Rapid ultrasound-assisted synthesis, characterization, DFT, molecular docking, and anticancer activity of palladium and zinc complexes with 2,6-dimethoxybenzoic acid: A comprehensive study

Abstract

In this work, we present a thorough investigation encompassing various aspects of zinc and palladium complexes synthesized with 2, 6-dimethoxybenzoic acid. The complexes were prepared through an ultrasonic reaction, offering a rapid, cost-effective, and environmentally friendly method. Characterization of the complexes, prepared in a 1:2 metal-to-ligand ratio, was carried out using elemental analysis, infrared spectra, proton nuclear magnetic resonance, molar conductivity, and melting point measurements. The results revealed that the ligand exhibited chelating bidentate behavior, forming coordination bonds through both oxygen atoms of the carbonyl group. The prepared complexes were evaluated for their anticancer activity against breast cancer and colon cancer cell lines. Remarkably, the complexes exhibited significantly higher cancer cell-killing potential compared to the commonly used drug 5-fluorouracil, with cell death rates reaching 99% for both complexes. To gain insights into the underlying mechanisms of this enhanced anticancer activity, molecular docking studies were conducted, revealing a binding energy of no more than -9.14 kcal/mol between the complexes and the amino acids of the cancer cells. Furthermore, theoretical studies employing Density Functional Theory (DFT) were performed to provide additional diagnostic insights. These studies encompassed molecular structural analysis, computational vibrational properties, natural bond orbital analysis (NBO) and FMOs, electronic properties (UV–Vis spectra), average local ionization energy (ALIE), electrostatic potential (ESP), electron localization function (ELF), and reduced density gradient (RDG/NCI) analyses. The comprehensive investigation presented in this study sheds light on the synthesis, characterization, theoretical analysis, and remarkable anticancer potential of zinc and palladium complexes with 2,6-dimethoxybenzoic acid.