Sulfonatocalix[4]arene‐Based Scavengers for V‐Type Nerve Agents with Enhanced Detoxification Activity

Synthetic small molecule scavengers that rapidly detoxify nerve agents in vivo allow (pre)treatment of nerve agent poisoning. However, scavengers that detoxify persistent V-type nerve agents at pH 7.4 and 37 °C with sufficient efficiency are still unknown. The most promising compound to date is a monosubstituted sulfonatocalix[4]arene containing a hydroxamic acid group. This compound was used to investigate the effect of structural modifications on detoxification activity. While none of the monosubstituted calixarene derivatives considered in this context possessed higher activity than the parent compound, the disubstituted derivatives were very active, exhibiting half-lives of detoxification under the conditions of an established in vitro assay of <1.5 min. The rate of detoxification decreased with decreasing scavenger concentration, but even at a fourfold molar excess of the scavenger, complete detoxification of 2.5 μM solutions of some nerve agents could be achieved within one hour. These disubstituted calixarene derivatives thus bring synthetic scavengers for V-type nerve agents closer to application.