Evaluation of the possibility of binary synthesis of VX by theoretical calculation

[Display omitted] •Proposal of a new evaluation method to treat extremely dangerous substances safely.•Theoretical calculations of reaction pathways of VX synthesis.•Extremely dangerous reactions could be examined safely by theoretical calculations.•Binary synthesis at ambient temperature is not likely under the examined conditions. In 2017, an assassination using VX occurred in Malaysia, in which some experts believe that VX was synthesized onsite by mixing two starting materials (so-called binary synthesis). From a social security perspective, investigation of whether binary synthesis of VX is feasible under ambient conditions is urgently required. Considering the extreme toxicity of VX, we made use of DFT calculations. We chose four reaction conditions including the SN2 reactions and the ring opening reaction and calculated the reaction pathways of VX synthesis and hydrolysis of starting materials. This paper demonstrates the usefulness of theoretical calculations in researching highly toxic substances safely.