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.
Gustafson,Martell
, p. 2309 (1962)
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).
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.
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.
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
