Substitution effect on new Schiff base ligand in complexation with some divalent metal ion; synthesis, characterization, DFT and cytotoxicity studies

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New transition metal complexes were prepared from Schiff base ligands derived from bromo/nitro salicylaldehyde derivatives and pyrazine have the general formula M[4-bromo-2-((pyrazin-2-ylamino)methyl)phenol]n. and M[4-nitro-2-((pyrazin-2-ylamino)methyl)phenol]n. the molar ratio along with spectral measurements and thermal analysis. Density functional theory calculations at the B3LYP level of theory were used to optimize the geometries of the synthesized complexes and compute the essential parameters. Based on charge distribution analysis, the bromide-substituted ligand was better able to bind metals with a 2:1 ligand-to-metal ratio than the nitro-substituted ligand. The biological properties of the complexes were predicted using quantum chemical calculations and their biological activity was explored using DNA binding, molecular docking, and cytotoxicity tests. The binding constants were spectroscopically determined to be in the range of 7.14 × 105–5 × 105 M−1. The complexes exhibited two types of interactions with calf thymus DNA (CT-DNA): intercalative and groove interactions. To obtain further insights into the binding behavior, molecular docking studies were carried out with three receptor proteins associated with melanoma, ovarian cancer, and non-small-cell lung cancer. Moreover, the anticancer activities of the new complexes were studied by in vitro assay with three cancer cell lines. The obtained cytotoxicity results revealed an equal biological activity of two ligands with better inhibition of L1. Among all the metal complexes, the Cu(II)–L1 complex showed the strongest inhibitory activity against three cancer cell lines.