Drug discovery is an expensive and time-consuming process. To make this process more efficient quantum chemistry methods can be employed. The electrophilicity index is one property that can be calculated by quantum chemistry methods, and if calculated correctly gives insight into the reactivity of covalent inhibitors. Herein we present the usage of the electrophilicity index on three common warheads, i.e., acrylamides, 2-chloroacetamides, and propargylamides. We thoroughly examine the properties of the electrophilicity index, show which pitfalls should be avoided, and what the requirements to successfully apply the electrophilicity index are.

中文翻译：

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通过亲电指数预测共价抑制剂反应性——范围内和范围外

药物发现是一个昂贵且耗时的过程。为了使这个过程更有效，可以采用量子化学方法。亲电指数是一种可以通过量子化学方法计算的属性，如果计算正确，可以深入了解共价抑制剂的反应性。在此，我们介绍了亲电指数在三种常见弹头上的使用，即丙烯酰胺、2-氯乙酰胺和炔丙酰胺。我们彻底检查了亲电性指数的特性，展示了应该避免哪些陷阱，以及成功应用亲电性指数的要求是什么。