Synthesis, DFT studies, and multi-target in silico evaluation of a piperidine-based sulfonohydrazide derivative...

A novel piperidine-based sulfonohydrazide derivative (BPMBS) was successfully synthesized and structurally characterized using FT-IR, ^1H NMR, and ^13C NMR spectroscopy. The FT-IR spectrum displayed characteristic absorption bands corresponding to N-H, C=N, and S=O functional groups, confirming the formation of the hydrazone framework. Density Functional Theory (DFT) calculations performed at the B3LYP/6-311++G(d,p) level showed excellent agreement with experimental geometrical parameters (R = 0.9981), validating the optimized molecular structure. Vibrational frequency analysis supported by potential energy distribution (PED) enabled reliable assignment of key vibrational modes, including S=O stretching (1237-1230 cm⁻¹), N-H stretching (3309 cm⁻¹), and C=N stretching (1639 cm⁻¹). Natural Bond Orbital (NBO) analysis revealed significant intramolecular charge transfer through n→π* and n→σ* interactions, particularly involving the sulfonyl and hydrazone moieties. Frontier molecular orbital (FMO) analysis indicated a narrow HOMO-LUMO energy gap of 3.39 eV, suggesting enhanced chemical reactivity and polarizability. Molecular electrostatic potential (MEP) mapping identified oxygen and nitrogen atoms as preferred sites for electrophilic and hydrogen-bonding interactions. BPMBS also exhibited notable nonlinear optical (NLO) properties, with a high first-order hyperpolarizability (β。 = 1.368 × 10⁻³⁰ esu). TD-DFT calculations predicted π→π* dominated electronic transitions in the 252-262 nm range, consistent with experimental UV-Visible spectra. Molecular docking, molecular dynamics simulations (200 ns), and in silico ADMET analysis demonstrated strong binding affinity, dynamic stability, favorable drug-likeness, and acceptable pharmacokinetic properties of BPMBS against key SARS-CoV-2 proteases. Overall, the results suggest BPMBS as a promising lead compound for further experimental antiviral evaluation.