A [4+2] mixed ligand approach to ruthenium DNA metallointercalators [Ru(tpa)(N-N)](PF6)2 using a tris(2-pyridylmethyl)amine (tpa) capping ligand

A series of five tris(2-pyridylmethyl)amine (tpa) ruthenium complexes [Ru(tpa)(N-N)](PF6)(2) with N-N=bpy (2,2'-bipyridine), phen (1,10-phenanthroline), dpq (dipyrido[3,2-d:2',3'-f]quinoxaline), dppz (dipyrido[3,2-a;2'.3'-c]phenazine), and dppn (4,5,9,16-tetraazadibenzo[a,c]naphthacene) was prepared and characterized by NMR, UV-Visible (UV/Vis). and fluorescence spectroscopy as well as cyclic voltammetry. Structures optimized with density functional theory methods (DFT, BP86, TZVP) without constraints show C-i symmetry while in solution, the H-1 and C-13 NMR spectra are in accordance with an average CS symmetry. This is thought to be due to a low energy barrier for flipping of the equatorial pyridine ring from one side of the N-N plane to the other. The electronic structure of the compounds was studied with DFT and a change in the highest occupied molecular orbital (HOMO) character from Ru t(2g) for the bpy, phen, and dpq to N-N ligand-based for the dppz and dppn complexes was found. TDDFT calculations showed dominant N-N-based infra-ligand charge transfer (ILCT) transitions in the latter two complexes mixed with metal-to-ligand charge transfer (MLCT) bands found for all five compounds. DNA binding of the complexes was studied with UV/Vis titrations, the fluorescent ethidium bromide displacement assay, and CD spectroscopy. The affinity increases with the aromatic surface area of of the bidentate N-N ligand in the order bpy phen << dpq < dppz similar to dppn. Viscosity measurements support an intercalative binding mode for the latter three compounds, while the others did not show a pronounced effect of the hydrodynamic properties of calf thymus (CT) DNA. (C) 2009 Elsevier Inc. All rights reserved.