DNA studies of newly synthesized heteroleptic platinum(II) complexes [Pt(bpy)(iip)]2+ and [Pt(bpy)(miip)]2+

Two new mono-nuclear heteroleptic platinum(II) complexes, [Pt(bpy)(iip)](PF6)(2) (1) and [Pt(bpy)(miip)](PF6)(2)center dot 2H(2)O (2) (bpy is 2,2'-bipyridine; iip is 2-(imidazo-4-yl)-1H-imidazo[4,5-f] [1,10] phenanthroline; miip is 2-(1-methylimidazo-2-yl)-1H-imidazo[4,5-f] [1, 10] phenanthroline), have been synthesized and fully characterized by CHN analysis, electrospray ionization and MALDI-TOF mass spectrometry, H-1 NMR, FT-IR (ATR), and UV-Vis spectrophotometer. Cytotoxicity, ability to inhibit DNA transcription and DNAse activity of the complexes were studied. The DNA-binding behaviors of both complexes have also been studied by spectroscopic methods, cyclic voltammetry and viscosity measurements. Both complexes showed cytotoxic properties and 2 was more cytotoxic than 1. DNA transcription was inhibited upon increasing concentrations of both complexes. The complex 2 was found to be a better inhibitor than 1. The same pattern can be seen in the DNAse profile of the complexes. In addition, 2 was found to promote cleavage of pBR322 DNA at a lower concentration than 1. The spectroscopic, electrochemical and viscometric results indicate that both complexes show some degree of binding to DNA in an intercalative mode, resulting in intrinsic binding constants K (b) = 3.55 +/- A 0.6 x 10(4) M-1 and 7.01 +/- A 0.9 x 10(4) M-1 for 1 and 2, respectively. The difference in the DNA-binding affinities of 1 and 2 may presumably be explained by the methylated imidazole nitrogen atom that makes the compound more hydrophobic and gives better intercalative binding ability to DNA's hydrophobic environment.