Investigation of crystal structures, spectral (FT-IR and NMR) analysis, DFT, and molecular docking studies of novel piperazine derivatives as antineurotic drugs

• Published in: Journal of molecular structure 2023-04, Vol.1278, p.134937, Article 134937
• Main Authors: Jaziri, Emna, Louis, Hitler, Gharbi, Chaima, Lefebvre, Frédéric, Kaminsky, Werner, Agwamba, Ernest C., Egemonye, ThankGod C., Unimuke, Tomsmith O., Ikenyirimba, Onyinye, J., Mathias, Gideon E., Nasr, Chérif Ben, Khedhiri, Lamia
• Format: Article
• Language: English
• Subjects: Antineurotic agents; DFT; Molecular docking; Piperazine; Psychopharmacological; X-ray diffraction study
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.134937

•Hybrid piperazine derivatives named PIP1 and PIP2 were synthesized.•XRD, FT-IR and NMR characterized (PIP1) and (PIP2).•DFT studies were performed on (PIP1) and (PIP2) at B3LYP/6-311++G(d,p).•FMO disclosed that (PIP1) is more stable than (PIP2) due to its high energy gap.•Molecular docking revealed that (PIP1) and (PIP2) bind with the neurotic enzymes. In this article, the psychopharmacological potential of piperazine derivatives as an antineurotic agent was presented. Crystal and molecular structure of newly synthesized hybrid piperazine derivatives; (C12H20N2)(ClO4).2H2O≡ (PIP1) and (C11H18N20)(ClO4)2.nH2O ≡ (PIP2) were characterized using FT-IR, X-ray crystallographic data and solid-state NMR spectroscopy. First principles computations were performed on the synthesized structures to comprehend their molecular electronic properties at the DFT/B3LYP/6–311++G(d,p) level of theory. Investigations of the Hirshfeld surfaces of (PIP1) and (PIP2) disclose that N-H···O and O-H···O hydrogen bonds between the organic and inorganic parts, constitute the principal contributors to the intermolecular stabilization within the crystal packing. The results from the computational investigation showed that the conformation of (PIP1) and (PIP2) are in correlation with the experimental results. Furthermore, molecular properties disclosed that (PIP1) is more stable compared to (PIP2) due to its high energy gap value. Also, the Fukui function, Mulliken charges, and electrostatic potential iso-surface maps, explicitly disclosed the various susceptible regions that could bind with the GIRK channel. Molecular docking result displayed that (PIP1) and (PIP2) significantly binds with the active sites of the neurotic enzymes and thus, can be considered potential psychopharmacological and antineurotic agents. [Display omitted]