Molecular orbital calculations on the P?S bond cleavage step in the hydroperoxidolysis of nerve agent VX

Patterson, Eric V.; Cramer, Christopher J.

doi:10.1002/(sici)1099-1395(199804)11:4<232::aid-poc984>3.0.co;2-a

Cited by 26 publications

(33 citation statements)

References 88 publications

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“…The SES approximation has served as the basis of a number of previous investigations ,,,,,,,− of solvation effects on barriers using conventional or variational transition state theory. Some recent examples employing implicit-solvent methods are given in Table , which uses the same conventions as Table .…”

Section: 12 Ses and Esp Applicationsmentioning

confidence: 99%

Implicit Solvation Models: Equilibria, Structure, Spectra, and Dynamics

1999

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Section: 12 Ses and Esp Applicationsmentioning

confidence: 99%

Implicit Solvation Models: Equilibria, Structure, Spectra, and Dynamics

1999

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“…Theoretical calculations have demonstrated that a stable pentacoordinate intermediate is formed during P-S bond peroxidolysis of an analogue of VX in aqueous solution. 18 Whether this also occurs during the hydrolysis of phosphorothiolate pesticides, which differ in that they do not possess any phosphonate bonds, is still unknown.…”

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The effects of substrate orientation on the mechanism of a phosphotriesterase

et al. 2005

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While the underlying chemistry of enzyme-catalyzed reactions may be almost identical, the actual turnover rates of different substrates can vary significantly. This is seen in the turnover rates for the catalyzed hydrolysis of organophosphates by the bacterial phosphotriesterase OpdA. We investigate the variation in turnover rates by examining the hydrolysis of three classes of substrates: phosphotriesters, phosphothionates, and phosphorothiolates. Theoretical calculations were used to analyze the reactivity of these substrates and the energy barriers to their hydrolysis. This information was then compared to information derived from enzyme kinetics and crystallographic studies, providing new insights into the mechanism of this enzyme. We demonstrate that the enzyme catalyzes the hydrolysis of organophosphates through steric constraint of the reactants, and that the equilibrium between productively and unproductively bound substrates makes a significant contribution to the turnover rate of highly reactive substrates. These results highlight the importance of correct orientation of reactants within the active sites of enzymes to enable efficient catalysis.

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“…Fig 9. Reaction coordinate diagram for the addition-elimination process which was not observed during the gas phase reaction of HOO − anion with DMMP.…”

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Reactions of the hydroperoxide anion with dimethyl methylphosphonate in an ion trap mass spectrometer: evidence for a gas phase α-effect

2008

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The gas phase degradation reactions of the chemical warfare agent (CWA) simulant, dimethyl methylphosphonate (DMMP), with the hydroperoxide anion (HOO(-)) were investigated using a modified quadrupole ion trap mass spectrometer. The HOO(-) anion reacts readily with neutral DMMP forming two significant product ions at m/z 109 and m/z 123. The major reaction pathways correspond to (i) the nucleophilic substitution at carbon to form [CH(3)P(O)(OCH(3))O](-) (m/z 109) in a highly exothermic process and (ii) exothermic proton transfer. The branching ratios of the two reaction pathways, 89% and 11% respectively, indicate that the former reaction is significantly faster than the latter. This is in contrast to the trend for the methoxide anion with DMMP, where proton transfer dominates. The difference in the observed reactivities of the HOO(-) and CH(3)O(-) anions can be considered as evidence for an alpha-effect in the gas phase and is supported by electronic structure calculations at the B3LYP/aug-cc-pVTZ//B3LYP/6-31+G(d) level of theory that indicate the S(N)2(carbon) process has an activation energy 7.8 kJ mol(-1) lower for HOO(-) as compared to CH(3)O(-). A similar alpha-effect was calculated for nucleophilic addition-elimination at phosphorus, but this process--an important step in the perhydrolysis degradation of CWAs in solution--was not observed to occur with DMMP in the gas phase. A theoretical investigation revealed that all processes are energetically accessible with negative activation energies. However, comparison of the relative Arrhenius pre-exponential factors indicate that substitution at phosphorus is not kinetically competitive with respect to the S(N)2(carbon) and deprotonation processes.

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Molecular orbital calculations on the P?S bond cleavage step in the hydroperoxidolysis of nerve agent VX

Cited by 26 publications

References 88 publications

Implicit Solvation Models: Equilibria, Structure, Spectra, and Dynamics

Implicit Solvation Models: Equilibria, Structure, Spectra, and Dynamics

The effects of substrate orientation on the mechanism of a phosphotriesterase

Reactions of the hydroperoxide anion with dimethyl methylphosphonate in an ion trap mass spectrometer: evidence for a gas phase α-effect

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