Waser P G, Alioth-Streichenberg C M, Hopff W H, Portmann R, Hofmann W, Niederhauser A
Department of Pharmacology, Zürich, Switzerland.
Arch Toxicol. 1992;66(3):211-5. doi: 10.1007/BF01974017.
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.
通过不同的分析方法显示了氯解磷定（双复磷）与沙林的相互作用。在pH 7.4条件下，氯解磷定的紫外光谱产生两个吸收最大值，λ1 = 284 nm和λ2 = 353 nm。λ2 = 353 nm处的峰代表两性离子型氯解磷定的量，即氯解磷定的活性形式。加入沙林后，λ1立即移至278 nm，λ2处的强度降低，从而表明存在相互作用。薄层色谱法和31P - 核磁共振证据表明，单膦酰化和双膦酰化的氯解磷定都存在。在24℃下，在pH 7.4的MOPS（3 - [N - 吗啉代]丙烷磺酸）缓冲的D2O中，膦酰化氯解磷定的分解半衰期为13.3分钟。双膦酰化氯解磷定的分解更快。有人认为双膦酰化氯解磷定的分解是通过单膦酰化形式进行的。单膦酰化和双膦酰化氯解磷定的形成和分解都依赖于pH值。我们得出结论，氯解磷定通过捕获游离的沙林分子发挥解毒作用，从而增加其极性。由此，沙林通过血脑屏障的转运受到限制，其经肾排泄得到促进。
