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 Systems
CBRN - CBRN Protection
TS - Technical Sciences
Chemistry
Covalent conjugate
Detoxification
Organophosphorus compound
Supramolecular scavenger
β-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