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, micro-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 degrees C were determined by absorption titration to be 2.25 x 10(4) M(-1) and 3.07 x 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.