Oxidative Detoxification of Sulfur-Containing Chemical Warfare Agents by Electrophilic Iodine

Abstract

Mild oxidation of sulfur-containing chemical warfare agents was performed in organic medium by electrophilic iodine reagents. Kinetic experiments on sulfur mustard (HD) showed rapid (t 1/2 < 3 min) and selective oxidation to the nonvesicant sulfoxide product (HD-SO) in acetonitrile or propylene carbonate solutions (9% water added) containing excess N-iodosuccinimide (NIS). Molecular iodine solutions in these solvents led to similar results as with NIS but at much slower rates (t 1/2 ∼ 90 min). Higher donor number solvents, such as THF, DMF, or DMSO, showed slower rates with both iodine and NIS. The oxidation of the nerve agent O-ethyl-S-2-(N,N-diisopropylaminoethyl)­methyl­phos­phono­thioate (VX) selectively to the nontoxic ethyl methylphosphonic acid product exhibited fast rates (t 1/2 = 6 min) using NIS in DMSO solution. In all other solvents tested with VX, rates were slower (t 1/2 ∼ 30–70 min). Oxidation experiments under the same conditions with chloroethyl ethyl sulfide (HD simulant) and O,S-diethyl methylphosphonothioate (VX simulant) led to much faster reaction rates. These transformations are believed to proceed through electrophilic iodine attack on the sulfur moiety and display solvent dependency based on the agents’ structural and chemical properties.

Structural elucidation of V‐type nerve agents by liquid chromatography/electrospray ionization mass spectrometry

“…Neither the alkyl group on the oxygen (R 2 ) nor the alkyl group on the phosphorous atom (R 1 ) in these compounds contributed notably to the spectrum, and it was difficult to determine the structure of the phosphonate group. For the structural elucidation of the phosphonate group, we employed NIS, which induced the hydrolysis of the V‐nerve agents into their corresponding phosphonic acids 12 …”

“…Therefore, the development of a selective method for the quantitative degradation of V‐agents to their corresponding alkyl alkylphosphonic acids is highly desirable. Smolkin et al 12 recently developed a mild and selective oxidation of VX nerve agent to nontoxic EMPA with a fast reaction rate ( t 1/2 = 6 min) using an excess of an electrophilic iodine reagent (NIS, 11 equiv) in a DMSO/H 2 O (10:1).…”

“…We evaluated NIS in both MeOH/H 2 O and DMSO/H 2 O solutions under the reaction conditions described by Smolkin et al 12 with minor modifications. Excess NIS (1 mg/mL) was employed to solely and rapidly produce the alkyl alkylphosphonic acid hydrolysis products (cleavage of the P–S bond) without forming DES‐VX (cleavage of the P–O bond).…”

“…For the structural elucidation of the phosphonate group, we employed NIS, which induced the hydrolysis of the V-nerve agents into their corresponding phosphonic acids. 12…”

A novel approach for the detection and identification of sulfur mustard using liquid chromatography–electrospray ionization–tandem mass spectrometry based on its selective oxidation to sulfur mustard monoxide with N‐iodosuccinimide

“…Oxidation is one of the most important approaches for sulfur‐containing chemical warfare agent (CWA) detoxification, of which a variety of oxidants are available for use 32,33 . Inspired by this chemistry, we sought to use a selective oxidizing agent that converts HD into HDSO, thereby preserving the identity of the HD skeleton, allowing its unambiguous identification via LC‐ESI‐MS/MS analysis.…”