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, λ₁=284 nm and λ₂=353 nm. The peak at λ₂=353 nm is representative for the amount of zwitterionic obidoxime, i.e. the active form of obidoxime. By addition of sarin, λ₁ shifts immediately to 278 nm and the intensity at λ₂ decreases, thus indicating an interaction. TLC and³¹P-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 t_1/2=13.3 min at 24°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.