Organophosphate Scavengers

bw

In a collaboration with the Institute of Pharmacology and Toxicology of the German Armed Forces, new antidotes are developed that mediate the decomposition of neurotoxic organophosphates and organophosphonates. In this context, cyclodextrin derivatives were initially tested as possible scavengers. The following cyclodextrin derivative was shown to allow detoxification of cyclosarin within a few seconds.1 This compound is so active that it even protects guinea pigs from poisoning with cyclosarin when given prophylactically in sufficient doses.2

cyclodextrin

Cyclodextrin derivatives have also been identified for the detoxification of tabun.3

For the detoxification of persistent V-type nerve agents, which are predominantly protonated and therefore cationic at physiological pH due to an amino group in one of the side chains, cation-binding receptors were tested as potential scavengers. In this context, the calix[4]arene derivative shown below was developed, which is the first low molecular weight scavenger to detoxify VX and other V-type nerve agents within a few minutes.4 This activity is still too low for an in vivo use and current work therefore pursues the synthesis of more active derivatives.

calixaren

References

  1. M. Zengerle, F. Brandhuber, C. Schneider, F. Worek, G. Reiter, S. Kubik Beilstein J. Org. Chem. 2011, 7, 1543-1554.
  2. F. Worek, T. Seeger, M. Zengerle, S. Kubik, H. Thiermann, T. Wille Toxicol. Lett. 2014, 224, 222-227.
  3. F. Brandhuber, M. Zengerle, L. Porwol, A. Bierwisch, M. Koller, G. Reiter, F. Worek, S. Kubik Chem. Commun. 2013, 49, 3425-3427.
  4. C. Schneider, A. Bierwisch, M. Koller, F. Worek, S. Kubik Angew. Chem. 2016, 128, 12859-12863; Angew. Chem. Int. Ed. 2016, 55, 12668-12672.