Quantum chemical evaluation, ELF, LOL analysis, Fukui, herbicide-likeness and molecular docking studies of 4-methyl-phenoxyacetic acid, 4-acetyl-phenoxyacetic acid and 4-tert-butyl-phenoxyacetic acid – a comparative study

The phenoxyacetic acid and its derivatives have attracted considerable attention as they have proven to be excellent bioactive herbicides. The optimized molecular geometry and the fundamental vibrational frequencies of 4-methyl-phenoxyacetic acid (4MPA), 4-acetyl-phenoxyacetic acid (4APA) and 4-tert-butyl-phenoxyacetic acid (4TBPA) have computed using density functional theory (DFT) method with 6–311++G(d,p) basis set. The theoretically predicted wavenumbers are found to be in close agreement with the experimentally determined one. The band gap energy of HOMO and LUMO depicts the charge transfer interactions occurring within the molecules. Global reactivity descriptors have utilized to assess the chemical reactivity. It has been observed that 4APA exhibits good electrophilic properties with a higher electrophilicity index (ω = 2.993 eV) compared to other compounds such as 4TBPA and 4MPA. The molecular electrostatic potential surface (MESP) has been plotted over the optimized structure to estimate the reactive sites of electrophilic and nucleophilic attacks on the phenoxyacetic acid molecule. Fukui function is also used to analyze their electrophilic and nucleophilic descriptors with Hirshfeld charges. Electron localization function (ELF) and local orbital localizer (LOL) are discussed using the multifunction wavefunction (Multiwfn) analyzer. Using the HerbiPAD tool, the herbicide-likeness parameter has exposed the good herbicide-like behaviour of the title compounds. Additionally, the Tice rule and pK_a are described, providing valuable insights into the herbicidal activity of phenoxyacetic acid compounds. The 4APA compound is highly effective, which exhibits more herbicidal activity when interacting with the auxin receptor TIR1. It demonstrates a strong binding affinity of -8.56 kcal/mol.