Structural, Spectroscopic, and Theoretical Investigation of a 4‐Benzyl Piperidine Derivative with Multi‐Targeted Bioactivity

ABSTRACT A new crystalline tertiary aryl amine, 1‐(4‐Nitrophenyl)‐4‐benzylpiperidine (NPBP), was synthesized via a nucleophilic substitution reaction between 4‐benzylpiperidine and 1‐chloro‐4‐nitrobenzene. The structure was confirmed using infrared (IR) spectroscopy, 1 H, and 13 C nuclear magnetic resonance (NMR) spectroscopy. Single‐crystal x‐ray diffraction analysis revealed that NPBP crystallizes in the orthorhombic, chiral, non‐centrosymmetric space group P2 1 2 1 2 1 with unit cell parameters a = 6.0972(10) Å, b = 8.3575(11) Å, c = 30.373(5) Å, and α = β = γ = 90°. Hirshfeld surface and energy framework analyses highlighted significant intermolecular interactions contributing to crystal stability. Density functional theory (DFT) calculations indicated both electron‐donating and electron‐accepting character, supporting its potential reactivity. Molecular docking studies showed strong binding affinities with EGFR tyrosine kinase, human cyclooxygenase, as well as with DNA and bovine serum albumin (BSA). Binding interactions with calf thymus DNA (CT‐DNA) and BSA were further validated by UV–visible spectroscopic titrations. In vitro assays demonstrated moderate anticancer and anti‐inflammatory activities, suggesting NPBP as a promising lead compound for future therapeutic development.