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 C1 symmetry while in solution, the 1H and 13C 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 t2g 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 intra-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 ∼ 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.