1832-54-8Relevant articles and documents
Enzymes for the homeland defense: Optimizing phosphotriesterase for the hydrolysis of organophosphate nerve agents
Tsai, Ping-Chuan,Fox, Nicholas,Bigley, Andrew N.,Harvey, Steven P.,Barondeau, David P.,Raushel, Frank M.
, p. 6463 - 6475 (2012)
Phosphotriesterase (PTE) from soil bacteria is known for its ability to catalyze the detoxification of organophosphate pesticides and chemical warfare agents. Most of the organophosphate chemical warfare agents are a mixture of two stereoisomers at the phosphorus center, and the SP-enantiomers are significantly more toxic than the RP-enantiomers. In previous investigations, PTE variants were created through the manipulation of the substrate binding pockets and these mutants were shown to have greater catalytic activities for the detoxification of the more toxic SP-enantiomers of nerve agent analogues for GB, GD, GF, VX, and VR than the less toxic R P-enantiomers. In this investigation, alternate strategies were employed to discover additional PTE variants with significant improvements in catalytic activities relative to that of the wild-type enzyme. Screening and selection techniques were utilized to isolate PTE variants from randomized libraries and site specific modifications. The catalytic activities of these newly identified PTE variants toward the SP-enantiomers of chromophoric analogues of GB, GD, GF, VX, and VR have been improved up to 15000-fold relative to that of the wild-type enzyme. The X-ray crystal structures of the best PTE variants were determined. Characterization of these mutants with the authentic G-type nerve agents has confirmed the expected improvements in catalytic activity against the most toxic enantiomers of GB, GD, and GF. The values of kcat/Km for the H257Y/L303T (YT) mutant for the hydrolysis of GB, GD, and GF were determined to be 2 ×106, 5 ×105, and 8 ×105 M-1 s-1, respectively. The YT mutant is the most proficient enzyme reported thus far for the detoxification of G-type nerve agents. These results support a combinatorial strategy of rational design and directed evolution as a powerful tool for the discovery of more efficient enzymes for the detoxification of organophosphate nerve agents.
Inhibition of plasma cholinesterase by O-alkylfluorophosphonates
Cabal, Jiri,Kassa, Jiri,Patocka, Jiri
, p. 521 - 526 (1997)
Inhibition of plasma cholinesterase by three methylfluorophosphonates (MFF), sarin, soman and cyclosin, and by the products of their hydrolysis and alcoholysis was examined. Inhibition by phosphonic acids and by methyl esters derived from MFF was purely competitive while that by MFF was irreversible. The rate of phosphorylation of cholinesterase by MFF differs, depending on the structure of the alkoxy group in the MFF and decreases in the sequence soman-sarin-cyclosin. The affinity values of MFF, phosphonic acids and methyl esters of phosphonic acid for cholinesterase are comparable. The in vitro kinetic parameters suggest that plasma cholinesterase might act as a natural detoxicating agent in cases of poisoning with the above inhibitors of acetylcholinesterase.
Quantitative analysis of chemical warfare agent degradation products in reaction masses using capillary electrophoresis
Nassar, Alaa-Eldin F.,Lucas, Samuel V.,Myler, Craig A.,Jones, William R.,Campisano, Michael,Hoffland, Lynn D.
, p. 3598 - 3604 (1998)
Quantitative methods have been developed for the analysis of chemical warfare agent degradation products in reaction masses using capillary electrophoresis (CE). This is the first report of a systematic validation of a CE-based method for the analysis of chemical warfare agent degradation products in agent neutralization matrixes (reaction masses). After neutralization with monoethanolamine/ water, the nerve agent GB (isopropyl methylphosphonofluoridate, Sarin) gives isopropyl methylphosphonic acid (IMPA) and O-isopropyl O′-(2-amino)ethyl methylphosphonate (GB-MEA adduct). The nerve agent GD (pinacolyl methylphosphonofluoridate, Soman), [pinacolyl = 2-(3,3-dimethyl)butyl] produces pinacolyl methylphosphonic acid (PMPA) and O-pinacolyl O′-(2-amino)ethyl methylphosphonate (GD-MEA adduct). The samples were prepared by dilution of the reaction masses with deionized water before analysis by CE/indirect UV detection or CE/conductivity detection. Migration time precision was less than 4.0% RSD for IMPA and 5.0% RSD for PMPA on a day-to-day basis. The detection limit for both IMPA and PMPA is 100 μg/L; the quantitation limit for both is 500 μg/L. For calibration standards, IMPA and PMPA gave a linear response (R2 = 0.9999) over the range 0.5-100 μg/mL. The interday precision RSDs were 1.9, 1.0, and 0.7% for IMPA at 7.5, 37.5 and 75.0 μg/mL, respectively. Corresponding values for PMPA (again, RSD) were 2.9, 1.1, and 1.0% at 7.5, 37.5 and 87.5 μg/mL, respectively, as before. Analysis accuracy was assessed by spiking actual neutralization samples with IMPA or PMPA. For IMPA, the seven spike levels used ranged from 20 to 220% of the IMPA background level, and the incremental change in the found IMPA level ranged from 86 to 99% of the true spiking increment (R2 = 0.9987 for the linear regression). For PMPA, the five spike levels ranged from 10 to 150% of the matrix background level, and similarly, the accuracy obtained ranged from 95 to 97% of the true incremental value (R2 = 0.9999 for the linear regression).
Kinetics of destruction of diisopropyl methylphosphonate in corona discharge
Korobeinichev, Oleg P.,Chernov, Anatoly A.,Sokolov, Vladimir V.,Krasnoperov, Lev N.
, p. 331 - 337 (2002)
The kinetics of the destruction of diisopropyl methylphosphonate (DIMP) in corona discharge has been studied using a flow tubular coaxial wire dielectric barrier corona discharge reactor. The identification and quantitative determination of DIMP, its destruction intermediates, and phosphorus-containing destruction products were performed using molecular beam mass spectrometry and gas chromatography/mass spectrometry. Active discharge power was varied in the range 0.01-5 W. The destruction products such as isopropyl methylphosphonate, methylphosphonic acid, and orthophosphoric acid were found on the reactor walls. The dependence of the extent of the destruction, D(D = 1 - X/X0, where X and X0 are DIMP mole fractions at the outlet and the inlet of the reactor), on the specific energy deposition Ex(Ex = PF-1 X0-1, where F is the carrier gas flow and P is the power dissipated in discharge reactor) was measured over the DIMP mole fraction range 60-500 ppm at the pressure of 1 bar and the temperature of 340 K. Over the range of the experimental conditions studied the destruction obeys the pseudo-first-order kinetic law: 1n(1 - D) = -KEx. Plausible mechanisms of the destruction are discussed. It was concluded that ion mechanism is the major one responsible for the destruction process.
Microwave-assisted ionic liquid-catalyzed selective monoesterification of alkylphosphonic acids—an experimental and a theoretical study
ábrányi-Balogh, Péter,Drahos, László,Harsági, Nikoletta,Henyecz, Réka,Keglevich, Gy?rgy
, (2021/09/07)
It is well-known that the P-acids including phosphonic acids resist undergoing direct es-terification. However, it was found that a series of alkylphoshonic acids could be involved in mo-noesterification with C2–C4 alcohols under microwave (MW) irradiation in the presence of [bmim][BF4] as an additive. The selectivity amounted to 80–98%, while the isolated yields fell in the range of 61–79%. The method developed is a green method for P-acid esterification. DFT calculations at the M062X/6–311+G (d,p) level of theory (performed considering the solvent effect of the corresponding alcohol) explored the three-step mechanism, and justified a higher enthalpy of activation (160.6–194.1 kJ·mol–1) that may be overcome only by MW irradiation. The major role of the [bmim][BF4] additive is to increase the absorption of MW energy. The specific chemical role of the [BF4] anion of the ionic liquid in an alternative mechanism was also raised by the computations.
Selective detection of chemical warfare agents VX and Sarin by the short wavelength inner filter technique (SWIFT)
Redy Keisar, Orit,Pevzner, Alexander,Baheti, Abhishek,Vigalok, Arkadi,Ashkenazi, Nissan
, p. 15040 - 15043 (2020/12/22)
A novel SWIFT-based strategy for fluorimetric detection of practical amounts (minimal effective dose or lower) of chemical warfare agents is reported. This strategy employs readily available reagents and allows distinguishing between the V and G agents, as well as their discrimination from potential interferents. This journal is
Investigating the breakdown of the nerve agent simulant methyl paraoxon and chemical warfare agents GB and VX using nitrogen containing bases
Wilson, Craig,Cooper, Nicholas J.,Briggs, Michael E.,Cooper, Andrew I.,Adams, Dave J.
supporting information, p. 9285 - 9291 (2019/01/03)
A range of nitrogen containing bases was tested for the hydrolysis of a nerve agent simulant, methyl paraoxon (MP), and the chemical warfare agents, GB and VX. The product distribution was found to be highly dependant on the basicity of the base and the quantity of water used for the hydrolysis. This study is important in the design of decontamination technology, which often involve mimics of CWAs.
BLOCK COPOLYMER COMPLEX COACERVATE CORE MICELLES FOR ENZYMATIC CATALYSIS IN ORGANIC SOLVENT
-
Sheet 1/27, (2016/04/09)
Disclosed are complex coacervate core micelles comprising an enzyme capable of hydrolyzing organophosphorous compounds, such as nerve agents, and, for example, their use in remediation or decontamination of stockpiles of chemical weapons.
Experimental and theoretical studies of hydrolysis of nerve agent sarin by binuclear zinc biomimetic catalysts
Guo, Nan,Zhong, Jin-Yi,Chen, Shi-Lu,Liu, Jing-Quan,Min, Qi,Shi, Rui-Xue
, p. 70 - 77 (2015/06/16)
A complex (ZnL1) of 2,2-(2-hydroxy-5-methyl-1,3-phenylene)bis(methylene)bis ((pyridin-2-ylmethyl)azanediyl)diethanol (this ligand is named by L1) functionalized with two Zn(II) centers, has been previously suggested to be a structural model for binuclear
Molecular engineering of organophosphate hydrolysis activity from a weak promiscuous lactonase template
Meier, Monika M.,Rajendran, Chitra,Malisi, Christoph,Fox, Nicholas G.,Xu, Chengfu,Schlee, Sandra,Barondeau, David P.,Hoecker, Birte,Sterner, Reinhard,Raushel, Frank M.
supporting information, p. 11670 - 11677 (2013/09/02)
Rapid evolution of enzymes provides unique molecular insights into the remarkable adaptability of proteins and helps to elucidate the relationship between amino acid sequence, structure, and function. We interrogated the evolution of the phosphotriesteras
