Synthesis, Spectroscopic Characterization, DFT Analysis, and Molecular Docking Studies of a Nitrosopiperidin-4-one Derivative toward Antiviral Applications

The nitrosopiperidinone derivative 2,6-bis(4-chlorophenyl)-3-isopropyl-1-nitrosopiperidin-4-one (BCINP) was synthesized and structurally characterized using FT-IR, one- and two-dimensional NMR ( 1 H, 13 C, and COSY) spectroscopic techniques. Density functional theory (DFT) calculations performed at the B3LYP/6-311++G(d,p) level provided optimized molecular geometries, revealing the coexistence of syn and anti-chair conformations influenced by nitrogen lone-pair effects and conformational strain. Intermolecular interactions in the crystalline state were investigated through Hirshfeld surface analysis, which indicated that H⋯O/O⋯H and H⋯C/H⋯C contacts are the predominant contributors to crystal packing, highlighting the role of weak hydrogen-bonding and π-associated interactions. Electronic structure analysis showed a HOMO–LUMO energy gap of 4.97 eV, suggesting moderate chemical reactivity and intramolecular charge transfer characteristics. Molecular electrostatic potential mapping and Topological analyses (AIM, NCI-RDG, ELF, LOL) revealed electron density (ρ = 0.02135 a.u.), Laplacian ∇ 2 ρ = 0.16054 a.u., and RDG isosurface range of –0.035 to 0.02 a.u., confirming weak non-covalent interactions, were employed to elucidate charge distribution and bonding features relevant to molecular recognition. Molecular docking studies demonstrated favorable binding interactions of BCINP with viral neuraminidase and cancer metastasis–associated protein targets (PDB IDs: 2PG5, 2FDV, 2FDY, 2FDU, 3LOP, and 5GWN), with predicted binding energies ranging from –7.9 to –5.9 kcal/mol. In silico ADMET and toxicity predictions suggested acceptable pharmacokinetic behavior and a favorable safety profile. Overall, the combined experimental and computational results indicate that BCINP represents a nitrosopiperidinone scaffold with potential antiviral (in silico) candidate for further evaluation.

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Publication Details

Journal
Journal of Computational Biophysics and Chemistry
Published
2026-06-12
DOI
https://doi.org/10.1142/s273741652650095x
Primary Topic
Nonlinear Optical Materials Research
Type
article
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Synthesis, Spectroscopic Characterization, DFT Analysis, and Molecular Docking Studies of a Nitrosopiperidin-4-one Derivative toward Antiviral Applications

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Synthesis, Spectroscopic Characterization, DFT Analysis, and Molecular Docking Studies of a Nitrosopiperidin-4-one Derivative toward Antiviral Applications

Arulraj Ramalingam, Ahlam Roufieda Guerroudj, Merzouk Saidj, Abdelkader Chouaıh, Sivakumar Sambandam, Balamurugan Arumugam, Abdullah Yahya Abdullah Alzahrani, Adhilakshmi Arumugam, Maruthavanan Thiyagarajan, Mahendhiran Ramasamy
article en

Abstract

The nitrosopiperidinone derivative 2,6-bis(4-chlorophenyl)-3-isopropyl-1-nitrosopiperidin-4-one (BCINP) was synthesized and structurally characterized using FT-IR, one- and two-dimensional NMR ( 1 H, 13 C, and COSY) spectroscopic techniques. Density functional theory (DFT) calculations performed at the B3LYP/6-311++G(d,p) level provided optimized molecular geometries, revealing the coexistence of syn and anti-chair conformations influenced by nitrogen lone-pair effects and conformational strain. Intermolecular interactions in the crystalline state were investigated through Hirshfeld surface analysis, which indicated that H⋯O/O⋯H and H⋯C/H⋯C contacts are the predominant contributors to crystal packing, highlighting the role of weak hydrogen-bonding and π-associated interactions. Electronic structure analysis showed a HOMO–LUMO energy gap of 4.97 eV, suggesting moderate chemical reactivity and intramolecular charge transfer characteristics. Molecular electrostatic potential mapping and Topological analyses (AIM, NCI-RDG, ELF, LOL) revealed electron density (ρ = 0.02135 a.u.), Laplacian ∇ 2 ρ = 0.16054 a.u., and RDG isosurface range of –0.035 to 0.02 a.u., confirming weak non-covalent interactions, were employed to elucidate charge distribution and bonding features relevant to molecular recognition. Molecular docking studies demonstrated favorable binding interactions of BCINP with viral neuraminidase and cancer metastasis–associated protein targets (PDB IDs: 2PG5, 2FDV, 2FDY, 2FDU, 3LOP, and 5GWN), with predicted binding energies ranging from –7.9 to –5.9 kcal/mol. In silico ADMET and toxicity predictions suggested acceptable pharmacokinetic behavior and a favorable safety profile. Overall, the combined experimental and computational results indicate that BCINP represents a nitrosopiperidinone scaffold with potential antiviral (in silico) candidate for further evaluation.

Journal of Computational Biophysics and Chemistry
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Nonlinear Optical Materials Research
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