73207-98-4Relevant articles and documents
Influence of cyclic and acyclic cucurbiturils on the degradation pathways of the chemical warfare agent VX
Andrae, Beatrice,Bauer, Daniel,Ga?, Patrick,Koller, Marianne,Kubik, Stefan,Worek, Franz
supporting information, p. 5218 - 5227 (2020/07/23)
The highly toxic nerve agent VX is a methylphosphonothioate that degrades via three pathways in aqueous solution, namely through the hydrolysis of the P-O or P-S bonds, or the cleavage of the C-S bond at the 2-aminoethyl residue. In the latter case, an aziridinium ion and a phosphonothioate is formed. Here it is shown that acyclic or cyclic cucurbiturils inhibit these reactions in phosphate buffer at physiological pH and thus stabilise the nerve agent. When using unbuffered basic solutions as the reaction medium, however, in which the P-S or P-O bonds are normally hydrolysed preferentially, cucurbiturils turned out to strongly shift VX degradation towards the cleavage of the C-S bond. Cucurbit[7]uril, in particular, has a so pronounced effect under suitable conditions that it almost completely suppresses the formation of products resulting from the other degradation pathways. Investigations involving VX analogues in combination with computational methods suggest that one reason for the reaction control exerted by the cucurbiturils is the preorganisation of VX for aziridinium ion formation. In addition, cucurbit[7]uril also lowers the transition state of the reaction by stabilising the positive charge developing on the way to the product. Cucurbiturils thus have a marked effect on the reactivity of a highly toxic nerve agent, which potentially allows using them for decontamination purposes. This journal is
Pathways for the Reactions Between Neurotoxic Organophosphorus Compounds and Oximes or Hydroxamic Acids
Bierwisch, Anne,Koller, Marianne,Worek, Franz,Kubik, Stefan
supporting information, p. 5831 - 5838 (2016/12/18)
To obtain mechanistic insight into the recently demonstrated detoxification ability of β-cyclodextrin derivatives containing substituents with oxime or hydroxamic acid residues, analogous glucose derivatives with the same substituents were treated with cyclosarin (GF), tabun (GA), and O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) in (Tris)-HCl buffer (0.1 m, pH 7.40), and the different reaction pathways were studied by31P NMR spectroscopy and mass spectrometry. Consistent with previous reports, the oxime is phosphonylated by GF, which is followed by elimination of O-cyclohexyl methylphosphonate to afford a nitrile. Reaction of the hydroxamic acid with GA depends on whether the nitrogen atom of the hydroxamic acid bears a substituent or not. The unsubstituted hydroxamic acid affords a stable phosphate ester lacking the cyanide and the dimethylamino group of GA. If the hydroxamic acid is methylated, the initially formed phosphorylated product undergoes a number of transformations, including cleavage of the C–N bond of the hydroxamic acid. Reaction of the hydroxamic acid with VX involves a Lossen rearrangement. These investigations thus show that all investigated nucleophiles are irreversibly modified upon reaction with nerve agents under the chosen conditions, which indicates that cyclodextrins with oximes or hydroxamic acid as substituents are unlikely to afford catalytic nerve-agent scavengers.
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
supporting information, p. 10042 - 10049 (2013/01/15)
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.
