Ab Initio Molecular Orbital and Density Functional Studies on the Solvolysis of Sarin and <i>O,S</i>-Dimethyl Methylphosphonothiolate, a VX-like Compound

Šečkutė, Jolita; Menke, Jessica L.; Emnett, Ryan J.; Patterson, Eric V.; Cramer, Christopher J.

doi:10.1021/jo0502706

Cited by 75 publications

(24 citation statements)

References 76 publications

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“…Posteriormente, estudamos as duas reações mais comuns no processo de hidrólise alcalina desse agente neurotóxico: a quebra das ligações P-S e P-O 1 47 Apresentamos na Tabela 3 toda a análise termodinâmica na temperatura ambiente (298 K) para as reações H1 e H2. Entretanto, é relatado na literatura que a cinética reacional é desfavorável: 50% de VX é degradado em 78 horas a 295 K.…”

Section: Degradação Do Agente Neurotóxico Vx Por óXido De Magnésiounclassified

Theoretical Chemistry at the Service of the Chemical Defense: Degradation of Nerve Agents in Magnesium Oxide and Hydroxide Surface

Alvim¹,

Vaiss²,

Leitão³

et al. 2014

Revista Virtual De Química

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Abstract:The Pró-Defesa funding of projects was a joint initiative of CAPES and the Ministry of Defense to fund research in defense. In this article we review the main scientific results obtained in the project "Formação de Pessoal Qualificado em Química Quântica Computacional para Atuação na Área de Defesa Química", funded by the first edition of Pró-Defesa in 2005, which involved a collaboration between the Departments of Chemistry of the Federal University of Juiz de Fora and of the Military Institute of Engineering. The main goal of this project was to study, using theoretical-computational methods, the potential of magnesium oxide and hydroxide surfaces to degrade organophosphorus (OP) substances used as warfare agents, also known as neurotoxics. These substances inhibit the acetylcholinesterase, enzyme of fundamental role in the central nervous system. The VX (O-ethyl-S-(2-diisopropylethylamino) ethyl methylphosphonothioate) and sarin (isopropyl methylphosphonofluoridate) agents are some of the main neurotoxic agents, thus the search for ways to degrade them is considerably important. In this paper, we present theoretical investigations of two chemical degradation processes of organophosphates: the hydrolysis of a VX-like OP compound (O,S-dimethyl methylphosphonothioate, DMPT) by the dissociative chemisorption on the MgO(001) surface and the degradation of sarin by a surface of magnesium hydroxide Mg(OH) 2 , known as brucite. These processes were studied by the combination of density functional theory (DFT) with periodic boundary conditions, an approach that is the state of the art of the theoretical methods for this type of problem. In the case of DMPT, we proposed a degradation mechanism that involves degradation reactions of DMPT and water molecules in the presence of two types of MgO(001) surface models: terrace and Al-doped. Conformations, free energy differences, transition states and reaction barriers were calculated. We showed that the MgO(001) surface acts as a possible catalyst for the degradation of VX, but with higher selectivity than the Al-doped surface when compared with sites without defects on the terrace. These results may have important applications as well as to serve as reference for further studies on the decomposition of VX. In the degradation process of sarin using brucite, we proposed four elementary reactions for the global mechanism. We analyzed the adsorption of sarin on the brucite layer through the fluorine and the phosphonyl oxygen atoms (P=O). The two transition states correspond to a hydroxyl anion motion toward the phosphorus atom and to a fluoride moving toward the hydroxyl vacant position; the activation barrier for the rate-limiting step, corresponds to adsorbed sarin attacked by the brucite hydroxyl. The products of the global reaction were an isopropyl methylphosphonate molecule and [Mg(OH) 2−x ]F x . The results of the deactivation process of sarin using a brucite surface show the potential of layered hydroxides to degrade OP compounds. Also the results of this resea...

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Section: Degradação Do Agente Neurotóxico Vx Por óXido De Magnésiounclassified

Theoretical Chemistry at the Service of the Chemical Defense: Degradation of Nerve Agents in Magnesium Oxide and Hydroxide Surface

Alvim¹,

Vaiss²,

Leitão³

et al. 2014

Revista Virtual De Química

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“…Therefore, there is a need to develop efficient reactivators for the OP-inhibited AChE. Computational methods offer an ability to explore these types of reactions [3,[12][13][14][15][16][17][18][19][20][21][22][23][24] while avoiding exposure to these deadly agents. Hence, it is quite useful in suggesting new nucleophiles with greater efficiency for the reactivation of inhibited AChE.…”

Section: Introductionmentioning

confidence: 99%

Probing the reactivation process of sarin-inhibited acetylcholinesterase with α-nucleophiles: Hydroxylamine anion is predicted to be a better antidote with DFT calculations

Khan

Bandyopadhyay

et al. 2011

Journal of Molecular Graphics and Modelling

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“…Computational methods offer a way to discover such reactions [3,[12][13][14][15][16][17][18][19][20][21][22][23][24] while avoiding exposure to these deadly agents, and are thus very useful for proposing new nucleophiles with superior efficiency for inhibited AChE reactivation. Computational methods offer a way to discover such reactions [3,[12][13][14][15][16][17][18][19][20][21][22][23][24] while avoiding exposure to these deadly agents, and are thus very useful for proposing new nucleophiles with superior efficiency for inhibited AChE reactivation.…”

Section: Introductionmentioning

confidence: 99%

Assessing the reactivation efficacy of hydroxylamine anion towards VX-inhibited AChE: a computational study

Khan

Ganguly

2011

J Mol Model

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Oximate anions are used as potential reactivating agents for OP-inhibited AChE because of they possess enhanced nucleophilic reactivity due to the α-effect. We have demonstrated the process of reactivating the VX-AChE adduct with formoximate and hydroxylamine anions by applying the DFT approach at the B3LYP/6-311 G(d,p) level of theory. The calculated results suggest that the hydroxylamine anion is more efficient than the formoximate anion at reactivating VX-inhibited AChE. The reaction of formoximate anion and the VX-AChE adduct is a three-step process, while the reaction of hydroxylamine anion with the VX-AChE adduct seems to be a two-step process. The rate-determining step in the process is the initial attack on the VX of the VX-AChE adduct by the nucleophile. The subsequent steps are exergonic in nature. The potential energy surface (PES) for the reaction of the VX-AChE adduct with hydroxylamine anion reveals that the reactivation process is facilitated by the lower free energy of activation (by a factor of 1.7 kcal mol(-1)) than that of the formoximate anion at the B3LYP/6-311 G(d,p) level of theory. The higher free energy of activation for the reverse reactivation reaction between hydroxylamine anion and the VX-serine adduct further suggests that the hydroxylamine anion is a very good antidote agent for the reactivation process. The activation barriers calculated in solvent using the polarizable continuum model (PCM) for the reactivation of the VX-AChE adduct with hydroxylamine anion were also found to be low. The calculated results suggest that V-series compounds can be more toxic than G-series compounds, which is in accord with earlier experimental observations.

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Ab Initio Molecular Orbital and Density Functional Studies on the Solvolysis of Sarin and O,S-Dimethyl Methylphosphonothiolate, a VX-like Compound

Cited by 75 publications

References 76 publications

Theoretical Chemistry at the Service of the Chemical Defense: Degradation of Nerve Agents in Magnesium Oxide and Hydroxide Surface

Theoretical Chemistry at the Service of the Chemical Defense: Degradation of Nerve Agents in Magnesium Oxide and Hydroxide Surface

Probing the reactivation process of sarin-inhibited acetylcholinesterase with α-nucleophiles: Hydroxylamine anion is predicted to be a better antidote with DFT calculations

Assessing the reactivation efficacy of hydroxylamine anion towards VX-inhibited AChE: a computational study

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