Role of the P–F Bond in Fluoride-Promoted Aqueous VX Hydrolysis: An Experimental and Theoretical Study

Abstract

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.

Component Mobility by a Minute Quantity of the Appropriate Solvent as a Principal Motif in the Acceleration of Solid-Supported Reactions

“…On the basis of the fact that the fluoride ion is the first nucleophile acting in the OP compound hydrolysis, forming a fluoridate intermediate that is immediately hydrolyzed in basic aqueous environment, 54 it is reasonable to assume that the role of water as a solvent is more significant than its action in attacking this intermediate. This issue will be broadly discussed later.…”

“…Concurrently, we reported on fluoride-promoted homogeneous VX (O-ethyl S-2-(diisopropylamino)ethylmethylphosphonothioate) hydrolysis in dilute aqueous solutions. 54 In these reactions, the corresponding fluoridate (obtained from thiol group displacement by a fluoride ion) was initially formed as an intermediate and then quickly hydrolyzed to the appropriate phosphonic acid. Once the pH was maintained at its initial level (10.5) using a buffer, hydrolysis of the fluoridate intermediate to the phosphonate salt product was so fast that it could not be observed.…”

A theoretical study of the hydrolysis mechanism of A-234; the suspected novichok agent in the Skripal attack

“…When the water molecule is on the same side of the leaving group, a frontside S N 2 mechanism occurs; when the water molecule is on the opposite side of the leaving group, an addition-elimination reaction occurs. 4,[39][40][41][42] 3.2.1 Frontside attack. In the frontside S N 2 mechanism, the water molecule approaches the electropositive phosphorus from the same side as the leaving group.…”

Solvent Effects on the Reactions of the Nerve Agent VX with KF/Al2O3: Heterogeneous or Homogeneous Decontamination?

“…The fact that VX hydrolysis in an aqueous fluoride solution is much faster than that of DEMPT provided support for that reasoning. 19 As shown in Table 1, although dry KF/Al 2 O 3 presents totally different conditions than an aqueous solution, a similar trend was observed. Namely, the VX reaction was found to be much faster than that of DEMPT (entry 1, t 1/2 of 6.2 vs 433 h 18 ).…”