Synthesis, characterization, thermodynamic, topology, pharmacokinetics analysis, and investigation of fibrinolytic activity of methyl-2-(4-methylbenzyloxy)benzoate by molecular docking and dynamic simulation

A novel compound, methyl 2-(4-methylbenzyloxy)benzoate (MB), has been successfully synthesized by condensation of methyl salicylate with 4-methylbenzyl bromide in the presence of anhydrous K₂CO_3. The compound has been structurally characterized using FTIR,¹H NMR and mass spectroscopy. To gain detailed information on the structural features and predict the vibrational frequencies, the Density Functional Theory (DFT) method was employed at the B3LYP level of theory with the 6–311++G(d,p) basis set. The theoretical results showed a strong correlation with the experimental data of the compound. The IEFPCM model, applied to study the solvent effect, revealed increased NLO properties and electrostatic potential with increasing solvent polarity. In contrast, the polarity of solvent reduced the energy gap between HOMO and LUMO. The hyperpolarizability is approximately 12 times higher than that of urea in water solvent, while 7.48 times higher in the gas phase. Both the experimental and computational UV–Vis spectra exhibited π→π* and n→π* transitions, which were further supported by application of Natural Bond Orbital (NBO) analysis. Topology analysis described the electron charge density distribution and the intramolecular electrostatic interaction of MB. Fukui function analysis predicted multiple sites for electrophilic, nucleophilic, and radical attacks. The ADMET parameters and pass prediction exhibited good fibrinolytic activity, as evidenced by a binding affinity of −7.8 kcal/mol with the Plasminogen Activator Inhibitor-1 (PAI-1) gene, known as an antifibrinolytic agent. Moreover, the results of several dynamic simulation studies suggested the formation of a stable protein-ligand complex.