Detoxifying VX

Venomous Agent X (VX) and related organophosphonate nerve agents do their deadly work by deactivating the enzyme acetylcholinesterase. This causes the neurotransmitter acetylcholine to build up, poisoning the central and peripheral nervous systems. Doctors currently treat exposure to these nerve agents by managing the symptoms of acetylcholine accumulation. But there is a window of several hours between exposure to VX and the time its toxic effects take hold in which a therapy might be used to detoxify the organophosphate before it reaches its target. Working toward that goal, a team led by Stefan Kubik of the Kaiserslautern University of Technology developed sulfonatocalix[4]arenes substituted with a hydroxamic acid group (shown) that can deactivate VX and related compounds in three to five minutes under mild conditions (Angew. Chem, Int. Ed. 2016, DOI: 10.1002/anie.201606881). The positively charged organophosphonate slips into the negatively charged calixarene, where it is deactivated via reaction with the hydroxamic acid. The reaction is stoichiometric, which makes it less attractive than catalytic biological scavengers currently under development. But Kubik believes the calixarenes are a promising lead toward synthetic compounds that can scavenge VX and similar nerve agents.