Synthesis, characterization and anticancer properties: A series of highly selective palladium(II) substituted-terpyridine complexes

Ten new palladium(II) complexes [PdCl(L1−10)]Cl have been synthesized by the reaction of palladium(II) chloride and ten 4′-(substituted-phenyl)-2,2′:6′,2′′-terpyridine ligands bearing hydrogen(L1), p-hydroxyl(L2), m-hydroxyl (L3), o-hydroxyl (L4), methyl (L5), phenyl (L6), fluoro (L7), chloro (L8), bromo (L9), or iodo (L10). Their structures were confirmed by FT-IR, 1H NMR, elemental analysis and/or single crystal X-ray diffraction analysis. Their in vitro anticancer activities were investigated based on five cell lines, including four cancer cell lines (A549, Eca-109, Bel-7402, MCF-7) and one normal cell line (HL-7702). The results show that these complexes possess a strong killing effect on the cancer cells but a weak proliferative inhibition on the normal cells, implying their high inhibitory selectivity for the proliferation of the cancer cell lines. Flow cytometry characterization reveals that these complexes affect cell proliferation mainly in the G0/G1 phase and induce the late apoptotic of the cells. The quantity of palladium(II) ion in extracted DNA was determined by ICP-MS, which proved that these complexes target genomic DNA. And the strong affinity of the complexes with CT-DNA were confirmed by UV–Vis spectrum and circular dichroism (CD). The possible binding modes of the complexes with DNA were further explored by molecular docking. As the concentration of complexes 1–10 gradually increases, the fluorescence intensity of bovine serum albumin (BSA) decreases by a static quenching mechanism.