The enantiomers of racemic 2-hydroxyimino-N-(azidophenylpropyl)acetamide-derived triple-binding oxime reactivators were separated, and tested for inhibition and reactivation of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibited with tabun (GA), cyclosarin (GF), sarin (GB), and VX. Both enzymes showed the greatest affinity toward the methylimidazole derivative (III) of 2-hydroxyimino-N-(azidophenylpropyl)acetamide (I). The crystal structure was determined for the complex of oxime III within human BChE, confirming that all three binding groups interacted with active site residues. In the case of BChE inhibited by GF, oximes I (kr = 207 M-1 min-1) and III (kr = 213 M-1 min-1) showed better reactivation efficiency than the reference oxime 2-PAM. Finally, the key mechanistic steps in the reactivation of GF-inhibited BChE with oxime III were modeled using the PM7R6 method, stressing the importance of proton transfer from Nε of His438 to Oγ of Ser203 for achieving successful reactivation.

中文翻译：

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对映体分离，体外测试和有机磷酸酶抑制胆碱酯酶的三重结合活化剂的结构表征。

分离由外消旋2-羟基亚氨基-N-（叠氮苯丙基）乙酰胺衍生的三结合肟活化剂的对映异构体，并测试抑制和再活化被塔邦（GA），环沙蛋白（GF）抑制的乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE） ），沙林（GB）和VX。两种酶对2-羟基亚氨基-N-（叠氮苯基丙基）乙酰胺（I）的甲基咪唑衍生物（III）显示出最大的亲和力。确定了人BChE中肟III的配合物的晶体结构，证实了所有三个结合基团均与活性位点残基相互作用。在GF抑制BChE的情况下，肟I（kr = 207 M-1 min-1）和III（kr = 213 M-1 min-1）比参考肟2-PAM表现出更好的再活化效率。最后，