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Detoxification of tabun at physiological pH mediated by substituted β-cyclodextrin and glucose derivatives containing oxime groups
- Source :
- Toxicology. 302:163-171
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- The ability of 13 β-cyclodextrin and 2 glucose derivatives containing substituents with oxime groups as nucleophilic components to accelerate the degradation of tabun at physiological pH has been evaluated. To this end, a qualitative and a quantitative enzymatic assay as well as a highly sensitive enantioselective GC–MS assay were used. In addition, an assay was developed that provided information about the mode of action of the investigated compounds. The results show that attachment of pyridinium-derived substituents with an aldoxime group in 3- or 4-position to a β-cyclodextrin ring affords active compounds mediating tabun degradation. Activities differ depending on the structure, the number, and the position of the substituent on the ring. Highest activity was observed for a β-cyclodextrin containing a 4-formylpyridinium oxime residue in 6-position of one glucose subunit, which detoxifies tabun with a half-time of 10.2 min. Comparison of the activity of this compound with that of an analog in which the cyclodextrin ring was replaced by a glucose residue demonstrated that the cyclodextrin is not necessary for activity but certainly beneficial. Finally, the results provide evidence that the mode of action of the cyclodextrin involves covalent modification of its oxime group rendering the scavenger inactive after reaction with the first tabun molecule.
- Subjects :
- Obidoxime Chloride
Stereochemistry
Substituent
Pyridinium Compounds
Toxicology
Gas Chromatography-Mass Spectrometry
Residue (chemistry)
chemistry.chemical_compound
Nucleophile
Oximes
Humans
Chemical Warfare Agents
Tabun
chemistry.chemical_classification
Molecular Structure
Cyclodextrin
beta-Cyclodextrins
Enantioselective synthesis
Hydrogen-Ion Concentration
Oxime
Organophosphates
Glucose
chemistry
Inactivation, Metabolic
Cholinesterase Inhibitors
Enantiomer
Subjects
Details
- ISSN :
- 0300483X
- Volume :
- 302
- Database :
- OpenAIRE
- Journal :
- Toxicology
- Accession number :
- edsair.doi.dedup.....1cce2fd03f355583df2ebe181efe2b2a