Interaction of obidoxime with sarin in aqueous solution.
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.
Waser
P G
PG
Department of Pharmacology, Zürich, Switzerland.
Alioth-Streichenberg
C M
CM
Hopff
W H
WH
Portmann
R
R
Hofmann
W
W
Niederhauser
A
A
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
D012996:Solutions; D010758:Phosphorus; D009768:Obidoxime Chloride; D012524:Sarin