Design, structural inspection of new bis(1H-benzo[d]imidazol-2-yl) methanone complexes: Biomedical applications and theoretical implementations via DFT and docking approaches

In the present study, a novel bis(1H-benzo[d]imidazol-2-yl)methanone (H2L) ligand derived from the interaction of 1,2-phenylenediamine with diethyl 2-bromomalonate and its metal chelates of Zinc (II), Nickel (II), Copper (II) and Iron (III) were synthesized. The IR, NMR, and mass spectra were used to confirm the formation of the ligand. The new metal chelates were studied by analysis of elements, magnetic susceptibility measurements, Molecular vibrational and absorption spectra, and thermal analysis to describe their nature. The elemental analysis suggests metal to a ligand by 1:1 stoichiometry for all metal chelates under inspection. The ligand coordinates as a neutral tri-dentate towards the central metal ions through ONN donors that form a chelating five-member ring. The physicochemical studies suggested an octahedral geometry for the metal chelates under inspection. Various kinetic parameters have been determined from the thermal data by using Coats-Redfern route. The geometries of all current compounds were optimized by using the advanced program to verify the binding mode of the ligand towards the metal ions and to estimate common reactivity features. Mulliken charges were computed and N(9), N (16) and O(11) donors appeared with high negativity compared to the other donors, which supports their priority in coordination. Furthermore, the new synthesizers were screened in vitro for their biomedical capacity versus inspected strains of bacteria and fungi. Moreover, all the metal chelates have better biomedical efficiency than the ligand. Moreover, the in vitro antiproliferative influence of the BIM ligand and its chelates were screened versus variable carcinoma cell lines. The antiproliferative efficacy of the metal chelates was outstanding with significant IC50 values versus the tested cancer cells compared to the ligand alone. Interestingly, these outcomes have been confirmed via two silico approaches as Swiss/ADME and docking (MOE). Swiss/ADME study supposed the best bioavailability of BIM ligand and its Cu(II) metal chelate (BIMCu). While the MOE docking was performed for the most effective agent among all compounds (BIMCu). The reactivity of such a complex was recorded with 2rkb, 2bem and 4ewp proteins. Consequently, the promising feature of the BIMCu complex was clearly expected for liver cancer cells and bacteria.

Automated summary

A novel bis(1H-benzo[d]imidazol-2-yl)methanone (H2L) ligand and its metal chelates of Zinc (II), Nickel (II), Copper (II), and Iron (III) were synthesized. The metal chelates demonstrated better biomedical efficiency than the ligand alone. The most effective agent, BIMCu, showed outstanding antiproliferative efficacy against cancer cells.