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The reactions of copper chloride and 4′-(4′-substituted-phenyl)-2,2′:6′,2′′-terpyridine ligands bearing nitro ( L 1), methyl ( L 2), phenyl ( L 3), tolyl ( L 4) and carboxyl ( L 5) gave five copper compounds ( 1 – 5 ) which have mononuclear structures with their Cu(II) ions five-coordinate in the irregular square pyramidal geometries. Their  in vitro  biological properties were evaluated by CCK-8 assay, which show remarkable proliferation inhibitive properties on the cancer cell lines including A549, Eca-109, and Bel-7402, and two human normal cell lines (HL-7702 and HLF). The values of IC 50  indicate better anticancer activities of these compounds than that of cisplatin. Compound  2  with methyl group exhibits the best anticancer activity, with IC 50  value &lt; 2.5 µM on all the tested cancer cells. The interactions of the compounds with DNA were evaluated using UV–Vis absorption titrations, circular dichroism spectroscopy, and DNA viscosity. The complexes show significant insertion binding with DNA sequences and strong intercalator binding mode with DNA sequences. Compounds  1 – 5  interact with the functional groups of DNA through π···π stacking, van der Waals interactions, hydrophobic interactions, and hydrogen bonds as determined by molecular docking. In addition, strong binding interactions between the five copper(II) complexes and bovine serum albumin (BSA) were studied by fluorescence titration and circular dichroism spectroscopy.

Anticancer activities and DNA/BSA interactions for five Cu(II) compounds with substituted terpyridine ligands