Background: Aripiprazole is a quinolinone derivative. It shows a high affinity for neurotransmitters dopamine and serotonin receptors, which can overcome the blood-brain barrier (BBB) to reach the central nervous system (CNS) to exert therapeutic effects. Its radioiodination may lead to high radiochemical yield and improved its affinity. Aripiprazole radioiodination is an aromatic electrophilic substitution.

Objective: Herein, we investigate the favorable atom site of the aromatic electrophilic substitution of aripiprazole by calculating the Fukui indices of heavy atoms and ESP charges of the parent molecule.

Methods: The calculations have been carried out at the B3LYP/LanL2DZ level of theory. The iodinated aripiprazole structure is confirmed by comparing the experimental and the predicted 1H NMR chemical shifts of the parent molecule and its iodinated forms.

Results: Finally, the electronic properties of aripiprazole and its iodinated form were calculated at the same level of theory. Nucleophilic Fukui indices and ESP charges calculations confirm that C8 is the most favorable site of the electrophilic substitution. The calculated electronic properties (e.g, gap energy, electron affinity, and electronegativity) of aripiprazole and its iodinated form reveal the higher reactivity of iodinated aripiprazole compared with aripiprazole.

Conclusion: This may explain the higher affinity of iodinated aripiprazole and the increase of its radiochemical yield.

背景：阿立哌唑是一种喹啉酮衍生物。它对神经递质多巴胺和5-羟色胺受体显示出高度亲和力，可以克服血脑屏障（BBB）到达中枢神经系统（CNS）发挥治疗作用。其放射性碘化可导致高放射化学产率并改善其亲和力。阿立哌唑放射性碘化是一种芳香亲电取代基。

目的：在本文中，我们通过计算母体分子的重原子的Fukui指数和ESP电荷，研究了阿立哌唑的芳香亲电取代的有利原子位点。

方法：计算是在B3LYP / LanL2DZ理论水平上进行的。通过比较母体分子及其碘化形式的实验和预测的1H NMR化学位移，可以确认碘化阿立哌唑的结构。

结果：最后，在相同的理论水平上计算出阿立哌唑及其碘化形式的电子性质。亲核性福井指数和ESP电荷计算结果证实C8是亲电取代反应的最有利位点。计算得出的阿立哌唑及其碘化形式的电子性质（例如，能隙，电子亲和力和电负性）显示出碘化阿立哌唑的反应性高于阿立哌唑。

结论：这可能解释了碘化阿立哌唑具有更高的亲和力和放射化学产率的提高。