Golj Desta Regassa, Dinka Megersa Olumana, Sherefedin Umer, Belay Abebe, Gelanu Dereje, Megersa Gadisa Deme
Department of Civil Engineering Science, Faculty of Engineering and the Built Environment, University of Johannesburg Johannesburg 2006 South Africa.
Department of Applied Physics, School of Applied Natural Sciences, Adama Science and Technology University Adama, P.O. Box 1888 Ethiopia.
RSC Adv. 2025 Aug 11;15(35):28538-28554. doi: 10.1039/d5ra02359a.
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 semiempirical, Hartree-Fock (HF), and density functional theory (DFT) methods. Its binding with antibacterial drugs was also investigated 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.
甲硝唑作为一种抗菌药物被广泛使用，对厌氧菌和原生动物感染特别有效。本研究采用半经验方法、哈特里-福克（HF）方法和密度泛函理论（DFT）方法，研究了溶剂极性对甲硝唑傅里叶变换红外（FTIR）光谱、热力学和电子性质的影响。还通过分子对接研究了其与抗菌药物的结合情况。结果表明，在水中，偶极矩和极化率增加，表明溶解度和反应性增强。溶剂引起的键长和键角变化对于理解甲硝唑在生物系统中的行为很重要。FTIR揭示了由于溶剂化效应导致的分子相互作用变化，尤其是水中的氢键。热力学计算进一步表明，极性溶剂会增加能量和偶极矩，增强分子的反应性。前线分子轨道（FMO）分析表明，分子在极性环境中更稳定，而紫外-可见光谱位移表明溶剂会影响电子性质。与抗菌蛋白的分子对接研究表明，甲硝唑与蛋白强烈结合，甲硝唑-4kov复合物显示出最高的结合亲和力。甲硝唑与塞克硝唑、替唑尼特和咖啡因的分子对接增强了结合亲和力，表明存在协同效应。总之，本研究强调了溶剂极性对于优化甲硝唑抗菌性能及其与其他药物分子对接的重要性。
