title: Interaction of obidoxime with sarin in aqueous solution.
abstract: The interaction of obidoxime (Toxogonin) with sarin was shown by different analytical methods. The UV spectrum of obidoxime at pH 7.4 yields two absorption maxima, lambda 1 = 284 nm and lambda 2 = 353 nm. The peak at lambda 2 = 353 nm is representative for the amount of zwitter-ionic obidoxime, i.e. the active form of obidoxime. By addition of sarin, lambda 1 shifts immediately to 278 nm and the intensity at lambda 2 decreases, thus indicating an interaction. TLC and 31P-NMR evidence shows that both mono-phosphonylated and diphosphonylated obidoximes are present. Decomposition of phosphonylated obidoxime in MOPS (3-[N-morpholino] propanesulfonic acid) buffered D2O at pH 7.4 occurs with t1/2 = 13.3 min at 24 degrees C. Decomposition of di-phosphonylated obidoxime is faster. It is suggested that decomposition of di-phosphonylated obidoxime occurs through the mono-phosphonylated form. Formation and decomposition of mono- and di-phosphonylated obidoxime is pH dependent. We conclude that obidoxime exerts a detoxifying effect by capturing free sarin molecules and thus increasing its polarity. Thereby the transition of sarin through the blood-brain barrier is restricted and its renal elimination facilitated.
authors.affiliation: Department of Pharmacology, Zürich, Switzerland.
authors.forename: P G
authors.initials: PG
authors.lastname: Waser
authors.forename: C M
authors.initials: CM
authors.lastname: Alioth-Streichenberg
authors.forename: W H
authors.initials: WH
authors.lastname: Hopff
authors.forename: R
authors.initials: R
authors.lastname: Portmann
authors.forename: W
authors.initials: W
authors.lastname: Hofmann
authors.forename: A
authors.initials: A
authors.lastname: Niederhauser
mesh_terms: D002855:Chromatography, Thin Layer; D004347:Drug Interactions; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009768:Obidoxime Chloride / Q000737:chemistry*; D010758:Phosphorus; D012524:Sarin / Q000737:chemistry*; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet
chemical_list: D012996:Solutions; D010758:Phosphorus; D009768:Obidoxime Chloride; D012524:Sarin