Pt(II) and Pd(II) complexes bearing 1,10-phenanthroline-based ligands: Distinct binding modes to DNA and anticancer activities.

The Pt(II) and Pd(II) complexes with 1,10-phenanthroline derivative ligands, [Pt(L)(py)2](PF6)2 and [Pd(L)(py)2](PF6)2 (L = dipyrido[3,2-a:2',3'-c]phenazine (dppz) or 10,11,12,13-tetrahydrodipyrido[3,2-a:2',3'-c]phenazine (thdppz)), were synthesized, and their interactions with calf thymus DNA (ct-DNA) and anticancer activities against A549 cells (adenocarcinoma of the lung) were investigated. The electronic states and chemical properties (e.g., the stability in aqueous solution) of these Pt and Pd complexes were very similar to each other; however, their interactions with biomolecules such as DNA and bovine serum albumin differed substantially. From the ESI-MS data of each complex with guanosine, guanosine adducts of both Pd complexes were observed, while no guanosine adducts of the Pt complexes were observed. The CD and ESI-MS results suggested that [Pt(dppz)(py)2](PF6)2 interacts via intercalation, whereas [Pt(thdppz)(py)2](PF6)2 binds through electrostatic interactions. It was revealed that [Pd(dppz)(py)2](PF6)2 and [Pd(thdppz)(py)2](PF6)2 interact via a coordinate covalent bonding. Both Pd complexes exhibited strong cytotoxicity, although the Pt complexes showed no cytotoxicity. These results indicate that the anticancer activity of the Pd complexes strongly depends on their substitution activity. In addition, among the investigated complexes, [Pt(dppz)(py)2](PF6)2 is expected to be the most effective anticancer drug against cisplatin-resistant cancers because it interacts with ct-DNA through a different binding mode to that for cisplatin.