as the frequency-selective device was developed for real-time sensing, which exhibits an Allan deviation of 1.65 Hz (3σ) in the presence of a gas flow; this translates into a mass resolution of 80.5 zg/μm(2). The CMUT resonant sensor is functionalized with a 50-nm thick DKAP polymer developed at Sandia National Laboratory for dimethyl methylphosphonate (DMMP) detection. To demonstrate ppb-level detection of the improved chemical sensor system, the sensor performance was tested at a certified lab (MIT Lincoln Laboratory), which is equipped with an experimental chemical setup that reliably and accurately delivers a wide range of low concentrations down to 10 ppb. We report a high volume sensitivity of 34.5 ± 0.79 pptv/Hz to DMMP and a good selectivity of the polymer to DMMP with respect to dodecane and 1-octanol.

  12. Dust as a collection media for contaminant source attribution.

    Favela, Kristin Herrmann; Bohmann, Jonathan A; Williamson, William S


    Dust was investigated for its ability to retain source attribution profiles (SAPs) after chemical exposure. Three distinct sources of the organophosphate pesticide acephate were investigated as a proof-of-concept model. In addition, attribution profiles were created and tested using compounds related to chemical warfare agents (CWAs), specifically VX and G-series agents: O-ethyl methylphosphonothioate (EMPTA), N,N-diisopropylmethylamine (DIPMA), N,N-diisopropylethylamine (DIEA), diisopropylamine (DIPA), diethyl aniline (DEA), diethyl ethyl phosphonate (DEEP), trimethyl phosphite (TMP), dimethyl hydrogen phosphite (DMHP), diethyl hydrogen phosphite (DEHP), triethyl phosphate (TEP), ethyl methylphosphonate (EMPA), and diisopropyl methylphosphonate (DIMP). Dust was collected from a storage shed, aliquots deposited on carpet and loaded with distinct chemical profiles using an exposure chamber and aerosolizer. After a given period of time (1h, 24h, or 72 h), the dust was extracted and its SAP analyzed by gas chromatography-mass spectrometry (GC-MS) and/or liquid chromatography-tandem mass spectrometry (LC-MS/MS). Principal components analysis (PCA) was used to determine the association of dust exposed to the same and different chemical sources. PCA results demonstrate that dust samples exposed to distinct chemical sources are clearly differentiated from one another across all collection times. Furthermore, dust aliquots exposed to the same source can be clearly associated with one another across all collection times. When the CWA-related compounds were subjected to elevated temperature (90°C) conditions, it was found that the signature was stable at the 1h and 24h collections. At 72 h and elevated temperature, larger deviations from the control were observed for some compounds. Elevated pH (10) affected the profile to a lesser degree than elevated temperature. Overall, dust is found to be an effective media for the in situ collection of source attribution profiles.

  13. Variants of Phosphotriesterase for the Enhanced Detoxification of the Chemical Warfare Agent VR.

    Bigley, Andrew N; Mabanglo, Mark F; Harvey, Steven P; Raushel, Frank M


    The V-type organophosphorus nerve agents are among the most hazardous compounds known. Previous efforts to evolve the bacterial enzyme phosphotriesterase (PTE) for the hydrolytic decontamination of VX resulted in the identification of the variant L7ep-3a, which has a kcat value more than 2 orders of magnitude higher than that of wild-type PTE for the hydrolysis of VX. Because of the relatively small size of the O-ethyl, methylphosphonate center in VX, stereoselectivity is not a major concern. However, the Russian V-agent, VR, contains a larger O-isobutyl, methylphosphonate center, making stereoselectivity a significant issue since the SP-enantiomer is expected to be significantly more toxic than the RP-enantiomer. The three-dimensional structure of the L7ep-3a variant was determined to a resolution of 2.01 Å (PDB id: 4ZST ). The active site of the L7ep-3a mutant has revealed a network of hydrogen bonding interactions between Asp-301, Tyr-257, Gln-254, and the hydroxide that bridges the two metal ions. A series of new analogues that mimic VX and VR has helped to identify critical structural features for the development of new enzyme variants that are further enhanced for the catalytic detoxification of VR and VX. The best of these mutants has been shown to have a reversed stereochemical preference for the hydrolysis of VR-chiral center analogues. This mutant hydrolyzes the two enantiomers of VR 160- and 600-fold faster than wild-type PTE hydrolyzes the SP-enantiomer of VR.

  14. Reactions of VX, HD, and their simulants with NaY and AgY zeolites. Desulfurization of VX on AgY

    Wagner, G.W.; Bartram, P.W.


    The room-temperature reactions of the chemical warfare agents VX (O-ethyl S-2-(diisopropylamino)-ethyl methylphosphonothioate), HD (2,2{prime}-dichloroethyl sulfide, or mustard), and their common simulants, O,S-diethyl phenylphosphonothioate (DEPPT) and 2-chloroethyl phenyl sulfide (CEPS), with NaY and silver-exchanged (AgY) zeolites have been studied using solid-state magic angle spinning NMR. VX hydrolyzes via exclusive cleavage of the P{single{underscore}bond}S bond on both NaY and AgY to yield ethyl methylphosphonate (EMPA). The reaction is significantly faster on AgY than on NaY, suggesting catalysis by silver. On AgY, an intermediate silver salt of EMPA is apparently formed which is slowly converted to ethyl 2-(diisopropylamino)ethyl methylphosphonate (QB, the desulfurized analogue of VX) in about a 78% yield. DEPPT similarly hydrolyzes via P{single{underscore}bond}S cleavage on AgY to yield an apparent silver salt of ethyl phenylphosphonate, which does not undergo further reaction to the desulfurized analogue. No reaction is observed for DEPPT on NaY. HD on AgY forms both vinyl sulfide and the cyclic ether 1,4-thioxane. HD reacts faster on NaY to exclusively form the CH-TG sulfonium ion (HOCH{sub 2}CH{sub 2}SCH{sub 2}CH{sub 2}S{sup +}[CH{sub 2}CH{sub 2}OH]{sub 2}). CEPS also reacts faster on NaY, forming 2-hydroxyethyl phenyl sulfide. On AgY, CEPS does not give the vinyl product, but does yield the ether product PhSCH{sub 2}CH{sub 2}OCH{sub 2}CH{sub 2}SPh. A mechanism is proposed for the silver-catalyzed hydrolysis of VX, the desulfurization of the cleaved thiol, and the formation of QB.

  15. Synthesis and characterization of the open-framework barium bisphosphonate [Ba3(O3PCH2NH2CH2PO3)2(H2O)4].3H2O.

    Bauer, Sebastian; Müller, Helen; Bein, Thomas; Stock, Norbert


    Following the strategy of using polyfunctional phosphonic acids for the synthesis of open-framework metal phosphonates, the phosphonocarboxylic acid (H2O3PCH2)2NCH2C6H4COOH was used in the hydrothermal synthesis of new Ba phosphonates. Its decomposition led to the first open-framework barium phosphonate [Ba3(O3PCH2NH2CH2PO3)2(H2O)4].3H2O. The synthesis was also successfully performed using iminobis(methylphosphonic acid), (H2O3PCH2)2NH, as a starting material, and the synthesis was optimized to obtain as a pure material. The reaction setup as well as the pH are the dominant parameters, and only a diffusion-controlled reaction led to the desired compound. The crystal structure was solved from single-crystal data: monoclinic; C2/c; a=2328.7(2), b=1359.95(7), and c=718.62(6) pm; beta=98.732(10) degrees ; V=2249.5(3)x10(6) pm3; Z=4; R1=0.036; and wR2=0.072 (all data). The structure of [Ba3(O3PCH2NH2CH2PO3)2(H2O)4].3H2O is built up from BaO8 and BaO10 polyhedra forming BaO chains and layers, respectively. These are connected to a three-dimensional metal-oxygen-metal framework with the iminobis(methylphosphonic acid) formally coating the inner walls of the pores. The one-dimensional pores (3.6x4 A) are filled with H2O molecules that can be thermally removed. Thermogravimetric investigations and temperature-dependent X-ray powder diffraction demonstrate the stability of the crystal structure up to 240 degrees C. The uptake of N,N-dimethylformamide and H2O by dehydrated samples is demonstrated. Furthermore, IR, Raman, and 31P magic-angle-spinning NMR data are also presented.

  16. Reaction of nerve agents with phosphate buffer at pH 7.

    Creasy, William R; Fry, Roderick A; McGarvey, David J


    Chemical weapon nerve agents, including isopropyl methylphosphonofluoridate (GB or Sarin), pinacolyl methylphosphonofluoridate (GD or Soman), and S-(2-diisopropylaminoethyl) O-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 (31)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 × 10(-3) M(-1)s(-1)[PO(4)(3-)]. 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 (31)P NMR spectrum. The rate of reaction for GD is slower than GB, with a rate constant of 1.26 × 10(-3) M(-1)s(-1) [PO(4)(3-)]. The rate for VX is considerably slower, with a rate constant of 1.39 × 10(-5) M(-1)s(-1) [PO(4)(3-)], 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 × 10(-3) min(-1) at a concentration of 0.0145 M. The rate of reaction for diisopropyl fluorophosphate is 2.84 × 10(-3) min(-1) 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.

  17. Nonlinear wavelet compression of ion mobility spectra from ion mobility spectrometers mounted in an unmanned aerial vehicle.

    Cao, Libo; Harrington, Peter de B; Harden, Charles S; McHugh, Vincent M; Thomas, Martin A


    Linear and nonlinear wavelet compression of ion mobility spectrometry (IMS) data are compared and evaluated. IMS provides low detection limits and rapid response for many compounds. Nonlinear wavelet compression of ion mobility spectra reduced the data to 4-5% of its original size, while eliminating artifacts in the reconstructed spectra that occur with linear compression, and the root-mean-square reconstruction error was 0.17-0.20% of the maximum intensity of the uncompressed spectra. Furthermore, nonlinear wavelet compression precisely preserves the peak location (i.e., drift time). Small variations in peak location may occur in the reconstructed spectra that were linearly compressed. A method was developed and evaluated for optimizing the compression. The compression method was evaluated with in-flight data recorded from ion mobility spectrometers mounted in an unmanned aerial vehicle (UAV). Plumes of dimethyl methylphosphonate were disseminated for interrogation by the UAV-mounted IMS system. The daublet 8 wavelet filter exhibited the best performance for these evaluations.

  18. Signature-Discovery Approach for Sample Matching of a Nerve-Agent Precursor using Liquid Chromatography–Mass Spectrometry, XCMS, and Chemometrics

    Fraga, Carlos G.; Clowers, Brian H.; Moore, Ronald J.; Zink, Erika M.


    This report demonstrates the use of bioinformatic and chemometric tools on liquid chromatography mass spectrometry (LC-MS) data for the discovery of ultra-trace forensic signatures for sample matching of various stocks of the nerve-agent precursor known as methylphosphonic dichloride (dichlor). The use of the bioinformatic tool known as XCMS was used to comprehensively search and find candidate LC-MS peaks in a known set of dichlor samples. These candidate peaks were down selected to a group of 34 impurity peaks. Hierarchal cluster analysis and factor analysis demonstrated the potential of these 34 impurities peaks for matching samples based on their stock source. Only one pair of dichlor stocks was not differentiated from one another. An acceptable chemometric approach for sample matching was determined to be variance scaling and signal averaging of normalized duplicate impurity profiles prior to classification by k-nearest neighbors. Using this approach, a test set of dichlor samples were all correctly matched to their source stock. The sample preparation and LC-MS method permitted the detection of dichlor impurities presumably in the parts-per-trillion (w/w). The detection of a common impurity in all dichlor stocks that were synthesized over a 14-year period and by different manufacturers was an unexpected discovery. Our described signature-discovery approach should be useful in the development of a forensic capability to help in criminal investigations following chemical attacks.

  19. In Situ Probes of Capture and Decomposition of Chemical Warfare Agent Simulants by Zr-Based Metal Organic Frameworks

    Plonka, Anna M.; Wang, Qi; Gordon, Wesley O.; Balboa, Alex; Troya, Diego; Guo, Weiwei; Sharp, Conor H.; Senanayake, Sanjaya D.; Morris, John R.; Hill, Craig L.; Frenkel, Anatoly I. (BNL); (Virginia Tech); (ECBC); (Emory); (SBU)


    Zr-based metal organic frameworks (MOFs) have been recently shown to be among the fastest catalysts of nerve-agent hydrolysis in solution. We report a detailed study of the adsorption and decomposition of a nerve-agent simulant, dimethyl methylphosphonate (DMMP), on UiO-66, UiO-67, MOF-808, and NU-1000 using synchrotron-based X-ray powder diffraction, X-ray absorption, and infrared spectroscopy, which reveals key aspects of the reaction mechanism. The diffraction measurements indicate that all four MOFs adsorb DMMP (introduced at atmospheric pressures through a flow of helium or air) within the pore space. In addition, the combination of X-ray absorption and infrared spectra suggests direct coordination of DMMP to the Zr6 cores of all MOFs, which ultimately leads to decomposition to phosphonate products. These experimental probes into the mechanism of adsorption and decomposition of chemical warfare agent simulants on Zr-based MOFs open new opportunities in rational design of new and superior decontamination materials.

  20. Highly Sensitive NO2 Detection and DMP Sensing at Room Temperature using Flexible SWNT Thick Film Sensor

    Deepak Kumar


    Full Text Available   Low cost; easy to fabricate and flexible single wall carbon nanotubes thick film resistor (SWNT-TFR for detailed study of NO2 detection is reported. SWNT-TFR was fabricated by vacuum filtration technique on flexible polycarbonate membrane. SWNT-TFR sensor shows selective response to NO2. The response increases from 1.47 per cent to 17.34 per cent with increasing the NO2 concentration from 0.2 ppm to 10 ppm, respectively. Different energy sources, IR, thermal and UV were explored for achieving fast recovery of the SWNT-TFR sensor. The results showed that the gas sensor gives immediate and fast recovery in the presence of UVC light. The calculated detection limit is less than 764 ppt for NO2. We are also presenting sensing of dimethyl methylphosphonate (DMMP as a simulant of sarin. SWNT-TFR gives repeatable response of ~2.7 per cent for 500 ppm of DMMP. This work suggests the possibility to utilise SWNTs-TFR as NO2 sensors for air-quality monitoring. 

  1. Elimination kinetics and molecular reaction mechanisms of cyclosarin (GF) by an oxime substituted β-cyclodextrin derivative in vitro.

    Kranawetvogl, Andreas; Müller, Susanne; Kubik, Stefan; Spruit, Helma; Thiermann, Horst; Worek, Franz; Noort, Daan; Reiter, Georg


    Detoxification mechanisms of the chemical warfare agent cyclosarin (GF) in presence of 6-OxP-CD were investigated in detail in in vitro model systems. Most important finding was the preference of 6-Ox-P-CD to eliminate the more toxic (-)-GF. However, elimination of GF enantiomers was dependent on the 6-OxP-CD:GF ratios showing decreasing stereoselectivity and speed of the reaction with increasing GF concentrations. Formation of covalent mono, bis, tris and tetrakis conjugates ((CHMP)n-6-OxP-CD) and appearance of small molecular fragments (SMF) as possible decomposition products after consumption of 6-OxP-CD could be observed.. Interestingly, the non-toxic metabolite O-cyclohexyl methylphosphonic acid (CHMPA) and covalent mono and bis conjugates of 6-OxP-CD and GF were immediately formed, indicating that GF elimination proceeds along different pathways. These important new insights provide information about the mode of action of 6-Ox-P-CD including the role of the pyridinium aldoxime group on the cyclodextrin ring. They are the basis for further investigations in biological media, which could eventually lead to approval of 6-OxP-CD as a new antidote against nerve agent toxicity.

  2. A molecularly imprinted polymer (MIP)-coated microbeam MEMS sensor for chemical detection

    Holthoff, Ellen L.; Li, Lily; Hiller, Tobias; Turner, Kimberly L.


    Recently, microcantilever-based technology has emerged as a viable sensing platform due to its many advantages such as small size, high sensitivity, and low cost. However, microcantilevers lack the inherent ability to selectively identify hazardous chemicals (e.g., explosives, chemical warfare agents). The key to overcoming this challenge is to functionalize the top surface of the microcantilever with a receptor material (e.g., a polymer coating) so that selective binding between the cantilever and analyte of interest takes place. Molecularly imprinted polymers (MIPs) can be utilized as artificial recognition elements for target chemical analytes of interest. Molecular imprinting involves arranging polymerizable functional monomers around a template molecule followed by polymerization and template removal. The selectivity for the target analyte is based on the spatial orientation of the binding site and covalent or noncovalent interactions between the functional monomer and the analyte. In this work, thin films of sol-gel-derived xerogels molecularly imprinted for TNT and dimethyl methylphosphonate (DMMP), a chemical warfare agent stimulant, have demonstrated selectivity and stability in combination with a fixed-fixed beam microelectromechanical systems (MEMS)-based gas sensor. The sensor was characterized by parametric bifurcation noise-based tracking.

  3. The determination of organophosphonate nerve agent metabolites in human urine by hydrophilic interaction liquid chromatography tandem mass spectrometry.

    Mawhinney, Douglas B; Hamelin, Elizabeth I; Fraser, Rheaclare; Silva, Sathya S; Pavlopoulos, Antonis J; Kobelski, Robert J


    A sensitive, robust isotope dilution LC/MS/MS method is presented for the quantitative analysis of human urine for the alkyl methylphosphonic acid metabolites of five organophosphorus nerve agents (VX, rVX or VR, GB or Sarin, GD or Soman, and GF or Cyclosarin). The selective sample preparation method employs non-bonded silica solid-phase extraction and is partially automated. While working with a mobile phase composition that enhances the electrospray ionization process, the hydrophilic interaction chromatography method results in a 5-min injection-to-injection cycle time, excellent peak shapes and adequate retention (k'=3.1). These factors lead to limits of detection for these metabolites as low as 30 pg/mL in a 1-mL sample of human urine. The quality control data (15 and 75 ng/mL) demonstrate accurate (-0.5 to +3.4%) and precise (coefficients of variation of 2.1-3.6%) quantitative results over the clinically relevant urine concentration range of 1-200 ng/mL for a validation set of 20 standard and quality control sets prepared by five analysts over 54 days. The selectivity of the method is demonstrated for a 100-individual reference range study, as well as the analysis of relevant biological samples. The combined sample preparation and analysis portions of this method have a throughput of 288 samples per day.

  4. Determination of optimal sites of antisense oligonucleotide cleavage within TNFα mRNA

    Lloyd, B. H.; Giles, R. V.; Spiller, D. G.; Grzybowski, J.; Tidd, D. M.; Sibson, D. R.


    Antisense oligonucleotides provide a powerful tool in order to determine the consequences of the reduced expression of a selected target gene and may include target validation and therapeutic applications. Methods of predicting optimum antisense sites are not always effective. We have compared the efficacy of antisense oligonucleotides, which were selected in vitro using random combinatorial oligonucleotide libraries of differing length and complexity, upon putative target sites within TNFα mRNA. The relationship of specific target site accessibility and oligonucleotide efficacy with respect to these parameters proved to be complex. Modification of the length of the recognition sequence of the oligonucleotide library illustrated that independent target sites demonstrated a preference for antisense oligonucleotides of a defined and independent optimal length. The efficacy of antisense oligonucleotide sequences selected in vitro paralleled that observed in phorbol 12-myristate 13-acetate (PMA)-activated U937 cells. The application of methylphosphonate:phosphodiester chimaeric oligonucleotides to U937 cells reduced mRNA levels to up to 19.8% that of the untreated cell population. This approach provides a predictive means to profile any mRNA of known sequence with respect to the identification and optimisation of sites accessible to antisense oligonucleotide activity. PMID:11522838

  5. Decomposition kinetics of dimethyl methylphospate(chemical agent simulant) by supercritical water oxidation

    Bambang VERIANSYAH; Jae-Duck KIM; Youn-Woo LEE


    Supercritical water oxidation (SCWO) has been drawing much attention due to effectively destroy a large variety of high-risk wastes resulting from munitions demilitarization and complex industrial chemical. An important design consideration in the development of supercritical water oxidation is the information of decomposition rate. In this paper, the decomposition rate of dimethyl methylphosphonate(DMMP), which is similar to the nerve agent VX and GB(Sarin) in its structure, was investigated under SCWO conditions. The experiments were performed in an isothermal tubular reactor with a H2O2 as an oxidant. The reaction temperatures were ranged from 398 to 633 ℃ at a fixed pressure of 24 MPa. The conversion of DMMP was monitored by analyzing total organic carbon (TOC) on the liquid effluent samples. It is found that the oxidative decomposition of DMMP proceeded rapidly and a high TOC decomposition up to 99.99% was obtained within 11 s at 555℃. On the basis of data derived from experiments, a global kinetic equation for the decomposition of DMMP was developed. The model predictions agreed well with the experimental data.

  6. Infrared microcalorimetric spectroscopy using uncooled thermal detectors

    Datskos, P.G. [Univ. of Tennessee, Knoxville, TN (United States). Dept. of Physics and Astronomy]|[Oak Ridge National Lab., TN (United States); Rajic, S.; Datskou, I.; Egert, C.M. [Oak Ridge National Lab., TN (United States)


    The authors have investigated a novel infrared microcalorimetric spectroscopy technique that can be used to detect the presence of trace amounts of target molecules. The chemical detection is accomplished by obtaining the infrared photothermal spectra of molecules absorbed on the surface of an uncooled thermal detector. Traditional gravimetric based chemical detectors (surface acoustic waves, quartz crystal microbalances) require highly selective coatings to achieve chemical specificity. In contrast, infrared microcalorimetric based detection requires only moderately specific coatings since the specificity is a consequence of the photothermal spectrum. They have obtained infrared photothermal spectra for trace concentrations of chemical analytes including diisopropyl methylphosphonate (DIMP), 2-mercaptoethanol and trinitrotoluene (TNT) over the wavelength region2.5 to 14.5 {micro}m. They found that in the wavelength region 2.5 to 14.5 {micro}m DIMP exhibits two strong photothermal peaks. The photothermal spectra of 2-mercaptoethanol and TNT exhibit a number of peaks in the wavelength region 2.5 to 14.5 {micro}m and the photothermal peaks for 2-mercaptoethanol are in excellent agreement with infrared absorption peaks present in its IR spectrum. The photothermal response of chemical detectors based on microcalorimetric spectroscopy has been found to vary reproducibly and sensitively as a consequence of adsorption of small number of molecules on a detector surface followed by photon irradiation and can be used for improved chemical characterization.

  7. Genes and gene expression: Localization, damage and control: A multilevel and inter-disciplinary study

    Ts' o, P.O.P.


    The main objectives of this Program Project is to develop strategy and technology for the study of gene structure, organization and function in a multi-disciplinary, highly coordinated manner. In Project I, Molecular Cytology, the establishment of all instrumentation for the computerized microscopic imaging system (CMIS) has been completed with the software in place, including measurement of the third dimension (along the Z-axis). The technique is now at hand to measure single copy DNA in the nucleus, single copy mRNA in the cell, and finally, we are in the process of developing mathematical approaches for the analysis of the relative spatial 3-D relationship among the chromosomes and the individual genes in the interphasal nucleus. Also, we have a sensitive and reliable method for measuring single-stranded DNA breaks which will be useful for the determination of damage to DNA caused by ionizing radiation. In Project II, the mapping of restriction fragments by 2-D enzymatic and electrophoretic analysis has been perfected for application. In Project III, a major finding is that the binding constant and effectiveness of antisense oligonucleotide analogues, Matagen, can be significantly improved by substituting 2{prime}-O-methylribos methylphosphonate backbones for the current 2{prime}-deoxyribomethylphosphonate backbones. 15 refs., 10 figs., 2 tabs.

  8. Glyphosate acetylation as a specific trait of Achromobacter sp. Kg 16 physiology.

    Shushkova, Tatyana V; Vinokurova, Natalya G; Baskunov, Boris P; Zelenkova, Nina F; Sviridov, Alexey V; Ermakova, Inna T; Leontievsky, Alexey A


    The growth parameters of Achromobacter sp. Kg 16 (VKM B-2534 D), such as biomass and maximum specific growth rate, depended only on the source of phosphorus in the medium, but not on the carbon source or the presence of growth factors. With glyphosate as a sole phosphorus source, they were still 40-50 % lower than in media supplemented with orthophosphate or other organophosphonate-methylphosphonic acid. At the first time process of glyphosate acetylation and accumulation of acetylglyphosate in culture medium were revealed in this strain. Acetylglyphosate isolated from cultural liquid was identified by mass spectroscopy; its mass spectrum fully corresponded with that of chemically synthesized acetylglyphosate. Even poorer growth was observed in media with acetylglyphosate: although the strain was able to utilize this compound as a sole source of phosphorus, the maximum biomass was still 58-70 % lower than with glyphosate. The presence of acetylglyphosate in culture medium could also hinder the utilization of glyphosate as a phosphorus source. Therefore, the acetylation of glyphosate may be a specific feature of Achromobacter sp. Kg 16 responsible for its poor growth on this compound.

  9. Phosphorylated multiwalled carbon nanotube-cyclodextrin polymer: synthesis, characterisation and potential application in water purification.

    Mamba, G; Mbianda, X Y; Govender, P P


    Multiwalled carbon nanotubes were synthesised by the nebulised spray pyrolysis method and purified to remove amorphous carbon and fullerenes. The purified multiwalled carbon nanotubes were oxidised using a 3:1 H2SO4/HNO3 mixture to introduce carboxylic groups and to a smaller extent hydroxyl groups on the walls of the carbon nanotubes. Subsequently, the oxidised carbon nanotubes were chlorinated using oxalyl chloride to generate acyl chloride groups through which phosphorylation took place. 4-Aminophenyl methylphosphonate was attached to the multiwalled carbon nanotubes via an amidation reaction. FT-IR and XPS confirmed the presence of PO, PO and PCP functional groups in the phosphorylated carbon nanotubes. Polymerisation of the phosphorylated carbon nanotubes with cyclodextrins was achieved using hexamethylene diisocyanate as a bifunctional linker. Surface morphology of the polymer was investigated by SEM while FT-IR was used to confirm the polymerisation reaction. Moreover, the thermal stability of the polymer was probed using TGA while BET was employed to determine the surface area and pore volume of the polymer. Furthermore, the polymer was tested for the removal of cobalt and 4-chlorophenol from synthetic aqueous solutions of the pollutants. The polymer displayed potential as an adsorbent for both cobalt and 4-chlorophenol.

  10. Facility monitoring of chemical warfare agent simulants in air using an automated, field-deployable, miniature mass spectrometer.

    Smith, Jonell N; Noll, Robert J; Cooks, R Graham


    Vapors of four chemical warfare agent (CWA) stimulants, 2-chloroethyl ethyl sulfide (CEES), diethyl malonate (DEM), dimethyl methylphosphonate (DMMP), and methyl salicylate (MeS), were detected, identified, and quantitated using a fully automated, field-deployable, miniature mass spectrometer. Samples were ionized using a glow discharge electron ionization (GDEI) source, and ions were mass analyzed with a cylindrical ion trap (CIT) mass analyzer. A dual-tube thermal desorption system was used to trap compounds on 50:50 Tenax TA/Carboxen 569 sorbent before their thermal release. The sample concentrations ranged from low parts per billion [ppb] to two parts per million [ppm]. Limits of detection (LODs) ranged from 0.26 to 5.0 ppb. Receiver operating characteristic (ROC) curves are presented for each analyte. A sample of CEES at low ppb concentration was combined separately with two interferents, bleach (saturated vapor) and diesel fuel exhaust (1%), as a way to explore the capability of detecting the simulant in an environmental matrix. Also investigated was a mixture of the four CWA simulants (at concentrations in air ranging from 270 to 380 ppb). Tandem mass (MS/MS) spectral data were used to identify and quantify the individual components. Copyright © 2011 John Wiley & Sons, Ltd.

  11. Detecting recalcitrant organic chemicals in water with microbial fuel cells and artificial neural networks.

    King, Scott T; Sylvander, Marc; Kheperu, Mekhakhem; Racz, LeeAnn; Harper, Willie F


    This study integrates artificial neural network (ANN) processing with microbial fuel cell (MFC)-based biosensing in the detection of three organic pollutants: aldicarb, dimethyl-methylphosphonate (DMMP), and bisphenol-A (BPA). Overall, the use of the ANN proved to be more reliable than direct correlations for the determination of both chemical concentration and type. The ANN output matched the appropriate chemical concentration and type for three different concentrations and throughout a wide range of stepwise tests. Additionally, chemicals dissolved in the acetate-based feed medium (FM) were accurately identified by the ANN even though the acetate masked the pollutants' effects on electrical current. The ANN also accurately revealed the identity of chemical mixtures. This study is the first to incorporate ANN modeling with MFC-based biosensing for the detection and quantification of organic pollutants that are not readily biodegradable. Furthermore, this work provides insight into the flexibility of MFC-based biosensing as it pertains to limits of detection and its applicability to scenarios where mixtures of pollutants and unique solvents are involved. This research effort is expected to serve as a guide for future MFC-based biosensing efforts.

  12. Phosphonate degradation by Spirulina strains: cyanobacterial biofilters for the removal of anticorrosive polyphosphonates from wastewater.

    Forlani, Giuseppe; Prearo, Valentina; Wieczorek, Dorota; Kafarski, Paweł; Lipok, Jacek


    The ability of Spirulina spp. to metabolize the recalcitrant xenobiotic Dequest 2054(®) [hexamethylenediamine-N,N,N',N'-tetrakis(methylphosphonic acid)], a CaSO(4) inhibitor used for boiler treatment and reverse osmosis desalination, was investigated. The compound served as sole source of phosphorus, but not of nitrogen, for cyanobacterial growth. In vivo utilization was followed by (31)P NMR analysis. The disappearance of the polyphosphonate proceeded only with actively dividing cells, and no release of inorganic phosphate was evident. However, no difference was found between P-starved and P-fed cultures. Maximal utilization reached 1.0 ± 0.2 mmoll(-1), corresponding to 0.56 ± 0.11 mmol g(-1) dry biomass, thus residual amounts were still present in the exhausted medium when the compound was supplied at higher initial concentrations. At low substrate levels metabolism rates were lower, suggesting that a concentration-driven uptake may represent a limiting step during the biodegradation process. The compound was not retained by biocolumns made with immobilized cyanobacterial cells, either alive or dead. A lab-scale pilot plant, consisting of a series of sequentially connected vessels containing an actively proliferating algal culture, was built and tested for wastewater treatment. Results showed 50% removal of the polyphosphonate added to an initial concentration of 2.5mM. Although further optimization will be required, data strengthen the possibility of using cyanobacterial strains for bioremediation purposes.

  13. The Different Sensitive Behaviors of a Hydrogen-Bond Acidic Polymer-Coated SAW Sensor for Chemical Warfare Agents and Their Simulants

    Yin Long


    Full Text Available A linear hydrogen-bond acidic (HBA linear functionalized polymer (PLF, was deposited onto a bare surface acoustic wave (SAW device to fabricate a chemical sensor. Real-time responses of the sensor to a series of compounds including sarin (GB, dimethyl methylphosphonate (DMMP, mustard gas (HD, chloroethyl ethyl sulphide (2-CEES, 1,5-dichloropentane (DCP and some organic solvents were studied. The results show that the sensor is highly sensitive to GB and DMMP, and has low sensitivity to HD and DCP, as expected. However, the sensor possesses an unexpected high sensitivity toward 2-CEES. This good sensing performance can’t be solely or mainly attributed to the dipole-dipole interaction since the sensor is not sensitive to some high polarity solvents. We believe the lone pair electrons around the sulphur atom of 2-CEES provide an electron-rich site, which facilitates the formation of hydrogen bonding between PLF and 2-CEES. On the contrary, the electron cloud on the sulphur atom of the HD molecule is offset or depleted by its two neighbouring strong electron-withdrawing groups, hence, hydrogen bonding can hardly be formed.

  14. A simple recovery process for biodegradable plastics accumulated in cyanobacteria treated with ionic liquids.

    Kobayashi, Daigo; Fujita, Kyoko; Nakamura, Nobuhumi; Ohno, Hiroyuki


    Here, we proposed a simple recovery process for poly(3-hydroxybutyrate) (PHB) accumulated in cyanobacteria by using ionic liquids (ILs), which dissolve cyanobacteria but not PHB. First, we investigated the effects of IL polarity on hydrogen-bonding receipt ability (β value) and hydrogen-bonding donating ability (α value) and evaluated the subsequent dissolution of cyanobacteria. We found that ILs having α values higher than approximately 0.4 and β values of approximately 0.9 were suitable for dissolution of cyanobacteria. In particular, 1-ethyl-3-methylimidazolium methylphosphonate ([C2mim][MeO(H)PO2]) was found to dissolve cyanobacteria components, but not PHB. Thus, we verified that PHB produced in cyanobacteria could be separated and recovered by simple filtering after dissolution of cyanobacteria in [C2mim][MeO(H)PO2]. Using this technique, more than 98 % of PHB was obtained on the filter as residues separated from cyanobacteria. Furthermore, [C2mim][MeO(H)PO2] maintained the ability to dissolve cyanobacteria after a simple recycling procedure.

  15. A heterogeneous catalyst, SiO₂-ZnBr₂: An efficient neat access for α-aminophosphonates and antimicrobial activity evaluation



    An efficient, environmentally benign and green method was developed for the synthesis of α-aminophosphonates by one-pot three-component reaction (Kabachnik-Fields reaction) of amine (4-(4-chlorophenoxy) aniline), aldehydes and diethyl phosphite using catalyst, SiO₂-ZnBr₂ under solvent-free conditions. The developed method under conventional conditions was further optimized in microwave and ultrasonication methods. A series of α-aminophosphonates, diethyl (4-(4-chlorophenoxy) phenylamino)(aryl/ heteroaryl) methylphosphonates was synthesized to check the generality. The catalyst, SiO₂-ZnBr₂ afforded good yields of products in all the methods in the range of 85–97% but variation was observed in reaction time. Microwave irradiation method took very less time (4–8 min) as compared with ultrasonication (35–52 min) and conventional (2–3 h) conditions. The major advantages are simple and mild conditions, short reaction times, high yield of the product with purity, use of cheap catalyst and reusability of the catalyst until to three times without significant loss of activity. Antibacterial and antifungal activities were evaluated for the title compounds (50 and 100μg/mL) including minimum inhibitory concentrations. A few of the newly synthesized α-aminophosphonates exhibited promising antimicrobial activity at lower MIC values in the range of 15.0–25.0μg/mL and closer to the standards (5–12μg/mL).

  16. The Different Sensitive Behaviors of a Hydrogen-Bond Acidic Polymer-Coated SAW Sensor for Chemical Warfare Agents and Their Simulants.

    Long, Yin; Wang, Yang; Du, Xiaosong; Cheng, Luhua; Wu, Penglin; Jiang, Yadong


    A linear hydrogen-bond acidic (HBA) linear functionalized polymer (PLF), was deposited onto a bare surface acoustic wave (SAW) device to fabricate a chemical sensor. Real-time responses of the sensor to a series of compounds including sarin (GB), dimethyl methylphosphonate (DMMP), mustard gas (HD), chloroethyl ethyl sulphide (2-CEES), 1,5-dichloropentane (DCP) and some organic solvents were studied. The results show that the sensor is highly sensitive to GB and DMMP, and has low sensitivity to HD and DCP, as expected. However, the sensor possesses an unexpected high sensitivity toward 2-CEES. This good sensing performance can't be solely or mainly attributed to the dipole-dipole interaction since the sensor is not sensitive to some high polarity solvents. We believe the lone pair electrons around the sulphur atom of 2-CEES provide an electron-rich site, which facilitates the formation of hydrogen bonding between PLF and 2-CEES. On the contrary, the electron cloud on the sulphur atom of the HD molecule is offset or depleted by its two neighbouring strong electron-withdrawing groups, hence, hydrogen bonding can hardly be formed.

  17. The Impact of Glyphosate, Its Metabolites and Impurities on Viability, ATP Level and Morphological changes in Human Peripheral Blood Mononuclear Cells

    Kwiatkowska, Marta; Jarosiewicz, Paweł; Michałowicz, Jaromir; Koter-Michalak, Maria; Huras, Bogumiła; Bukowska, Bożena


    The toxicity of herbicides to animals and human is an issue of worldwide concern. The present study has been undertaken to assess toxic effect of widely used pesticide—glyphosate, its metabolites: aminomethylphosphonic acid (AMPA) and methylphosphonic acid and its impurities: N-(phosphonomethyl)iminodiacetic acid (PMIDA), N-methylglyphosate, hydroxymethylphosphonic acid and bis-(phosphonomethyl)amine on human peripheral blood mononuclear cells (PBMCs). We have evaluated the effect of those compounds on viability, ATP level, size (FSC-A parameter) and granulation (SSC-A parameter) of the cells studied. Human peripheral blood mononuclear cells were exposed to different concentrations of glyphosate, its metabolites and impurities (0.01–10 mM) for 4 and 24 h. It was found that investigated compounds caused statistically significant decrease in viability and ATP level of PBMCs. The strongest changes in cell viability and ATP level were observed after 24 h incubation of PBMCs with bis-(phosphonomethyl)amine, and particularly PMIDA. Moreover, all studied compounds changed cell granularity, while PMIDA and bis-(phosphonomethyl)amine altered PBMCs size. It may be concluded that bis-(phosphonomethyl)amine, and PMIDA caused a slightly stronger damage to PBMCs than did glyphosate. Changes in the parameters studied in PBMCs were observed only at high concentrations of the compounds examined, which clearly shows that they may occur in this cell type only as a result of acute poisoning of human organism with these substances. PMID:27280764

  18. Rational Design of a Nile Red/Polymer Composite Film for Fluorescence Sensing of Organophosphonate Vapors using Hydrogen Bond Acidic Polymers

    Levitsky, Igor (Altair Center); Krivoshlykov, Sergei G.(ALTAIR Center, LLC); Grate, Jay W.(BATTELLE (PACIFIC NW LAB))


    The solvatochromic dye Nile Red dispersed in selected hydrogen-bond acidic polymer matrices demonstrated strong fluorescence enhancement at the presence of dimethyl methylphosphonate (DMMP) vapors. Two hydrogen bond acidic polymers were examined as dye matrices, one with fluorinated alcohol groups on a polystyrene backbone (PSFA), and the other with fluorinated bisphenol groups alternating with oligodimethylsiloxane segments (BSP3). The combination of hydrogen-bond acidic polymer (a strong sorbent for DMMP) with the solvatochromic dye led to initial depression of the dye fluorescence and a significant red shift in the absorbance and fluorescence spectra. DMMP sorption changed the dye environment and dramatically altered the fluorescence spectrum and intensity, resulting in a strong fluorescence enhancement. It is proposed that this fluorescence enhancement is due to the competition set up between the dye and the sorbed vapor for polymeric hydrogen bonding sites. The highest responses were obtained with BSP3. DMMP detection has been demonstrated at sub-ppm DMMP concentrations, indicating very low detection limits compared to previous Nile Red/polymer matrix fluorescence vapor sensors. Nile Red/poly(methyl methacrylate) films prepared for comparisons exhibited substantially lower response to DMMP. Rational selection of polymers providing high sorption for DMMP and competition for hydrogen-bonding interactions with Nile Red yielded fluorescent films with high sensitivity.

  19. The coupling of direct analysis in real time ionization to Fourier transform ion cyclotron resonance mass spectrometry for ultrahigh-resolution mass analysis.

    Rummel, Julia L; McKenna, Amy M; Marshall, Alan G; Eyler, John R; Powell, David H


    Direct Analysis in Real Time (DART) is an ambient ionization technique for mass spectrometry that provides rapid and sensitive analyses with little or no sample preparation. DART has been reported primarily for mass analyzers of low to moderate resolving power such as quadrupole ion traps and time-of-flight (TOF) mass spectrometers. In the current work, a custom-built DART source has been successfully coupled to two different Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers for the first time. Comparison of spectra of the isobaric compounds, diisopropyl methylphosphonate and theophylline, acquired by 4.7 T FT-ICR MS and TOF MS, demonstrates that the TOF resolving power can be insufficient for compositionally complex samples. 9.4 T FT-ICR MS yielded the highest mass resolving power yet reported with DART ionization for 1,2-benzanthracene and 9,10-diphenylanthracene. Polycyclic aromatic hydrocarbons exhibit a spatial dependence in ionization mechanisms between the DART source and the mass spectrometer. The feasibility of analyzing a variety of samples was established with the introduction and analysis of food products and crude oil samples. DART FT-ICR MS provides complex sample analysis that is rapid, highly selective and information-rich, but limited to relatively low-mass analytes.

  20. A comparative analysis of pharmacokinetics properties of diagnostic bone-seeking radiopharmaceuticals on the basis of phosphonic acids and technetium-99m

    Tishchenko, V. K.; Petriev, V. M.; Smoryzanova, O. A.; Zavestovskaya, I. N.


    This work is devoted to comparative research of pharmacokinetics properties of four bone-seeking radiopharmaceuticals (RPP) on the basis of bi- tetra- and penta-phosphonic acids. Biodistribution studies were performed in intact rats after intravenous injections of 99mTc-hydroxyethylidenediphosphonic acid (99mTc-HEDP), 99mTc-oxabiphor (99mTc-OXB), 99mTc-ethylenediaminetetramethylenephosphonic acid (99mTc-EDTMP) or 99mTc-diethylenetriaminopentakis(methylphosphonic acid) (99mTc-PPA). In the structure of the HEDP contains two phosphonic groups, OENTMP and EDTMP – four phosphonic groups, PPA – five phosphonic groups. Radiochemical yield of labeled 99mTc HEDP, OENTMP, EDTMP, PPA is not less than 95%, the radiochemical impurities does not exceed 5%. The investigated compounds have high stability in vivo and selective accumulation in osseous tissue. The highest concentrations of labeled compounds is reached in 3–24 hours after their intravenous injections. The investigated compounds are rapidly excreted from blood and soft organs and tissues mainly through the urinary routes. So present study has showed that these RPP have properties, which making them promising candidates as a diagnostic pharmaceuticals of bone metastases.

  1. FY05 FM Dial Summary Report

    Harper, Warren W.; Strasburg, Jana D.; Golovich, Elizabeth C.; Thompson, Jason S.; Stewart, Timothy L.; Batdorf, Michael T.


    Pacific Northwest National Laboratory's Infrared Sensors team is focused on developing methods for standoff detection of nuclear proliferation. In FY05, PNNL continued the development of the FM DIAL (frequency-modulated differential absorption LIDAR) experiment. Additional improvements to the FM DIAL trailer provided greater stability during field campaigns which made it easier to explore new locations for field campaigns. In addition to the Hanford Townsite, successful experiments were conducted at the Marine Science Laboratory in Sequim, WA and the Nevada Test Site located outside Las Vegas, NV. The range of chemicals that can be detected by FM DIAL has also increased. Prior to FY05, distributed feedback quantum cascade lasers (DFB-QCL) were used in the FM DIAL experiments. With these lasers, only simple chemicals with narrow (1-2 cm-1) absorption spectra, such as CO2 and N2O, could be detected. Fabry-Perot (FP) QC lasers have much broader spectra (20-40 cm-1) which allows for the detection of larger chemicals and a wider array of chemicals that can be detected. A FP-QCL has been characterized and used during initial studies detecting DMMP (dimethyl methylphosphonate).

  2. Coacervate Core Micelles for the Dispersion and Stabilization of Organophosphate Hydrolase in Organic Solvents

    Mills, Carolyn; Obermeyer, Allie; Dong, Xuehui; Olsen, Bradley D.

    Bulk organophosphate (OP) nerve agents are difficult to decontaminate on site and dangerous to transport. The organophosphate hydrolase (OPH) enzyme is an efficient catalyst for hydrolyzing, and thus decontaminating, these compounds, but suffers from poor stability in the hydrophobic bulk OP environment. Here, we exploit the complex coacervation phase separation phenomenon to form complex coacervate core micelles (C3Ms) that can protect this OPH enzyme under these conditions. Stable C3Ms form when mixing a charged-neutral block copolymer methyl-quaternized poly(4-vinylpyridine)-block-poly(oligo(ethylene glycol) methacrylate) (Qp4vp- b-POEGMA), a homopolymer poly(acrylic acid) (PAA), and OPH under a certain conditions. The C3Ms are then transferred into two organic solvents, ethanol and dimethyl methylphosphonate (DMMP), which is a good simulant for the physical properties of the OP compounds. The C3Ms retain their nanostructures in the organic solvents. The activity test of OPH indicates that the C3Ms successfully protect OPH activity in organic solvents.

  3. Repeated exposure to sublethal doses of the organophosphorus compound VX activates BDNF expression in mouse brain.

    Pizarro, Jose M; Chang, Wenling E; Bah, Mariama J; Wright, Linnzi K M; Saviolakis, George A; Alagappan, Arun; Robison, Christopher L; Shah, Jinesh D; Meyerhoff, James L; Cerasoli, Douglas M; Midboe, Eric G; Lumley, Lucille A


    The highly toxic organophosphorus compound VX [O-ethyl S-[2-(diisopropylamino)ethyl]methylphosphonate] is an irreversible inhibitor of the enzyme acetylcholinesterase (AChE). Prolonged inhibition of AChE increases endogenous levels of acetylcholine and is toxic at nerve synapses and neuromuscular junctions. We hypothesized that repeated exposure to sublethal doses of VX would affect genes associated with cell survival, neuronal plasticity, and neuronal remodeling, including brain-derived neurotrophic factor (BDNF). We examined the time course of BDNF expression in C57BL/6 mouse brain following repeated exposure (1/day × 5 days/week × 2 weeks) to sublethal doses of VX (0.2 LD(50) and 0.4 LD(50)). BDNF messenger RNA expression was significantly (p VX exposure. BDNF protein expression, however, was only increased in the CA3 region of the hippocampus. Whether increased BDNF in response to sublethal doses of VX exposure is an adaptive response to prevent cellular damage or a precursor to impending brain damage remains to be determined. If elevated BDNF is an adaptive response, exogenous BDNF may be a potential therapeutic target to reduce the toxic effects of nerve agent exposure.

  4. Role of the P-F bond in fluoride-promoted aqueous VX hydrolysis: an experimental and theoretical study.

    Marciano, Daniele; Columbus, Ishay; Elias, Shlomi; Goldvaser, Michael; Shoshanim, Ofir; Ashkenazi, Nissan; Zafrani, Yossi


    Following our ongoing studies on the reactivity of the fluoride ion toward organophosphorus compounds, we established that the extremely toxic and environmentally persistent chemical warfare agent VX (O-ethyl S-2-(diisopropylamino)ethyl methylphosphonothioate) is exclusively and rapidly degraded to the nontoxic product EMPA (ethyl methylphosphonic acid) even in dilute aqueous solutions of fluoride. The unique role of the P-F bond formation in the reaction mechanism was explored using both experimental and computational mechanistic studies. In most cases, the "G-analogue" (O-ethyl methylphosphonofluoridate, Et-G) was observed as an intermediate. Noteworthy and of practical importance is the fact that the toxic side product desethyl-VX, which is formed in substantial quantities during the slow degradation of VX in unbuffered water, is completely avoided in the presence of fluoride. A computational study on a VX-model, O,S-diethyl methylphosphonothioate (1), clarifies the distinctive tendency of aqueous fluoride ions to react with such organophosphorus compounds. The facility of the degradation process even in dilute fluoride solutions is due to the increased reactivity of fluoride, which is caused by the significant low activation barrier for the P-F bond formation. In addition, the unique nucleophilicity of fluoride versus hydroxide toward VX, in contrast to their relative basicity, is discussed. Although the reaction outcomes were similar, much slower reaction rates were observed experimentally for the VX-model (1) in comparison to VX.

  5. α-(Substituted-phenoxyacetoxy)-α-heterocyclylmethylphosphonates: synthesis, herbicidal activity, inhibition on pyruvate dehydrogenase complex (PDHc), and application as postemergent herbicide against broadleaf weeds.

    He, Hong-Wu; Peng, Hao; Wang, Tao; Wang, Chubei; Yuan, Jun-Lin; Chen, Ting; He, Junbo; Tan, Xiaosong


    Pyruvate dehydrogenase complex (PDHc) is the site of action of a new class of herbicides. On the basis of the previous work for O,O'-dimethyl α-(substituted-phenoxyacetoxy)alkylphosphonates (I), further synthetic modifications were made by introducing a fural and a thienyl group to structure I. A series of α-(substituted-phenoxyacetoxy)-α-heterocyclylmethylphosphonate derivatives (II) were synthesized as potential inhibitors of PDHc. The postemergent activity of the title compounds II was evaluated in greenhouse experiments. The in vitro efficacy of II against PDHc was also examined. Compounds II with fural as R(3) and 2,4-dichloro as X and Y showed significant herbicidal activity and effective inhibition against PDHc from plants. O,O'-Dimethyl α-(2,4-dichlorophenoxyacetoxy)-α-(furan-2-yl)methylphosphonate II-17 had higher inhibitory potency against PDHc from Pisum sativum than against PDHc from Oryza sativa in vitro and was most effective against broadleaf weeds at 50 and 300 ai g/ha. II-17 was safe for maize and rice even at the dose of 900-1200 ai g/ha. Field trials at different regions in China showed that II-17 (HWS) could control a broad spectrum of broad-leaved and sedge weeds at the rate of 225-375 ai g/ha for postemergent applications in maize fields. II-17 (HWS) displayed potential utility as a selective herbicide.

  6. An isomer-specific high-energy collision-induced dissociation MS/MS database for forensic applications: a proof-of-concept on chemical warfare agent markers.

    Subramaniam, Raja; Östin, Anders; Nygren, Yvonne; Juhlin, Lars; Nilsson, Calle; Åstot, Crister


    Spectra database search has become the most popular technique for the identification of unknown chemicals, minimizing the need for authentic reference chemicals. In the present study, an isomer-specific high-energy collision-induced dissociation (CID) MS/MS spectra database of 12 isomeric O-hexyl methylphosphonic acids (degradation markers of nerve agents) was created. Phosphonate anions were produced by the electrospray ionization of phosphonic acids or negative-ion chemical ionization of their fluorinated derivatives and were analysed in a hybrid magnetic-sector-time-of-flight tandem mass spectrometer. A centre-of-mass energy (E(com)) of 65 eV led to an optimal sequential carbon-carbon bond breakage, which was interpreted in terms of charge remote fragmentation. The proposed mechanism is discussed in comparison with the routinely used low-energy CID MS/MS. Even-mass (odd-electron) charge remote fragmentation ion series were diagnostic of the O-alkyl chain structure and can be used to interpret unknown spectra. Together with the odd-mass ion series, they formed highly reproducible, isomer-specific spectra that gave significantly higher database matches and probability factors (by 1.5 times) than did the EI MS spectra of the trimethylsilyl derivatives of the same isomers. In addition, ionization by negative-ion chemical ionization and electrospray ionization resulted in similar spectra, which further highlights the general potential of the high-energy CID MS/MS technique.

  7. Effect of DMMP on the pyrolysis products of polyurethane foam materials in the gaseous phase

    Liu, W.; Li, F.; Ge, X. G.; Zhang, Z. J.; He, J.; Gao, N.


    Dimethyl methylphosphonate (DMMP) has been used as a flame retardant containing phosphorus to decrease the flammability of the polyurethane foam material (PUF). Flame retardancy and thermal degradation of PUF samples have been investigated by the LOI tests and thermal analysis. The results show that LOI values of all PUF/DMMP samples are higher than that of the neat PUF sample and the LOI value of the samples increases with both DMMP concentration and the %P value. Thermal analysis indicates that flame retardant PUF shows a dominant condensed flame retardant activity during combustion. Thermogravimetric analysis-infrared spectrometry (TG-FTIR) has been used to study the influence of DMMP on the pyrolysis products in the gaseous phase during the thermal degradation of the PUF sample. Fourier transform infrared spectrometry (FTIR) spectra of the PUF sample at the maximum evolution rates and the generated trends of water and the products containing -NCO have been examined to obtain more information about the pyrolysis product evolutions of the samples at high temperature. These results reveal that although DMMP could improve the thermal stability of PUF samples through the formation of the residual char layer between fire and the decomposed materials, the influence of DMMP on the gaseous phase can be also observed during the thermal degradation process of materials.

  8. Y-Hydroxyphosphonate inducing single-chain antibodies capable of catalyzing soman hydrolysis

    王字玲; 荣康泰; 杨日芳; 恽榴红


    A γ-hydroxyphosphonate P6 (O1-methyl-O2-(1, 2, 2-trimethylpropyl)-2-hydroxy-5-nitro-phenyl methylphosphonic acid) which is proposed to be an analog of the transition state in hydrolysis of soman was synthesized. Artificial antigens were obtained by conjugating P6 to the carrier proteins BSA (bovine serum albumin) and LPH (Limulus polyphenus hemocyanin). Mice were immunized with P6-LPH and recombinant single-chain antibody phage display library was constructed. After 4 rounds of panning against P6-BSA and competitive inhibition enzyme immunoassay, more than 70 strains of phage antibodies capable of binding soman were obtained and 11 of them can accelerate the hydrolysis reaction of soman. One of them (EP6) was studied further. Soluble single-chain antibody was prepared and purification was performed by gel filtration and ion exchange chromatography. The kinetic experiment was carried out showing that the turnover number kcatt= 198 min-1 and the rate enhancement kcatkuncat = 122 419. When 0.16 mg · mL-1

  9. A bio-enabled maximally mild layer-by-layer Kapton surface modification approach for the fabrication of all-inkjet-printed flexible electronic devices

    Fang, Yunnan; Hester, Jimmy G. D.; Su, Wenjing; Chow, Justin H.; Sitaraman, Suresh K.; Tentzeris, Manos M.


    A bio-enabled, environmentally-friendly, and maximally mild layer-by-layer approach has been developed to surface modify inherently hydrophobic Kapton HN substrates to allow for great printability of both water- and organic solvent-based inks thus facilitating the full-inkjet-printing of flexible electronic devices. Different from the traditional Kapton surface modification approaches which are structure-compromising and use harsh conditions to target, and oxidize and/or remove part of, the surface polyimide of Kapton, the present Kapton surface modification approach targeted the surface electric charges borne by its additive particles, and was not only the first to utilize environmentally-friendly clinical biomolecules to build up a thin film of protamine-heparin complex on Kapton, but also the first to be conducted under minimally destructive and maximally mild conditions. Besides, for electrically charged ink particles, the present surface modification method can enhance the uniformity of the inkjet-printed films by reducing the “coffee ring effect”. As a proof-of-concept demonstration, reduced graphene oxide-based gas sensors, which were flexible, ultra-lightweight, and miniature-sized, were fully-inkjet-printed on surface modified Kapton HN films and tested for their sensitivity to dimethyl methylphosphonate (a nerve agent simulant). Such fabricated sensors survived a Scotch-tape peel test and were found insensitive to repeated bending to a small 0.5 cm radius.

  10. Preliminary Effects of Real-World Factors on the Recovery and Exploitation of Forensic Impurity Profiles of a Nerve-Agent Simulant from Office Media

    Fraga, Carlos G.; Sego, Landon H.; Hoggard, Jamin C.; Perez Acosta, Gabriel A.; Viglino, Emilie A.; Wahl, Jon H.; Synovec, Robert E.


    Dimethyl methylphosphonate (DMMP) was used as a chemical threat agent (CTA) simulant for a first look at the effects of real-world factors on the recovery and exploitation of a CTA’s impurity profile for source matching. Four stocks of DMMP having different impurity profiles were disseminated as aerosols onto cotton, painted wall board, and nylon coupons according to a thorough experimental design. The DMMP-exposed coupons were then solvent extracted and analyzed for DMMP impurities by comprehensive 2-D gas chromatography/mass spectrometry (GC×GC/MS). The similarities between the coupon DMMP impurity profiles and the known (reference) DMMP profiles were measured by dot products of the coupon profiles and known profiles and by score values obtained from principal component analysis. One stock, with a high impurity-profile selectivity value of 0.9 out of 1, had 100% of its respective coupons correctly classified and no false positives from other coupons. Coupons from the other three stocks with low selectivity values (0.0073, 0.012, and 0.018) could not be sufficiently distinguished from one another for reliable matching to their respective stocks. The results from this work support that: (1) extraction solvents, if not appropriately selected, can have some of the same impurities present in a CTA reducing a CTA’s useable impurity profile, (2) low selectivity among a CTA’s known impurity profiles will likely make definitive source matching impossible in some real-world conditions, (3) no detrimental chemical-matrix interference was encountered during the analysis of actual office media, (4) a short elapsed time between release and sample storage is advantageous for the recovery of the impurity profile because it minimizes volatilization of forensic impurities, and (5) forensic impurity profiles weighted towards higher volatility impurities are more likely to be altered by volatilization following CTA exposure.

  11. Theoretical Investigation of Mechanisms for the Gas-Phase Unimolecular Decomposition of DMMP

    Yang, Li; Shroll, Robert M.; Zhang, Jiaxu; Lourderaj, U.; Hase, William L.


    All species involved in the multichannel decomposition of gas-phase dimethyl methylphosphonate (DMMP) were investigated by electronic structure calculations. Geometries for stationary structures along the reaction paths, were fully optimized with the MP2 method and the B3LYP and MPW1K DFT functionals, and the 6-31G*, 6-31++G**, and aug-cc-pVDZ basis sets. The geometries determined by the B3LYP and MPW1K functionals are in very good agreement with the MP2 values. Increasing the basis set size from 6-31G* to aug-cc-pVDZ does not significantly alter this result. Single point energy calculations were carried out with highly accurate but computationally more expensive CBS-QB3 theory. DMMP has three conformers, which lead to the four primary product channels, (O)P(CH2)(OCH3) + CH3OH, (O)P(CH3) (OCH3)(OH) + CH2, c-(O)P(CH3)OCH2 + CH3OH, and (O)P(CH3)(OCH3)(OCH) + H2. The first channel has the lowest energy barrier and is expected to be the most important pathway. It occurs via C-H and P-O bond cleavages accompanied by O-H bond formation. The other three channels have higher and similar energy barriers, and are expected to have smaller and similar rates. The product (O)P(CH3)(OCH3)(OCH) undergoes a secondary decomposition to form (OH)P(CH3)(OCH3) + CO.

  12. 蓖麻油多元醇在聚氨酯阻燃硬泡中的应用研究%Application of Castor Oil Polyol in the Flame-Retardant Rigid Polyurethane Foam

    冯月兰; 李其峰; 王军威; 亢茂青; 曹月领; 王心葵


    Castor oil polyol (COP) was prepared by the transesterification of castor oil with glycerin, and applied for the manufacture of inflaming retarding rigid polyurethane foam ( RPUF). The effect of flame-retardants type and content, COP dosage on the overall performance of RPUF was investigated. The results showed that COP affected the limiting oxygen index of RPUF slightly, except that the RPUF could shrink when the COP content exceeded 50%. Among the introduced flame-retardants, dimethyl methylphosphonate ( DMMP) exhibited highest flame resistance for RPUF. The further investigation confirmed that adding DMMP of about 20% ~ 30% of totel polyols weight should be more favorable for keeping overall performance of RPUF.%通过蓖麻油与甘油进行酯交换反应制备蓖麻油多元醇,并应用于聚氨酯阻燃硬泡的制备,研究了阻燃剂类型、添加量及蓖麻油多元醇的添加量对聚氨酯硬质泡沫(RPUF)综合性能的影响.结果表明,蓖麻油多元醇的添加量对阻燃RPUF氧指数影响不大,只是添加量大于50%时会导致泡沫收缩;添加不同阻燃剂后发现甲基磷酸二甲酯(DMMP)的阻燃效果好,DMMP合适用量为多元醇组分的20% ~ 30%.

  13. Impurity Profiling of a Chemical Weapon Precursor for Possible Forensic Signatures by Comprehensive Two-Dimensional Gas Chromatography/Mass Spectrometry and Chemometrics

    Hoggard, Jamin C.; Wahl, Jon H.; Synovec, Robert E.; Mong, Gary M.; Fraga, Carlos G.


    In this work we present the feasibility of using analytical chemical and chemometric methodologies to reveal and exploit the organic impurity profiles from commercial dimethyl methylphosphonate (DMMP) samples to illustrate the type of forensic information that may be obtained from chemical-attack evidence. Using DMMP as a model compound for a toxicant that may be used in a chemical attack, we used comprehensive two-dimensional gas chromatography mass spectrometric detection (GC × GC-TOFMS) to detect and identify trace organic impurities in six samples of commercially acquired DMMP. The GC x GC-TOFMS data were analyzed to produce impurity profiles for all six DMMP samples using 29 analyte impurities. The use of PARAFAC for the mathematical resolution of overlap GC x GC peaks ensured clean spectra for the identification of many of the detected analytes by spectral library matching. The use of statistical pairwise comparison revealed that there were trace impurities that were quantitatively similar and different among five of the six DMMP samples. Two of the DMMP samples were revealed to have identical impurity profiles by this approach. The use of nonnegative matrix factorization proved that there were five distinct DMMP sample types as illustrated by the clustering of the multiple DMMP analyses into 5 distinct clusters in the scores plots. The two indistinguishable DMMP samples were confirmed by their chemical supplier to be from the same bulk source. Sample information from the other chemical suppliers supported that the other five DMMP samples were likely from different bulk sources. These results demonstrate that the matching of synthesized products from the same source is possible using impurity profiling. In addition, the identified impurities common to all six DMMP samples provide strong evidence that basic route information can be obtained from impurity profiles. In addition, impurities that may be unique to the sole bulk manufacturer of DMMP were found in

  14. Paraoxonase activity against nerve gases measured by capillary electrophoresis and characterization of human serum paraoxonase (PON1) polymorphism in the coding region (Q192R).

    Kanamori-Kataoka, Mieko; Seto, Yasuo


    An analytical method for determining paraoxonase activity against sarin, soman and VX was established. We used capillary electrophoresis to measure directly the hydrolysis products: alkyl methylphosphonates. After enzymatic reaction of human serum paraoxonase (PON1) with nerve gas, substrate was removed with dichloromethane, and alkyl methylphoshphonates were quantified by capillary electrophoresis of reversed osmotic flow using cationic detergent and sorbic acid. This method was applied to the characterization of human serum PON1 polymorphism for nerve gas hydrolytic activity in the coding region (Q192R). PON1-192 and PON1-55 genotypes were determined by their gel electrophoretic fragmentation pattern with restriction enzymes after polymerase chain reaction (PCR) of blood leukocyte genomic DNA. Frequencies of genotypes among 63 members of our institutes with PON1-192 and PON1-55 were 9.5% ((192)QQ), 30.1% ((192)QR) and 44.4% ((192)RR), and 82.5% ((55)LL), 17.5% ((55)LM) and 0% ((55)MM), respectively. (192)Q and (192)R enzymes were purified from the respective genotype human plasma, using blue agarose affinity chromatography and diethyl amino ethane (DEAE) anion exchange chromatography. V(max) and K(m) were measured using Lineweaver-Burk plots for hydrolytic activities against sarin, soman and VX at pH 7.4 and 25 degrees C. For sarin and soman, the V(max) for (192)Q PON1 were 3.5- and 1.5-fold higher than those for (192)R PON1; and k(cat)/K(m) for (192)Q PON1 were 1.3- and 2.8-fold higher than those for (192)R PON1. For VX, there was little difference in V(max) and k(cat)/K(m) between (192)Q and (192)R PON1, and VX hydrolyzing activity was significantly lower than those for sarin and soman. PON1 hydrolyzed sarin and soman more effectively than paraoxon.

  15. Effectiveness and reaction networks of H2O2 vapor with NH3 gas for decontamination of the toxic warfare nerve agent, VX on a solid surface.

    Gon Ryu, Sam; Wan Lee, Hae


    The nerve agent, O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) must be promptly eliminated following its release into the environment because it is extremely toxic, can cause death within a few minutes after exposure, acts through direct skin contact as well as inhalation, and persists in the environment for several weeks after release. A mixture of hydrogen peroxide vapor and ammonia gas was examined as a decontaminant for the removal of VX on solid surfaces at ambient temperature, and the reaction products were analyzed by gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectrometry (NMR). All the VX on glass wool filter disks was found to be eliminated after 2 h of exposure to the decontaminant mixtures, and the primary decomposition product was determined to be non-toxic ethyl methylphosphonic acid (EMPA); no toxic S-[2-(diisopropylamino)ethyl] methylphosphonothioic acid (EA-2192), which is usually produced in traditional basic hydrolysis systems, was found to be formed. However, other by-products, such as toxic O-ethyl S-vinyl methylphosphonothioate and (2-diisopropylaminoethyl) vinyl disulfide, were detected up to 150 min of exposure to the decontaminant mixture; these by-products disappeared after 3 h. The two detected vinyl byproducts were identified first in this study with the decontamination system of liquid VX on solid surfaces using a mixture of hydrogen peroxide vapor and ammonia gas. The detailed decontamination reaction networks of VX on solid surfaces produced by the mixture of hydrogen peroxide vapor and ammonia gas were suggested based on the reaction products. These findings suggest that the mixture of hydrogen peroxide vapor and ammonia gas investigated in this study is an efficient decontaminant mixture for the removal of VX on solid surfaces at ambient temperature despite the formation of a toxic by-product in the reaction process.

  16. Evaluating and modeling the effects of surface sampling factors on the recovery of organic chemical attribution signatures using the accelerated diffusion sampler and solvent extraction

    Mo, Kai-For; Heredia-Langner, Alejandro; Fraga, Carlos G.


    In this study, an experimental design matrix was created and executed in order to test the effects of various real-world factors on the ability of the (1) accelerated diffusion sampler with solid phase micro-extraction (ADS-SPME) and (2) solvent extraction to capture organic chemical attribution signatures (CAS) from dimethyl methylphosphonate (DMMP) spiked onto painted wall board (PWB) surfaces. The DMMP CAS organic impurities sampled by ADS-SPME and solvent extraction were analyzed by gas chromatography/mass spectrometry (GC/MS). The number of detected DMMP CAS impurities and their respective GC/MS peak areas were determined as a function of DMMP stock, DMMP spiked volume, exposure time, SPME sampling time, and ADS headspace pressure. Based on the statistical analysis of experimental results, several general conclusions are made: (1) ADS-SPME with vacuum (i.e., reduced pressure) increased the amount of detected CAS impurity, as measured by GC/MS peak area, by a factor of 1.7 to 1.9 for PWB under certain experimental conditions, (2) the amount of detected CAS impurity was most influenced by spiked volume, stock, and ADS headspace pressure, (3) the ADS had no measurable effect on the number of detected DMMP impurities, that is, the ADS (with and without reduced pressure) had no practical effect on the DMMP impurity profile collected from spiked PWB, and (4) solvent extraction out performed ADS-SPME in terms of consistently capturing all or most of the targeted DMMP impurities from spiked PWB.

  17. Evaluating and modeling the effects of surface sampling factors on the recovery of organic chemical attribution signatures using the accelerated diffusion sampler and solvent extraction.

    Mo, Kai-For; Heredia-Langner, Alejandro; Fraga, Carlos G


    In this study, an experimental design matrix was created and executed to test the effects of various real-world factors on the ability of (1) the accelerated diffusion sampler with solid phase micro-extraction (ADS-SPME) and (2) solvent extraction to capture organic chemical attribution signatures (CAS) from dimethyl methylphosphonate (DMMP) spiked onto painted wall board (PWB) surfaces. The DMMP CAS organic impurities sampled by ADS-SPME and solvent extraction were analyzed by gas chromatography/mass spectrometry (GC/MS). The number of detected DMMP CAS impurities and their respective GC/MS peak areas were determined as a function of DMMP stock, DMMP spiked volume, exposure time, SPME sampling time, and ADS headspace pressure. Based on the statistical analysis of experimental results, several general conclusions are made: (1) the amount of CAS impurity detected using ADS-SPME and GC/MS was most influenced by spiked volume, stock, and ADS headspace pressure, (2) reduced ADS headspace pressure increased the amount of detected CAS impurity, as measured by GC/MS peak area, by up to a factor of 1.7-1.9 compared to ADS at ambient headspace pressure, (3) the ADS had no measurable effect on the number of detected DMMP impurities, that is, ADS (with and without reduced pressure) had no practical effect on the DMMP impurity profile collected from spiked PWB, and (4) solvent extraction out performed ADS-SPME in terms of consistently capturing all or most of the targeted DMMP impurities from spiked PWB.

  18. Rapid Synthesis and Antiviral Activity of (Quinazolin-4-YlaminoMethyl-Phosphonates Through Microwave Irradiation

    Baoan Song


    Full Text Available This study describes the simple synthesis of new (quinazolin-4-ylamino methylphosphonates via microwave irradiation. Substituted-2-aminobenzonitrile reacted with 1,1-dimethoxy-N,N-dimethylmethanamine at a reflux condition to obtain N'-(substituted-2-cyanophenyl-N,N-dimethylformamidine (1. The subsequent reaction of this intermediate product with α-aminophosphonate (2 in a solution containing glacial acetic acid in 2-propanol through microwave irradiation resulted in the formation of (quinazolin-4-ylaminomethyl-phosphonate derivatives 3a to 3x, which were unequivocally characterized by the spectral data and elemental analysis. The influence of the reaction conditions on the yield of 3a was investigated to optimize the synthetic conditions. The relative optimal conditions for the synthesis of 3a include a 1:1 molar ratio of N’-(2-cyanophenyl-N,N-dimethylformamidine to diethyl amino(phenylmethylphosphonate and a 4:1 volume ratio of isopropanol to HOAc in the solvent mixture, at a reaction temperature of 150 °C, with a microwave power of 100 W and a corresponding pressure of 150 psi for 20 min in the microwave synthesizer. The yield of 3a was approximately 79%, whereas those of 3b to 3x were approximately 77% to 86%. Some of the synthesized compounds displayed weak to good anti-Tobacco mosaic virus (TMV activity.

  19. Oleate-based hydrothermal preparation of CoFe{sub 2}O{sub 4} nanoparticles, and their magnetic properties with respect to particle size and surface coating

    Repko, Anton, E-mail: [Department of Inorganic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 2030/8, 128 43 Prague 2 (Czech Republic); Vejpravová, Jana, E-mail: [Department of Magnetic Nanosystems, Institute of Physics AS CR, v.v.i., Na Slovance 2, 182 21 Prague 8 (Czech Republic); Vacková, Taťana [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6 (Czech Republic); Zákutná, Dominika [Department of Inorganic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 2030/8, 128 43 Prague 2 (Czech Republic); Nižňanský, Daniel, E-mail: [Department of Inorganic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 2030/8, 128 43 Prague 2 (Czech Republic)


    We present a facile and high-yield synthesis of cobalt ferrite nanoparticles by hydrothermal hydrolysis of Co–Fe oleate in the presence of pentanol/octanol/toluene and water at 180 or 220 °C. The particle size (6–10 nm) was controlled by the composition of the organic solvent and temperature. Magnetic properties were then investigated with respect to the particle size and surface modification with citric acid or titanium dioxide (leading to hydrophilic particles). The as-prepared hydrophobic nanoparticles (coated by oleic acid) had a minimum inter-particle distance of 2.5 nm. Their apparent blocking temperature (estimated as a maximum of the zero-field-cooled magnetization) was 180 K, 280 K and 330 K for the particles with size of 6, 9 and 10.5 nm, respectively. Replacement of oleic acid on the surface by citric acid decreased inter-particle distance to less than 1 nm, and increased blocking temperature by ca. 10 K. On the other hand, coating with titanium dioxide, supported by nitrilotri(methylphosphonic acid), caused increase of the particle spacing, and lowering of the blocking temperature by ca. 20 K. The CoFe{sub 2}O{sub 4}@TiO{sub 2} nanoparticles were sufficiently stable in water, methanol and ethanol. The particles were also investigated by Mössbauer spectroscopy and alternating-current (AC) susceptibility measurements, and their analysis with Vögel–Fulcher and power law. Effect of different particle coating and dipolar interactions on the magnetic properties is discussed. - Highlights: • CoFe{sub 2}O{sub 4} nanoparticles were prepared by facile hydrothermal method from Co–Fe oleate. • Blocking temperature (T{sub B}) is 180–330 K for 6–10.5 nm oleate-coated particles. • The apparent T{sub B} changes with oleic acid, citrate or TiO{sub 2} coating.

  20. γ-Hydroxyphosphonate inducing single-chain antibodies capable of catalyzing soman hydrolysis


    A γ-hydroxyphosphonate P6 (O1-methyl-O2-(1, 2, 2-trimethylpropyl)-2-hydroxy-5-nitrophenyl methylphosphonic acid) which is proposed to be an analog of the transition state in hydrolysis of soman was synthesized. Artificial antigens were obtained by conjugating P6 to the carrier proteins BSA (bovine serum albumin) and LPH (Limulus polyphenus hemocyanin). Mice were immunized with P6-LPH and recombinant single-chain antibody phage display library was constructed. After 4 rounds of panning against P6-BSA and competitive inhibition enzyme immunoassay, more than 70 strains of phage antibodies capable of binding soman were obtained and 11 of them can accelerate the hydrolysis reaction of soman. One of them (EP6) was studied further. Soluble single-chain antibody was prepared and purification was performed by gel filtration and ion exchange chromatography. The kinetic experiment was carried out showing that the turnover number kcat = 198 minγ1 and the rate enhancement kcat/kuncat = 122 419. When 0.16 mg·mLγ1 EP6 was preincubated in vitro with 0.132 mmol·Lγ1 (220 g·kgγ1 = 1.1×LD95) of soman prior to the administration to mice by subcutaneous route, all animals (19 mice) survived whereas all the control mice (14) treated with PBS and soman died within 30 min. Furthermore, EP6 could prolong the latent time of spasm and death when mice were passively immunized with EP6 intravenously 15 min before 1×LD95 of soman challenge. These results demonstrate that EP6 is able to increase the rate of soman degradation and protect against soman's toxicity, especially in vitro.

  1. Hydrolysis of VX on Concrete: Rate of Degradation by Direct Surface Interrogation using an Ion Trap Secondary Ion Mass Spectrometer

    Groenewold, Gary Steven; Appelhans, Anthony David; Gresham, Garold Linn; Olson, John Eric; Rowland, B.; Williams, j.; Jeffery, M. T.


    The nerve agent VX (O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate) is lethal at very low levels of exposure, which can occur by dermal contact with contaminated surfaces. Hence, behavior of VX in contact with common urban or industrial surfaces is a subject of acute interest. In the present study, VX was found to undergo complete degradation when in contact with concrete surfaces. The degradation was directly interrogated at submonolayer concentrations by periodically performing secondary ion mass spectrometry (SIMS) analyses after exposure of the concrete to VX. The abundance of the [VX + H]+ ion in the SIMS spectra was observed to decrease in an exponential fashion, consistent with first-order or pseudo-first-order behavior. This phenomenon enabled the rate constant to be determined at 0.005 min-1 at 25 C, which corresponds to a half-life of about 3 h on the concrete surface. The decrease in [VX + H]+ was accompanied by an increase in the abundance of the principal degradation product diisopropylaminoethanethiol (DESH), which arises by cleavage of the P-S bond. Degradation to form DESH is accompanied by the formation of ethyl methylphosphonic acid, which is observable only in the negative ion spectrum. A second degradation product was also implicated, which corresponded to a diisopropylvinylamine isomer (perhaps N,N-diisopropyl aziridinium) that arose via cleavage of the S-C bond. No evidence was observed for the formation of the toxic S-2-diisopropylaminoethyl methylphosphonothioic acid. The degradation rate constants were measured at four different temperatures (24-50 C), which resulted in a linear Arrhenius relationship and an activation energy of 52 kJ mol-1. This value agrees with previous values observed for VX hydrolysis in alkaline solutions, which suggests that the degradation of submonolayer VX is dominated by alkaline hydrolysis within the adventitious water film on the concrete surface.

  2. Cyclam Derivatives with a Bis(phosphinate) or a Phosphinato-Phosphonate Pendant Arm: Ligands for Fast and Efficient Copper(II) Complexation for Nuclear Medical Applications.

    David, Tomáš; Kubíček, Vojtěch; Gutten, Ondrej; Lubal, Přemysl; Kotek, Jan; Pietzsch, Hans-Jürgen; Rulíšek, Lubomír; Hermann, Petr


    Cyclam derivatives bearing one geminal bis(phosphinic acid), -CH2PO2HCH2PO2H2 (H2L(1)), or phosphinic-phosphonic acid, -CH2PO2HCH2PO3H2 (H3L(2)), pendant arm were synthesized and studied as potential copper(II) chelators for nuclear medical applications. The ligands showed good selectivity for copper(II) over zinc(II) and nickel(II) ions (log KCuL = 25.8 and 27.7 for H2L(1) and H3L(2), respectively). Kinetic study revealed an unusual three-step complex formation mechanism. The initial equilibrium step leads to out-of-cage complexes with Cu(2+) bound by the phosphorus-containing pendant arm. These species quickly rearrange to an in-cage complex with cyclam conformation II, which isomerizes to another in-cage complex with cyclam conformation I. The first in-cage complex is quantitatively formed in seconds (pH ≈5, 25 °C, Cu:L = 1:1, cM ≈ 1 mM). At pH >12, I isomers undergo nitrogen atom inversion, leading to III isomers; the structure of the III-[Cu(HL(2))] complex in the solid state was confirmed by X-ray diffraction analysis. In an alkaline solution, interconversion of the I and III isomers is mutual, leading to the same equilibrium isomeric mixture; such behavior has been observed here for the first time for copper(II) complexes of cyclam derivatives. Quantum-chemical calculations showed small energetic differences between the isomeric complexes of H3L(2) compared with analogous data for isomeric complexes of cyclam derivatives with one or two methylphosphonic acid pendant arm(s). Acid-assisted dissociation proved the kinetic inertness of the complexes. Preliminary radiolabeling of H2L(1) and H3L(2) with (64)Cu was fast and efficient, even at room temperature, giving specific activities of around 70 GBq of (64)Cu per 1 μmol of the ligand (pH 6.2, 10 min, ca. 90 equiv of the ligand). These specific activities were much higher than those of H3nota and H4dota complexes prepared under identical conditions. The rare combination of simple ligand synthesis, very

  3. A functionalized phosphonate-rich organosilica layered hybrid material (PSLM) fabricated through a mild process for heavy metal uptake

    Daikopoulos, Chris [Department of Materials Science and Engineering, University of Ioannina, Ioannina 45110 (Greece); Bourlinos, Athanasios B. [Institute of Materials Science, NCSR “Demokritos”, Ag. Paraskevi Attikis, Athens 15310 (Greece); Georgiou, Yiannis [Laboratory of Physical Chemistry, Department of Environmental and Natural Resources Management, University of Patras, Seferi 2, Agrinio 30100 (Greece); Deligiannakis, Yiannis, E-mail: [Laboratory of Physical Chemistry, Department of Environmental and Natural Resources Management, University of Patras, Seferi 2, Agrinio 30100 (Greece); Zboril, Radek [Regional Centre of Advanced Technologies and Materials, Faculty of Science, Department of Physical Chemistry and Experimental Physics, Palacky University, Olomouc 77146 (Czech Republic); Karakassides, Michael A. [Department of Materials Science and Engineering, University of Ioannina, Ioannina 45110 (Greece)


    Highlights: • Novel phosphonate-rich organosilica layered hybrid material (PSLM) fabricated through a mild xerogel process. • Surface Complexation Modeling reveals that PSLM bears 2 types of functional groups able to bind heavy metal. • Maximum metal uptake capacities were found 2.72 mmol g{sup −1} for Cu{sup 2+}, 1.67 mmol g{sup −1} for Pb{sup 2+} and 1.00 mmol g{sup −1} for Cd{sup 2+} at pH 7. • EPR spectroscopy reveals local coordination environment for Cu{sup 2+} ions. - Abstract: A phosphonate-rich organosilica layered hybrid material (PSLM) made of 3-(trihydroxysilyl)propyl methylphosphonate, monosodium salt, as the single silica source, has been obtained from its aqueous solution through a xerogel process and mild thermal aging. The method is simple, affording bulk quantities of powdered PSLM in a single-step. The hybrid is stable in water and possesses a high content of phosphonate groups fixed on the solid matrix. In addition, PSLM shows good thermal stability, which exceeds 300 °C in air. The material was characterized using SEM, TEM, XRD, FT-IR and TGA techniques. Potentiometric titrations show that PSLM bears high-surface density of phosphonate groups (3 mmol g{sup −1}). As a result, the material displays high metal uptake capacity for heavy metal ions such as Cu{sup 2+} (2.72 mmol g{sup −1}), Pb{sup 2+} (1.67 mmol g{sup −1}) and Cd{sup 2+} (1.00 mmol g{sup −1}) at neutral pH values e.g. the pH of natural waters. Detailed theoretical modeling using a Surface Complexation Model combined with Electron Paramagnetic Resonance (EPR) spectroscopy shows that the surface distribution of surface bound Cu{sup 2+} ions is rather homogeneous e.g. copper-binding phosphonate sites are arranged in average distances 5–8 Å.

  4. Resolving pathways of interaction of mipafox and a sarin analog with human acetylcholinesterase by kinetics, mass spectrometry and molecular modeling approaches.

    Mangas, I; Taylor, P; Vilanova, E; Estévez, J; França, T C C; Komives, E; Radić, Z


    The hydroxyl oxygen of the catalytic triad serine in the active center of serine hydrolase acetylcholinesterase (AChE) attacks organophosphorus compounds (OPs) at the phosphorus atom to displace the primary leaving group and to form a covalent bond. Inhibited AChE can be reactivated by cleavage of the Ser-phosphorus bond either spontaneously or through a reaction with nucleophilic agents, such as oximes. At the same time, the inhibited AChE adduct can lose part of the molecule by progressive dealkylation over time in a process called aging. Reactivation of the aged enzyme has not yet been demonstrated. Here, our goal was to study oxime reactivation and aging reactions of human AChE inhibited by mipafox or a sarin analog (Flu-MPs, fluorescent methylphosphonate). Progressive reactivation was observed after Flu-MPs inhibition using oxime 2-PAM. However, no reactivation was observed after mipafox inhibition with 2-PAM or the more potent oximes used. A peptide fingerprinted mass spectrometry (MS) method, which clearly distinguished the peptide with the active serine (active center peptide, ACP) of the human AChE adducted with OPs, was developed by MALDI-TOF and MALDI-TOF/TOF. The ACP was detected with a diethyl-phosphorylated adduct after paraoxon inhibition, and with an isopropylmethyl-phosphonylated and a methyl-phosphonylated adduct after Flu-MPs inhibition and subsequent aging. Nevertheless, nonaged nonreactivated complexes were seen after mipafox inhibition and incubation with oximes, where MS data showed an ACP with an NN diisopropyl phosphoryl adduct. The kinetic experiments showed no reactivation of activity. The computational molecular model analysis of the mipafox-inhibited hAChE plots of energy versus distance between the atoms separated by dealkylation showed a high energy demand, thus little aging probability. However, with Flu-MPs and DFP, where aging was observed in our MS data and in previously published crystal structures, the energy demand calculated

  5. Resolving pathways of interaction of mipafox and a sarin-analog with human acetylcholinesterase by kinetics, mass spectrometry and molecular modeling approaches

    Mangas, I; Taylor, P; Vilanova, E; Estévez, J; Franca, T; Radić, Z


    The hydroxyl oxygen of the catalytic triad serine in the active center of serine hydrolase acetylcholinesterase (AChE) attacks organophosphorus compounds (OPs) at the phosphorus atom to displace the primary leaving group and to form a covalent bond. Inhibited AChE can be reactivated by cleavage of the Ser-phosphorus bond either spontaneously or through a reaction with nucleophilic agents, such as oximes. At the same time, the inhibited AChE adduct can lose part of the molecule by progressive dealkylation over time in a process called aging. Reactivation of the aged enzyme has not yet been demonstrated. Here our goal was to study oxime reactivation and aging reactions of human AChE inhibited by mipafox or a sarin analog (Flu-MPs, fluorescent methylphosphonate). Progressive reactivation was observed after Flu-MPs inhibition using oxime 2-PAM. However, no reactivation was observed after mipafox inhibition with 2-PAM or the more potent oximes used. A peptide mass fingerprinted mass spectrometry (MS) method, which clearly distinguished the peptide with the active serine (active center peptide, ACP) of the human AChE adducted with OPs, was developed by MALDI-TOF and MALDI-TOF-TOF. The ACP was detected with a diethyl phosphorylated adduct after paraoxon inhibition, and with an isopropylmethyl phosphonylated and a methyl phosphonylated adduct after Flu-MPs inhibition and subsequent aging. Nevertheless, nonaged nonreactivated complexes were seen after mipafox inhibition and incubation with oximes, where MS data showed an ACP with an NN diidopropyl phosphoryl adduct. The kinetic experiments showed no reactivation of activity. The computational molecular model analysis of the mipafox-inhibited hAChE plots of energy versus distance between the atoms separated by dealkylation showed a high energy demand, thus little aging probability. However with Flu-MPs and DFP, where aging was observed in our MS data and in previously published crystal structures, the energy demand

  6. Theoretical Analysis on Response Mechanism of Polymer-Coated Shear Horizontal Surface Acoustic Wave Gas Sensor%覆盖聚合物敏感膜的水平剪切型声表面波气体传感器机理分析

    谢晓; 王文; 刘明华; 何世堂


    采用微扰理论分析了覆盖聚合物敏感膜的水平剪切型声表面波气体传感器(SH-SAW)的响应机理.以针对有机磷毒剂具有良好选择性的含氟多羟基聚硅氧烷(FPOL)膜材料为例,分析了聚合物膜厚以及传感器工作频率在敏感膜吸附气体时对传感器响应的影响.计算结果表明,SH-SAW气体传感器对于不同浓度的甲基磷酸二甲酯(DMMP)气体响应随FPOL膜厚和传感器工作频率的改变呈现非线性变化.为了获得线性特性的传感器响应及较小的声波衰减,在一定的DMMP气体浓度检测范围内,通过理论计算提取出了优化的FPOL敏感膜膜厚和传感器工作频率等参数.%The response mechanism of polymer-coated shear horizontal surface acoustic wave (SH-SAW) sensor was analyzed based on the perturbation approach. Using fluoropolyol ( FPOL) as the sensitive detector for organophosphorus agents,the sensor response of the gas adsorption was analyzed as a function of the thickness of the polymer and the operating frequency of SH-SAW device. Calculation results indicate that the SH-SAW gas sensor has non-linear response for various concentrations of dimethyl methylphosphonate ( DMMP) with different FPOL thickness and operating frequency. To obtain a monotone gas sensor response and low acoustic attenuation, the optimal parameters including the FPOL thickness and the operating frequency were determined theoretically.

  7. Development of a gas-cylinder-free plasma desorption/ionization system for on-site detection of chemical warfare agents.

    Iwai, Takahiro; Kakegawa, Ken; Aida, Mari; Nagashima, Hisayuki; Nagoya, Tomoki; Kanamori-Kataoka, Mieko; Miyahara, Hidekazu; Seto, Yasuo; Okino, Akitoshi


    A gas-cylinder-free plasma desorption/ionization system was developed to realize a mobile on-site analytical device for detection of chemical warfare agents (CWAs). In this system, the plasma source was directly connected to the inlet of a mass spectrometer. The plasma can be generated with ambient air, which is drawn into the discharge region by negative pressure in the mass spectrometer. High-power density pulsed plasma of 100 kW could be generated by using a microhollow cathode and a laboratory-built high-intensity pulsed power supply (pulse width: 10-20 μs; repetition frequency: 50 Hz). CWAs were desorbed and protonated in the enclosed space adjacent to the plasma source. Protonated sample molecules were introduced to the mass spectrometer by airflow through the discharge region. To evaluate the analytical performance of this device, helium and air plasma were directly irradiated to CWAs in the gas-cylinder-free plasma desorption/ionization system and the protonated molecules were analyzed by using an ion-trap mass spectrometer. A blister agent (nitrogen mustard 3) and nerve gases [cyclohexylsarin (GF), tabun (GA), and O-ethyl S-2-N,N-diisopropylaminoethyl methylphosphonothiolate (VX)] in solution in n-hexane were applied to the Teflon rod and used as test samples, after solvent evaporation. As a result, protonated molecules of CWAs were successfully observed as the characteristic ion peaks at m/z 204, 181, 163, and 268, respectively. In air plasma, the limits of detection were estimated to be 22, 20, 4.8, and 1.0 pmol, respectively, which were lower than those obtained with helium plasma. To achieve quantitative analysis, calibration curves were made by using CWA stimulant dipinacolyl methylphosphonate as an internal standard; straight correlation lines (R(2) = 0.9998) of the peak intensity ratios (target per internal standard) were obtained. Remarkably, GA and GF gave protonated dimer ions, and the ratios of the protonated dimer ions to the protonated

  8. Analysis of chemical warfare agents in organic liquid samples with magnetic dispersive solid phase extraction and gas chromatography mass spectrometry for verification of the chemical weapons convention.

    Singh, Varoon; Purohit, Ajay Kumar; Chinthakindi, Sridhar; Goud, Raghavender D; Tak, Vijay; Pardasani, Deepak; Shrivastava, Anchal Roy; Dubey, Devendra Kumar


    A simple, sensitive and low temperature sample preparation method is developed for detection and identification of Chemical Warfare Agents (CWAs) and scheduled esters in organic liquid using magnetic dispersive solid phase extraction (MDSPE) followed by gas chromatography-mass spectrometry analysis. The method utilizes Iron oxide@Poly(methacrylic acid-co-ethylene glycol dimethacrylate) resin (Fe2O3@Poly(MAA-co-EGDMA)) as sorbent. Variants of these sorbents were prepared by precipitation polymerization of methacrylic acid-co-ethylene glycol dimethacrylate (MAA-co-EGDMA) onto Fe2O3 nanoparticles. Fe2O3@poly(MAA-co-EGDMA) with 20% MAA showed highest recovery of analytes. Extractions were performed with magnetic microspheres by MDSPE. Parameters affecting the extraction efficiency were studied and optimized. Under the optimized conditions, method showed linearity in the range of 0.1-3.0μgmL(-1) (r(2)=0.9966-0.9987). The repeatability and reproducibility (relative standard deviations (RSDs) %) were in the range of 4.5-7.6% and 3.4-6.2% respectively for organophosphorous esters in dodecane. Limits of detection (S/N=3/1) and limit of quantification (S/N=10/1) were found to be in the range of 0.05-0.1μgmL(-1) and 0.1-0.12μgmL(-1) respectively in SIM mode for selected analytes. The method was successfully validated and applied to the extraction and identification of targeted analytes from three different organic liquids i.e. n-hexane, dodecane and silicon oil. Recoveries ranged from 58.7 to 97.3% and 53.8 to 95.5% at 3μgmL(-1) and 1μgmL(-1) spiking concentrations. Detection of diethyl methylphosphonate (DEMP) and O-Ethyl S-2-diisopropylaminoethyl methylphosphonothiolate (VX) in samples provided by the Organization for Prohibition of Chemical Weapons Proficiency Test (OPCW-PT) proved the utility of the developed method for the off-site analysis of CWC relevant chemicals.

  9. Self-Decontaminating Fibrous Materials Reactive toward Chemical Threats.

    Bromberg, Lev; Su, Xiao; Martis, Vladimir; Zhang, Yunfei; Hatton, T Alan


    Polymers that possess highly nucleophilic pyrrolidinopyridine (Pyr) and primary amino (vinylamine, VAm) groups were prepared by free-radical copolymerization of N,N-diallylpyridin-4-amine (DAAP) and N-vinylformamide (NVF) followed by acidic hydrolysis of NVF into VAm. The resulting poly(DAAP-co-VAm-co-NVF) copolymers were water-soluble and reacted with water-dispersible polyurethane possessing a high content of unreacted isocyanate groups. Spray-coating of the nylon-cotton (NYCO), rayon, and poly(p-phenylene terephthalamide) (Kevlar 119) fibers pretreated with phosphoric acid resulted in covalent bonding of the polyurethane with the hydroxyl groups on the fiber surface. A second spray-coating of aqueous solutions of poly(DAAP-co-VAm-co-NVF) on the polyurethane-coated fiber enabled formation of urea linkages between unreacted isocyanate groups of the polyurethane layer and the amino groups of poly(DAAP-co-VAm-co-NVF). Fibers with poly(DAAP-co-VAm-co-NVF) attached were compared with fibers modified by adsorption of water-insoluble poly(butadiene-co-pyrrolidinopyridine) (polyBPP) in terms of the stability against polymer leaching in aqueous washing applications. While the fibers modified by attachment of poly(DAAP-co-VAm-co-NVF) exhibited negligible polymer leaching, over 65% of adsorbed polyBPP detached and leached from the fibers within 7 days. Rayon fibers modified by poly(DAAP-co-VAm-co-NVF) were tested for sorption of dimethyl methylphosphonate (DMMP) in the presence of moisture using dynamic vapor sorption technique. Capability of the fibers modified with poly(DAAP-co-VAm-co-NVF) to facilitate hydrolysis of the sorbed DMMP in the presence of moisture was uncovered. The self-decontaminating property of the modified fibers against chemical threats was tested using a CWA simulant diisopropylfluorophosphate (DFP) in aqueous media at pH 8.7. Fibers modified with poly(DAAP-co-VAm-co-NVF) facilitated hydrolysis of DFP with the half-lives up to an order of magnitude

  10. 4-(2-aminooxyethoxy)-2-(ethylureido)quinoline-oligonucleotide conjugates: synthesis, binding interactions, and derivatization with peptides.

    Hamma, Tomoko; Miller, Paul S


    Oligo-2'-O-methylribonucleotides conjugated with 4-(2-aminooxyethoxy)-2-(ethylureido)quinoline (AOQ) and 4-ethoxy-2-(ethylureido)quinoline (EOQ) were prepared by reaction of the AOQ or EOQ phosphoramidite with the protected oligonucleotide on a controlled pore glass support. Deprotection with ethylenediamine enabled successful isolation and purification of the highly reactive AOQ-conjugated oligomer. Polyacrylamide gel electrophoresis mobility shift experiments showed that the dissociation constants of complexes formed between an AOQ- or EOQ-conjugated 8-mer and complementary RNA or 2'-O-methyl-RNA targets (9- and 10-mers) were in the low nM concentration range at 37 degrees C, whereas no binding was observed for the corresponding nonconjugated oligomer, even at a concentration of 500 nM. Fluorescence studies suggested that this enhanced affinity is most likely due to the ability of the quinoline ring of the AOQ or EOQ group to stack on the last base pair formed between the oligomer and target, thus stabilizing the duplex. The binding affinity of a 2'-O-methyl RNA 15-mer, which contained an alternating methylphosphonate/phosphodiester backbone, for a 59-nucleotide stem-loop HIV TAR RNA target, increased 2.3 times as a consequence of conjugation with EOQ. The aminooxy group of AOQ-conjugated oligomers is a highly reactive nucleophile, which reacts readily with aldehydes and ketones to form stable oxime derivatives. This feature was used to couple an AOQ-oligomer with leupeptin, a tripeptide that contains a C-terminus aldehyde group. A simple method was developed to introduce a ketone functionality into peptides that contain a cysteine residue by reacting the peptide with bromoacetone. The resulting keto-peptide was then coupled to the AOQ-oligomer. This procedure was used to prepare oligonucleotide conjugates of a tetrapeptide, RGDC, and a derivative of HIV tat peptide having a C-terminus cysteine. The combination of the unique reactivity of the aminooxy group and

  11. Seasonal and spatial dynamic of current-use pesticides (CUPs) in an Argentinian watershed.

    Perez, Debora; Okada, Elena; Menone, Mirta; Aparicio, Virginia; Costa, Jose Luis


    The Argentinian Pampa region is the major agricultural zone, in which, the agricultural lands are strongly linked to surface waters. However, Argentina has not regulation for most of the current -used pesticides (CUPs) in surface water to protect the aquatic life. The objective of this work was to study the seasonal and spatial variations of CUPs in surface waters of "El Crespo" stream, and to determine the maximum levels reached to evaluate the possible impact on aquatic life. "El Crespo" stream is only influenced by farming activities, with intensive crop systems upstream (US) and extensive livestock production downstream (DS). It is an optimal site for pesticide monitoring studies since there are no urban or industrial inputs into the system. Water samples were collected monthly from October 2014 to October 2015 in the US and DS sites by triplicate using 1 L polypropylene bottles and stored at -20°C until analysis. The samples were analyzed using liquid chromatography coupled to a tandem mass spectrometer (UPLC-MS/MS). The most frequently detected residues (>40%) were glyphosate (GLY) and its metabolite amino methylphosphonic acid (AMPA), atrazine, acetochlor, metolachlor, 2,4-D, metsulfuron methyl, fluorocloridone, imidacloprid, tebuconazole and epoxiconazole, which are used in the crops cultivated in the area (i.e. soybean, potato, maize and wheat). Individual analysis showed that the herbicide GLY and its metabolite AMPA presented seasonal and spatial variations. The highest concentrations of GLY and AMPA were detected in US site during spring 2014 (2.09 ± 0.39 and 1.13 ± 0.56 µg/L, respectively) and in DS during summer 2015 (1.06 ± 1.02 and 0.20 ± 0.23 µg/L). Comparing total CUPs concentration between sites, a significant increase in UP site during spring 2014 (4.03 ± 0.43 µg/L) in relation to DS (1.54 ± 1.17 µg/L) was observed, may be due to pesticide applications during fallow and transport via surface runoff. Data generated in the present

  12. Research on Properties of Rigid Polyurethane Foam Plastics Modiifed by Composite Flame Retardant%复合阻燃剂阻燃硬质聚氨酯泡沫塑料的性能研究

    张忠厚; 王银涛; 杨光; 冯丽; 闫春绵


    Rigid polyurethane(PUR-R) foam plastics modified by composite flame retardant were prepared. Effects of composite flame retardant dimethyl methylphosphonate(DMMP),trichloropropylphosphate(TCPP),expandable graphite(EG) and aluminum hydroxide(ATH) on the properties of PUR-R foam plastics modified by composite flame retardant were studied. The optimum proportion of the composite flame retardant was determined with orthogonal experiment. The limited oxygen index(LOI), the smoke density rating and the compressive strength were obtained by LOI instrument,smoke density determinator and material testing machine. The results show that when the mass ratio of DMMP,TCPP,EG,ATH are 2∶2∶3∶3,12 phr composite flame retardant is added to 25 phr polyether polyols,the LOI,the smoke density rating and the compressive strength of PUR-R foam plastics modified by composite flame retardant are 26.3%,77.63 and 0.18 MPa respectively,PUR-R foam plastics modified by composite flame retardant have better comprehensive properties .%制备了复合阻燃剂阻燃硬质聚氨酯(PUR-R)泡沫塑料,研究了复合阻燃剂甲基膦酸二甲酯(DMMP)、三(2-氯异丙基)磷酸酯(TCPP)、可膨胀型石墨(EG)和氢氧化铝(ATH)对PUR-R泡沫塑料阻燃性能的影响,采用正交试验确定了复合阻燃剂的最佳配比。用极限氧指数(LOI)测定仪、烟密度测定仪和万能试验机测定了阻燃PUR-R泡沫塑料的LOI、烟密度等级和压缩强度,结果表明,当DMMP,TCPP,EG,ATH的质量比为2∶2∶3∶3时,在25份聚醚多元醇中添加12份复合阻燃剂,制备的阻燃PUR-R泡沫塑料的LOI达26.3%,烟密度等级为77.63,压缩强度为0.18 MPa,阻燃PUR-R泡沫塑料具有良好的综合性能。

  13. Rapid and efficient filtration-based procedure for separation and safe analysis of CBRN mixed samples.

    Mostafa Bentahir

    Full Text Available Separating CBRN mixed samples that contain both chemical and biological warfare agents (CB mixed sample in liquid and solid matrices remains a very challenging issue. Parameters were set up to assess the performance of a simple filtration-based method first optimized on separate C- and B-agents, and then assessed on a model of CB mixed sample. In this model, MS2 bacteriophage, Autographa californica nuclear polyhedrosis baculovirus (AcNPV, Bacillus atrophaeus and Bacillus subtilis spores were used as biological agent simulants whereas ethyl methylphosphonic acid (EMPA and pinacolyl methylphophonic acid (PMPA were used as VX and soman (GD nerve agent surrogates, respectively. Nanoseparation centrifugal devices with various pore size cut-off (30 kD up to 0.45 µm and three RNA extraction methods (Invisorb, EZ1 and Nuclisens were compared. RNA (MS2 and DNA (AcNPV quantification was carried out by means of specific and sensitive quantitative real-time PCRs (qPCR. Liquid chromatography coupled to time-of-flight mass spectrometry (LC/TOFMS methods was used for quantifying EMPA and PMPA. Culture methods and qPCR demonstrated that membranes with a 30 kD cut-off retain more than 99.99% of biological agents (MS2, AcNPV, Bacillus Atrophaeus and Bacillus subtilis spores tested separately. A rapid and reliable separation of CB mixed sample models (MS2/PEG-400 and MS2/EMPA/PMPA contained in simple liquid or complex matrices such as sand and soil was also successfully achieved on a 30 kD filter with more than 99.99% retention of MS2 on the filter membrane, and up to 99% of PEG-400, EMPA and PMPA recovery in the filtrate. The whole separation process turnaround-time (TAT was less than 10 minutes. The filtration method appears to be rapid, versatile and extremely efficient. The separation method developed in this work constitutes therefore a useful model for further evaluating and comparing additional separation alternative procedures for a safe handling and

  14. Environmental Fate of Organophosphorus Compounds Related to Chemical Weapons

    Davisson, M L; Love, A H; Vance, A; Reynolds, J G


    chloride and hydroxyl (strong nucleophile) dominated experimental solutions. Because of its overwhelming abundance in solution relative to hydroxyl ion, bicarbonate likely effectively competes in nucleophilic attack on phosphorus. The addition of natural dissolved organic matter at 100 mg/L in pH 7 bicarbonate buffered solution slowed VX hydrolysis rates {approx}2 times relative to controls, suggesting hydrophobic interaction. Adsorption experiments derived isotherms from batch aqueous experiments on montmorillonite clay, iron-oxyhydroxide goethite, and on amorphous silica. VX had moderate affinity for montmorillonite and amorphous silica, and very low affinity toward goethite. The addition of dissolved organic matter into solution enhanced VX adsorption to goethite, consistent with its high affinity for hydrophobic organic matter (log K{sub oc} = 2.52). Diisopropylaminoethylthiol (DESH), a hydrolysis product of VX showed equivalent adsorption to montmorillonite, and poor affinity to goethite and silica. However, hydrolysis products O-Ethylmethylphosphonic acid (EMPA) and methylphosphonic acid (MPA) strongly adsorbed on goethite, but not on montmorillonite or silica, suggesting a ligand-exchange mechanism. VX degraded rapidly when completely dried onto goethite followed by rehydration, consistent with an irreversible chemical adsorption mechanism.

  15. Lithium Polymer Electrolytes Based On PMMA / PEG And Penetrant Diffusion In Kraton Penta-Block Ionomer

    Meng, Yan

    permeability to hazardous organic chemicals. In addition, this work also contributes to study of polymer electrolyte membrane for fuel cell systems, because water transport in polymer electrolyte membranes (PEMs) has a profound effect on the performance of a fuel cell, yet is surprisingly the least studied property of PEMs[19]. The self-diffusion coefficients of different penetrant molecules, i.e., water, dimethyl methylphosphonate (DMMP), and ethanol in the said ionomer were accurately measured with PFG NMR as functions of temperature and concentration of solvents. Water exhibited self-diffusion coefficients two orders of magnitude higher than DMMP, while ethanol lies in between. Their effective volume to surface ratios of domains where diffusion took place were determined. The volume to surface ratios of water and DMMP are quite different, suggesting they may have different local geometry of the pores they reside in, while the V p/Seff ratios for water and ethanol are similar, thereby suggesting similar local environments of these solvents in the ionomer.