Synthesis, Crystal Structure, and Molecular Docking Analysis of 1-(3 Pyrrolidin-2 Insights Into Biological Interactions and Drug Design

Abstract

A novel compound, 1-(3-(2-chlorophenyl)-4,5-dihydroisoxazol-5-yl)pyrrolidin-2-one (CDPO), was synthesized via 1,3-dipolar cycloaddition with a yield of 40% and melting point of 178-180 degrees C. The structure was confirmed by NMR, FT-IR, HRMS (m/z = 265.0733), and single-crystal X-ray diffraction. Crystallographic analysis revealed a triclinic system with space group P-1, unit cell volume of 636.33 & Aring;3, and key hydrogen bonding and pi-pi stacking interactions (centroid distance = 3.956 & Aring;). Hirshfeld surface analysis showed H & sdot;& sdot;& sdot;H (40.5%) and O & sdot;& sdot;& sdot;H/ H & sdot;& sdot;& sdot;O (20.1%) contacts as dominant contributors to crystal stability. DFT calculations (B3LYP/6-311G(d,p)) confirmed structural agreement (e.g., C=O bond = 1.218 & Aring;) and revealed a HOMO-LUMO gap of 5.086 eV, with an ionization potential of 6.844 eV and electrophilicity index of 3.640 eV. ADMET predictions indicated good gastrointestinal absorption and blood-brain barrier permeability. Molecular docking (AutoDock 4.2) against six protein targets showed the strongest affinities with CYP3A4 (-6.32 kcal/ mol, Ki = 23.4 mu M) and CYP1A2 (-6.12 kcal/mol, Ki = 32.8 mu M). Moderate binding was observed with Muscarinic M2 (-5.36 kcal/mol) and Serotonin 5-HT2B (-5.14 kcal/mol), while weak interaction was noted with Histamine H1 (-3.04 kcal/mol). The docking protocol was validated with a redocking RMSD of 1.835 & Aring;. The data suggest CDPO as a promising scaffold with potential anticancer and neuroactive properties through multi-target modulation. Further in vitro and pharmacokinetic evaluations are warranted to explore therapeutic applications and off-target risks.