*Article* **Increasing the Efficacy of Seproxetine as an Antidepressant Using Charge–Transfer Complexes**

**Walaa F. Alsanie 1,2, Abdulhakeem S. Alamri 1,2 , Hussain Alyami <sup>3</sup> , Majid Alhomrani 1,2 , Sonam Shakya <sup>4</sup> , Hamza Habeeballah <sup>5</sup> , Heba A. Alkhatabi 6,7,8, Raed I. Felimban 6,9 , Ahmed S. Alzahrani <sup>2</sup> , Abdulhameed Abdullah Alhabeeb <sup>10</sup>, Bassem M. Raafat <sup>11</sup>, Moamen S. Refat 12,\* and Ahmed Gaber 2,13,\***


**Abstract:** The charge transfer interactions between the seproxetine (SRX) donor and *π*-electron acceptors [picric acid (PA), dinitrobenzene (DNB), p-nitrobenzoic acid (p-NBA), 2,6-dichloroquinone-4-chloroimide (DCQ), 2,6-dibromoquinone-4-chloroimide (DBQ), and 7,70 ,8,80 -tetracyanoquinodi methane (TCNQ)] were studied in a liquid medium, and the solid form was isolated and characterized. The spectrophotometric analysis confirmed that the charge–transfer interactions between the electrons of the donor and acceptors were 1:1 (SRX: *π*-acceptor). To study the comparative interactions between SRX and the other *π*-electron acceptors, molecular docking calculations were performed between SRX and the charge transfer (CT) complexes against three receptors (serotonin, dopamine, and TrkB kinase receptor). According to molecular docking, the CT complex [(SRX)(TCNQ)] binds with all three receptors more efficiently than SRX alone, and [(SRX)(TCNQ)]-dopamine (CTcD) has the highest binding energy value. The results of AutoDock Vina revealed that the molecular dynamics simulation of the 100 ns run revealed that both the SRX-dopamine and CTcD complexes had a stable conformation; however, the CTcD complex was more stable. The optimized structure of the CT complexes was obtained using density functional theory (B-3LYP/6-311G++) and was compared.

**Keywords:** seproxetine; antidepressant; charge transfer; *π*-acceptors; DFT

**Citation:** Alsanie, W.F.; Alamri, A.S.; Alyami, H.; Alhomrani, M.; Shakya, S.; Habeeballah, H.; Alkhatabi, H.A.; Felimban, R.I.; Alzahrani, A.S.; Alhabeeb, A.A.; et al. Increasing the Efficacy of Seproxetine as an Antidepressant Using Charge–Transfer Complexes. *Molecules* **2022**, *27*, 3290. https:// doi.org/10.3390/molecules27103290

Academic Editors: Tanveer A. Wani, Seema Zargar and Afzal Hussain

Received: 27 April 2022 Accepted: 19 May 2022 Published: 20 May 2022

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