Synthesis, spectroscopic, topological, hirshfeld surface analysis, and anti-covid-19 molecular docking investigation of isopropyl 1-benzoyl-4-(benzoyloxy)-2,6-diphenyl-1,2,5,6-tetrahydropyridine-3-carboxylate

Arulraj Ramalingam; Murugavel Kuppusamy; Sivakumar Sambandam; Mouna Medimagh; Oluwatoba Emmanuel Oyeneyin; Amirthaganesan Shanmugasundaram; Noureddine Issaoui; Nathanael Damilare Ojo

doi:10.1016/j.heliyon.2022.e10831

Synthesis, spectroscopic, topological, hirshfeld surface analysis, and anti-covid-19 molecular docking investigation of isopropyl 1-benzoyl-4-(benzoyloxy)-2,6-diphenyl-1,2,5,6-tetrahydropyridine-3-carboxylate

Heliyon. 2022 Oct;8(10):e10831. doi: 10.1016/j.heliyon.2022.e10831. Epub 2022 Oct 2.

Authors

Arulraj Ramalingam¹, Murugavel Kuppusamy², Sivakumar Sambandam³, Mouna Medimagh⁴, Oluwatoba Emmanuel Oyeneyin⁵, Amirthaganesan Shanmugasundaram⁶, Noureddine Issaoui⁴, Nathanael Damilare Ojo⁷

Affiliations

¹ Department of Electrical and Computer Engineering, National University of Singapore, 117583, Singapore.
² PG & Research Department of Chemistry, Government Arts College, Chidambaram, Tamil Nadu, India.
³ Research and Development Centre, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India.
⁴ University of Monastir, Faculty of Sciences, Laboratory of Quantum and Statistical Physics (LR18ES18), Monastir, 5079, Tunisia.
⁵ Theoretical and Computational Chemistry Unit, Department of Chemical Sciences Adekunle Ajasin University, Akungba Akoko, Ondo State, Nigeria.
⁶ Department of Chemistry, Saveetha School of Engineering, Saveetha University, Chennai, Tamil Nadu, India.
⁷ Department of Chemistry, University of Ibadan, Oyo State, Nigeria.

Abstract

Isopropyl 1-benzoyl-4-(benzoyloxy)-2,6-diphenyl-1,2,5,6-tetrahydropyridine-3-carboxylate (IDPC) was synthesized and characterized via spectroscopic (FT-IR and NMR) techniques. Hirshfeld surface and topological analyses were conducted to study structural and molecular properties. The energy gap (E_g), frontier orbital energies (E_HOMO, E_LUMO) and reactivity parameters (like chemical hardness and global hardness) were calculated using density functional theory with B3LYP/6-311++G (d,p) level of theory. Molecular docking of IDPC at the active sites of SARS-COVID receptors was investigated. IDPC molecule crystallized in the centrosymmetric triclinic ( $P \bar{1}$ ) space group. The topological and Hirshfeld surface analysis revealed that covalent, non-covalent and intermolecular H-bonding interactions, and electron delocalization exist in the molecular framework. Higher binding score (-6.966 kcal/mol) of IDPC at the active site of SARS-COVID main protease compared to other proteases suggests that IDPC has the potential of blocking polyprotein maturation. H-bonding and π-cationic and interactions of the phenyl ring and carbonyl oxygen of the ligand indicate the effective inhibiting potential of the compound against the virus.

Keywords: Density functional theory; Hirshfeld surface analysis; Severe acute respiratory syndrome-coronavirus disease; Tetrahydropyridine-3-carboxylate; Topological analysis.