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Current Organic Synthesis

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ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

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Research Article

Electrophilic Aromatic Synthesis of Radioiodinated Aripiprazole: Experimental and DFT Investigations

Author(s): Moustapha E. Moustapha, Mohammed H. Geesi, Zeinab R. Farag and El Hassane Anouar*

Volume 17, Issue 4, 2020

Page: [295 - 303] Pages: 9

DOI: 10.2174/1570179417666200409145824

Price: $65

Abstract

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.

Keywords: Aripiprazole, oxidative iodination, electrophilic substitution, fukui indices, GIAO, DFT.

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