Livesay Brooke N, Schmidt Jurgen G, Williams Robert F, Billow Brennan S, Tondreau Aaron M
Los Alamos National Laboratory, Los Alamos, New Mexico 87544, United States.
ACS Org Inorg Au. 2023 May 25;3(4):199-208. doi: 10.1021/acsorginorgau.3c00003. eCollection 2023 Aug 2.
Organophosphorus nerve agents (OPAs) are a toxic class of synthetic compounds that cause adverse effects with many biological systems. Development of methods for environmental remediation and passivation has been ongoing for years. However, little progress has been made in therapeutic development for exposure victims. Given the postexposure behavior of OPA materials in enzymes such as acetylcholinesterase (AChE), development of electrophilic compounds as therapeutics may be more beneficial than the currently employed nucleophilic countermeasures. In this report, we present our studies with an electrophilic, 16-electron manganese complex (PNP)Mn(CO) () and the nucleophilic hydroxide derivative (PNP)Mn(CO)(OH) (). The reactivity of with phosphorus acids and the reactivity of with the P-F bond of diisopropylfluorophosphate (DIPF) were studied. The role of water in both nucleophilic and electrophilic reactivity was investigated with the use of O-labeled water. Promising results arising from reactions of both and with organophosphorus substrates are reported.
有机磷神经毒剂(OPAs)是一类有毒的合成化合物,会对许多生物系统产生不利影响。环境修复和钝化方法的开发已经进行了多年。然而,针对暴露受害者的治疗开发进展甚微。鉴于OPA材料在乙酰胆碱酯酶(AChE)等酶中的暴露后行为,开发亲电化合物作为治疗剂可能比目前使用的亲核对策更有益。在本报告中,我们展示了我们对亲电的16电子锰配合物(PNP)Mn(CO)()和亲核氢氧化物衍生物(PNP)Mn(CO)(OH)()的研究。研究了与磷酸的反应活性以及与二异丙基氟磷酸酯(DIPF)的P-F键的反应活性。使用O标记的水研究了水在亲核和亲电反应活性中的作用。报告了与有机磷底物反应产生的有前景的结果。