Topological analysis and reactivity study of monomeric and dimeric forms of 2‑methyl‑4(1H)‑quinolone: a computational study

Abstract

Context: Quinolone derivatives have gathered major attention largely due to their wonderful biological activities. Quinolones are a class of molecules that are derived from quinolines and also extracted from natural sources. Most of these quinolones have significant medicinal properties ranging from antiallergenic and anticancer to antimicrobial activities. Some bacteria produce several 2-alkyl-4(1H)-quinolones. In past years, a variety of methods have been reported for the synthesis of quinolone derivatives. In this present work, structural, wave functional, and electronic properties of monomeric and dimeric forms of 2-methyl-4(1H)-quinolone are investigated. From the calculated binding energies, it was found that the formation of dimers is thermodynamically favorable. The analysis of reactivity parameters confirms that the keto form is more reactive than the enol form and keto–keto dimer is more reactive than compared to all monomeric and dimeric forms of our studied compound. Methods: Geometry optimizations of monomers and dimers of studied molecules were carried out using the B3LYP-D3(BJ)/ ma-def2-TZVPP level of theory. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies were calculated using the B3LYP/def2-TZVP level of theory. All DFT calculations were done with the ORCA 5.0.3 program. The reactivity parameters such as ionization potential, electron affinity, global hardness, global softness, electronegativity, chemical potential, and electrophilicity index were calculated. The nature of intermolecular interactions within the dimers was studied using topological analysis such as atoms in molecule (AIM) and reduced density gradient (RDG) surface analyses. To visualize the electron delocalization in the dimer electron localization function (ELF) and localized orbital locator (LOL) studies were also performed. The analyses such as AIM, RDG, ELF, and LOL were carried out by the multifunctional wavefunction analysis program Multiwfn 3.8.