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 2.25×10 4   M −1 and 3.07×10 6   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.