Marinescu Maria, Cinteză Ludmila Otilia, Marton George Iuliu, Chifiriuc Mariana-Carmen, Popa Marcela, Stănculescu Ioana, Zălaru Christina-Marie, Stavarache Cristina-Elena
Department of Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, Bucharest, 050663 Romania.
Department of Physical Chemistry, Faculty of Chemistry, University of Bucharest, Bucharest, 030018 Romania.
BMC Chem. 2020 Jul 25;14(1):45. doi: 10.1186/s13065-020-00697-z. eCollection 2020 Dec.
The tri-component synthesis of novel chiral benzimidazole Mannich bases, by reaction between benzimidazole, aqueous 30% formaldehyde and an amine, the biological evaluation and DFT studies of the new compounds are reported here. The H-NMR, C-NMR, FTIR spectra and elemental analysis confirm the structures of the new compounds. All synthesized compounds were screened by qualitative and quantitative methods for their in vitro antibacterial activity against 4 bacterial strains. DFT studies were accomplished using GAMESS 2012 software and HOMO-LUMO analysis allowed the calculation of electronic and structural parameters of the chiral Mannich bases. The geometry of 1-methylpiperazine, the cumulated Mullikan atomic charges of the two heteroatoms and of the methyl, and the value of the global electrophilicity index (ω = 0.0527) of the molecule is correlated with its good antimicrobial activity. It was found that the presence of saturated heterocycles from the amine molecule, 1-methyl piperazine and morpholine, respectively, contributes to an increased biological activity, compared to aromatic amino analogs, diphenylamino-, 4-nitroamino- and 4-aminobenzoic acid. The planarity of the molecules, specific bond lengths and localization of HOMO-LUMO orbitals is responsible for the best biological activities of the compounds.
本文报道了通过苯并咪唑、30%的甲醛水溶液与胺之间的反应，新型手性苯并咪唑曼尼希碱的三组分合成，以及新化合物的生物学评价和密度泛函理论（DFT）研究。氢核磁共振（H-NMR）、碳核磁共振（C-NMR）、傅里叶变换红外光谱（FTIR）和元素分析确定了新化合物的结构。所有合成的化合物都通过定性和定量方法对其针对4种细菌菌株的体外抗菌活性进行了筛选。DFT研究使用GAMESS 2012软件完成，最高已占分子轨道（HOMO）-最低未占分子轨道（LUMO）分析允许计算手性曼尼希碱的电子和结构参数。1-甲基哌嗪的几何结构、两个杂原子和甲基的累积穆利肯原子电荷以及该分子的全局亲电指数值（ω = 0.0527）与其良好的抗菌活性相关。研究发现，与芳香族氨基类似物二苯胺、4-硝基氨基和4-氨基苯甲酸相比，胺分子中分别存在饱和杂环1-甲基哌嗪和吗啉有助于提高生物活性。分子的平面性、特定键长以及HOMO-LUMO轨道的定位是这些化合物具有最佳生物活性的原因。
