Human Protection and Performance Division, Defence Science and Technology Organisation, 506 Lorimer St., Fishermans Bend, Victoria 3207, Australia.
J Org Chem. 2009 Dec 18;74(24):9319-27. doi: 10.1021/jo901944p.
The alkaline perhydrolysis of the nerve agent O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) was investigated by studying the ion-molecule reactions of HOO(-) with O,S-dimethyl methylphosphonothioate in a modified linear ion-trap mass spectrometer. In addition to simple proton transfer, two other abundant product ions are observed at m/z 125 and 109 corresponding to the S-methyl methylphosphonothioate and methyl methylphosphonate anions, respectively. The structure of these product ions is demonstrated by a combination of collision-induced dissociation and isotope-labeling experiments that also provide evidence for their formation by nucleophilic reaction pathways, namely, (i) S(N)2 at carbon to yield the S-methyl methylphosphonothioate anion and (ii) nucleophilic addition at phosphorus affording a reactive pentavalent intermediate that readily undergoes internal sulfur oxidation and concomitant elimination of CH(3)SOH to yield the methyl methylphosphonate anion. Consistent with previous solution phase observations of VX perhydrolysis, the toxic P-O cleavage product is not observed in this VX model system and theoretical calculations identify P-O cleavage to be energetically uncompetitive. Conversely, intramolecular sulfur oxidation is calculated to be extremely exothermic and kinetically accessible explaining its competitiveness with the facile gas phase proton transfer process. Elimination of a sulfur moiety deactivates the nerve agent VX and thus the intramolecular sulfur oxidation process reported here is also able to explain the selective perhydrolysis of the nerve agent to relatively nontoxic products.
我们在改良的线性离子阱质谱仪中研究了 HOO(-)与 O,S-二甲基甲基膦酸硫酯的离子-分子反应，从而研究了神经毒剂 O-乙基 S-[2-(二异丙基氨基)乙基]甲基膦酸硫酯(VX)的堿性过水解。除了简单的质子转移外，还观察到另外两个丰度较高的产物离子，其质荷比分别为 m/z 125 和 109，分别对应 S-甲基甲基膦酸硫酯和甲基甲基膦酸根阴离子。通过碰撞诱导解离和同位素标记实验的组合，证明了这些产物离子的结构，这些实验还提供了证据表明它们是通过亲核反应途径形成的，即(i)在碳上进行 S(N)2 反应生成 S-甲基甲基膦酸硫酯阴离子，和(ii)磷上的亲核加成生成反应性五价中间体，该中间体容易发生内部硫氧化，同时消除 CH(3)SOH，生成甲基甲基膦酸根阴离子。与 VX 过水解的先前溶液相观察结果一致，在该 VX 模型系统中未观察到有毒的 P-O 断裂产物，并且理论计算表明 P-O 断裂在能量上是没有竞争力的。相反，计算出分子内硫氧化是非常放热的，并且动力学上是可接近的，这解释了它与容易发生的气相质子转移过程的竞争力。硫部分的消除使神经毒剂 VX 失活，因此，这里报道的分子内硫氧化过程也能够解释神经毒剂选择性地过水解为相对无毒的产物。
