Synthesis and Biological Activity of a Platinum(II) 6-Phenyl-2,2′-bipyridine Complex and Its Dimeric Analogue

We have synthesized (pyridyl)-(6-phenyl-2,2′-bipyridine)platinum(II) hexafluorophosphate (1) and its corresponding dimer, μ-N,N′-bis(isonicotinyl)-1,6-hexanediamino bis-[6-phenyl-2,2′-bipyridine-platinum(II)] dichloride (2). The DNA binding constants of 1 and 2 at 20 °C were determined by absorption titration to be 2.25×10⁴ M⁻¹ and 3.07×10⁶ M⁻¹, respectively. Compound 1 showed an AT preference, while 2 had no base preference. The binding site sizes of 2 for [poly(dA-dT)]₂, calf thymus DNA (ctDNA), and [poly(dG-dC)]₂, as determined by fluorescence titration, were 6.6, 4.0, and 2.8 bp, respectively. Compound 2 probably bound to [poly(dA-dT)]₂ through bisintercalation, and to [poly(dG-dC)]₂ by monointercalation. Binding of DNA by both complexes is favorable, since the binding free energies of 1 and 2 were estimated to be −5.8 and −8.7 kcal mol⁻¹, respectively. The results of viscosity measurements and gel mobility shift assay demonstrated that binding of 1 and 2 caused DNA lengthening. The cytotoxicities of the complexes in various human cancer cell lines were determined by MTT assay. Complex 2 exhibited cytotoxicity comparable to that of cisplatin, and was more toxic than 1 by an order of magnitude.