Print Email Facebook Twitter Elimination kinetics and molecular reaction mechanisms of cyclosarin (GF) by an oxime substituted β-cyclodextrin derivative in vitro Title Elimination kinetics and molecular reaction mechanisms of cyclosarin (GF) by an oxime substituted β-cyclodextrin derivative in vitro Author Kranawetvogl, A. Müller, S. Kubik, S. Spruit, W.E.T. Thiermann, H. Worek, F. Noort, D. Reiter, G. Publication year 2015 Abstract Detoxification mechanisms of the chemical warfare agent cyclosarin (GF) in presence of 6-OxP-CD were investigated in detail in in vitro model systems. Most important finding was the preference of 6-Ox-P-CD to eliminate the more toxic (-)-GF. However, elimination of GF enantiomers was dependent on the 6-OxP-CD:GF ratios showing decreasing stereoselectivity and speed of the reaction with increasing GF concentrations. Formation of covalent mono, bis, tris and tetrakis conjugates ((CHMP)n-6-OxP-CD) and appearance of small molecular fragments (SMF) as possible decomposition products after consumption of 6-OxP-CD could be observed.. Interestingly, the non-toxic metabolite O-cyclohexyl methylphosphonic acid (CHMPA) and covalent mono and bis conjugates of 6-OxP-CD and GF were immediately formed, indicating that GF elimination proceeds along different pathways. These important new insights provide information about the mode of action of 6-Ox-P-CD including the role of the pyridinium aldoxime group on the cyclodextrin ring. They are the basis for further investigations in biological media, which could eventually lead to approval of 6-OxP-CD as a new antidote against nerve agent toxicity. © 2015 Elsevier Ireland Ltd. Subject Observation, Weapon & Protection SystemsCBRN - CBRN ProtectionTS - Technical SciencesChemistryCovalent conjugateDetoxificationOrganophosphorus compoundSupramolecular scavengerβ-cyclodextrin To reference this document use: http://resolver.tudelft.nl/uuid:1294ede9-ec56-4ad5-b594-dbb1679961ca DOI https://doi.org/10.1016/j.toxlet.2015.08.007 TNO identifier 528228 Publisher Elsevier Ireland Ltd ISSN 0378-4274 Source Toxicology Letters, 239 (1), 41-52 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.