Solvent polarity effects on the FTIR spectrum, and thermodynamic and electronic properties of metronidazole and its binding with antibacterial drugs: a DFT and molecular docking study.

Metronidazole is widely used as an antimicrobial, particularly effective against anaerobic bacteria and protozoan infections. This study investigates solvent polarity effects on the Fourier transform infrared (FTIR) spectrum, and thermodynamic and electronic properties of metronidazole via semiempirical, Hartree-Fock (HF), and density functional theory (DFT) methods. Its binding with antibacterial drugs was also investigated via molecular docking. The results showed that in water, the dipole moment and polarizability increased, indicating enhanced solubility and reactivity. Solvent-induced changes in bond lengths and angles are important for understanding the behavior of metronidazole in biological systems. FTIR reveals changes in molecular interactions due to solvation effects, especially hydrogen bonding in water. Thermodynamic calculations further revealed that polar solvents increase the energy and dipole moment, enhancing the reactivity of the molecule. Frontier molecular orbital (FMO) analysis indicated that the molecules are more stable in polar environments, while UV-Vis spectral shifts showed that the solvent affects the electronic properties. Molecular docking studies with antibacterial proteins revealed that metronidazole binds strongly to proteins, with the metronidazole-4kov complex showing the highest binding affinity. Molecular docking of metronidazole with secnidazole, tizoxanide, and caffeine enhances the binding affinities, suggesting synergistic effects. In conclusion, this study emphasizes the importance of solvent polarity for optimizing the antibacterial properties of metronidazole and its molecular docking with other drugs.