Quantum chemical analysis and anticancer evaluation of 1, 4-benzenedicarboxylic acid bis (2-ethylhexyl) ester: Topological indices,reduced density gradient, molecular electrostatic potential, natural bond orbital

Liver cancer remains one of the most lethal malignancies worldwide, highlighting the urgent need for improved
treatment strategies. This study employed density functional theory (DFT) quantum calculations and molecular docking
studies to evaluate the specificity and anticancer potential of therapeutic compounds derived from Hybanthus enneaspermus. The investigation focused on the interaction of 1, 4-Benzenedicarboxylic Acid, Bis (2-Ethylhexyl) Ester (4B2EH) with specific active methylene reagents and hydrogen nucleophiles. Global reactivity descriptors were utilized to assess the compound's molecular stability and reactivity against liver cancer. Compounds extracted through the Soxhlet technique were further confirmed using spectroscopic methods, including FT-IR, ¹H NMR, ¹³C NMR, GC-MS, and UV-Vis analyses. The electronic properties of 4B2EH were examined using the DFT/B3LYP/6-311++G (d, p) functional, employing timedependent density functional theory (TD-DFT) for advanced insights. The study utilized Veda 04 software for PED values, alongside Gaussian 09W, Gauss View 6.0, and ChemCraft 1.8 for comprehensive molecular visualization and analysis. The investigation focused on key aspects such as the MEP surface, HOMO-LUMO analysis, and NBO interactions, specifically C4 – C5 (π) → C10 – O11 (π*) and π → π* transitions. Additionally, DOS, RDG, ELF, and LOL analyses were conducted to predict the compound's stability, anticancer potential, and reactive sites for electrophilic and nucleophilic attacks. Furthermore, molecular docking simulations were performed against two distinct protein receptors (PDB ID: 2H80 and 9ETE) to evaluate binding conformations and interaction profiles with key liver cancer targets. The simulations revealed binding energies of -5.08 kcal/mol and -5.83 kcal/mol, indicating favourable interactions and potential therapeutic applications. Additionally, topological indices such as the 58.24 RR index, 5.87 RA index, and 5.89 S index demonstrated strong correlations with key molecular properties. These indices, combined with factors like polarity surface area and docking scores, play a crucial role in identifying potential lead compounds for drug development. The analysis highlights essential chemical attributes, biological activity, and other relevant data obtained through degree-based QSPR analysis.