Structural, topological, vibrational, and electronic analysis, and ADMET study of methyl-2-(4-isobutylphenyl)propanoate

Abstract

In this work, the methyl ibuprofen ester, named methyl-2-(4-isobutylphenyl)propanoate (C14H20O2, hereinafter MET-IBU).was synthesized and characterized by 1D- and 2D-NMR, ATR-FTIR, FT-Raman, and UV–Vis spectroscopy, while their structural, QTAIM topological and spectroscopic properties were investigated using DFT calculations. Through the analysis of the topological properties of the electron density computed at bonding critical points (BCP's) for MET-IBU molecule were determined the electron density, the Laplacian of electron density, the eigenvalues of Hessian matrix, the ellipticity of electron density, the potential energy density, the kinetic energy density in the Lagrangian and Hamiltonian forms, the total energy density, the Lagrangian density, and the electron delocalization index. Density Functional Theory (DFT) calculations were also used to determine the vibrational normal modes, the frontier molecular orbitals (FMOs), the dipole moment, and the molecular electrostatic potential (MEP) of MET-IBU. Theoretical UV absorption spectrum was also evaluated from time-dependent density functional theory (TD-DFT) providing the electronic transitions, which are expected for this compound. The molecular descriptors of the properties of absorption, distribution, metabolism and excretion, and toxicity (ADMET) were obtained. Empirical models for estimating ADME attributes showed that the MET-IBU has a distribution volume that allows permeability and activity in the Central Nervous System - CNS, with structural contributions from the side chain of isobutyl and methoxy that favor liver metabolism and excretion with a low toxic response. Furthermore, the MET-IBU does not have ionizable centers compared to its analog Ibuprofen constituting a more lipophilic chemical product.