The manufacture and use of single- or enriched-enantiomer pesticides are green-chemistry developments advocated in the 21st century, but predictive work for chiral switch of newly produced chiral active ingredients is limited. In the present study, the stereoselective separation, target activity, and nontarget toxicity of O,S-dimethyl-N-(2,2,2-trichloro-1-methoxyethyl)phosphoramidothioate (MCP), a new organophosphorus compound, were investigated. Because being highly active and safe is a prerequisite for marketing single-isomer products, the above studies were used to offer some implications for the chiral switch of racemic MCP. The results showed that all four stereoisomers of MCP were successfully separated with a Chiralpak AD column on HPLC. The resolved isomers and the pairs of enantiomers were further distinguished using a circular dichroism detector, designating the first and third eluted peaks as one pair of enantiomers and the second and fourth peaks as the other pair. Then, the insecticidal activities and acute and delayed toxicities of the resolved isomers of MCP were evaluated by their acute lethal efficacy against Daphina magna, their inhibitory potentials to acetylcholinesterase (AChE), and axon-like outgrowth of the SH-SY5Y cells, respectively. The inhibition potencies of the isomers against AChE in SH-SY5Y cells were low and slightly stereoselective. On the other hand, a significant difference was observed among the isomers in their activities and delayed neurotoxicities. The 48 h acute toxicities of isomers to D. magna followed the order peak 1 ≈ pair 1 (i.e., equimolar mixture of peaks 1 and 3) > peak 4 ≈ racemate > pair 2 (i.e., equimolar mixture of peaks 2 and 4) > peak 2 > peak 3, with 1.0−6.3-fold differences among them. In comparison, the inhibitory potentials of the isomers toward axon growth of SH-SY5Y cells decreased in the order peak 2 > pair 2 > peak 4 > racemate > peak 3 > pair 1 ≈ peak 1, with at least a 60-fold difference between the strongest and weakest inhibitors. Those results imply that peak 1 has the optimal target selectivity and ecological profile among the four stereoisomers. It was calculated that two-thirds of the usual pesticide usage can be saved concomitantly with a substantial decrease in neuropathic risk if MCP is present only as peak 1 rather than the racemate. When considering the absence of the economically feasible synthetic methods and techniques to produce optically pure isomers of organophosphorus pesticides, pair 1 of MCP shows considerable worth for future applications on the basis of its biological predominance and cost effectiveness.

中文翻译：

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新型有机磷化合物O，S-二甲基-N-（2,2,2-三氯-1-甲氧基乙基）磷酰胺基硫代酸酯的立体异构体分离和生物测定：对手性转换的一些启示。

单一或富集对映体农药的制造和使用是21世纪倡导的绿色化学发展，但是对新生产的手性活性成分进行手性转换的预测工作有限。在本研究中，O，S-二甲基-N的立体选择性分离，目标活性和非目标毒性研究了一种新的有机磷化合物-（2,2,2-三氯-1-甲氧基乙基）磷酰氨基硫代酸酯（MCP）。由于高活性和安全性是销售单一异构体产品的前提，因此上述研究用于为外消旋MCP的手性转换提供一些启示。结果表明，在HPLC上用Chiralpak AD色谱柱成功分离了MCP的所有四种立体异构体。使用圆二色性检测器进一步区分分辨出的异构体和对映体对，将第一和第三洗脱峰指定为一对对映体，将第二和第四峰指定为另一对。然后，MCP的解决异构体的杀虫活性和急性的和滞后的毒性是由他们的急性致死打击效果评估大型蚤，它们分别对SH-SY5Y细胞的乙酰胆碱酯酶（AChE）和轴突样生长的抑制潜能。异构体对SH-SY5Y细胞中AChE的抑制能力很低，并且具有立体选择性。另一方面，观察到异构体的活性和延迟的神经毒性之间存在显着差异。异构体对D. magna的48小时急性毒性遵循峰1≈对1（即峰1和3的等摩尔混合物）>峰4≈外消旋体>对2（即峰2和4的等摩尔混合物）>峰2>峰3的顺序，其中1.0-6.3-折叠它们之间的差异。相比之下，异构体对SH-SY5Y细胞轴突生长的抑制潜力按峰2>对2>峰4>外消旋体>峰3>对1≈峰1的顺序降低，两者之间至少有60倍的差异最强和最弱的抑制剂。这些结果表明，在四种立体异构体中，峰1具有最佳的目标选择性和生态特征。据计算，如果MCP仅以峰1而不是外消旋体存在，则可以节省三分之二的常用农药，同时大大降低了神经病变的风险。