Towards mismatched DNA photoprobes and photoreagents: “elbow-shaped” Ru(ii) complexes

Abstract

Due to their potentially harmful consequences, the detection of mismatched DNA is a subject of high interest. In order to probe DNA mismatches by means of luminescent sensitive Ru(II) complexes, “elbow-shaped” extended planar ligands based on an acridine or phenazine core have been synthesized (npp = naphtho[1,2-b]pyrido[3,2-f][1,7]phenanthroline and bdppz = benzo[h]dipyrido[3,2-a:2′,3′-c]phenazine). The photophysical studies revealed that [Ru(bpy)₂npp]²⁺ (bpy = 2,2′-bipyridine) allows emission from a ³MLCT_bpy/npp excited state, while the lowest ³MLCT for [Ru(bpy)₂bdppz]²⁺ shifts from a bright ³MLCT_bpy/pz state towards a poorly luminescent ³MLCT_bdp state, probably due to the formation of H-bonds with water molecules in the excited state. Studies of the complexes in the presence of DNA demonstrate that they strongly bind to polynucleotides. In the presence of single base mismatched hairpin oligonucleotides, while [Ru(bpy)₂npp]²⁺ does not show remarkable sensitivity to the nature of the mismatch site, [Ru(bpy)₂bdppz]²⁺ exhibits noticeably differential luminescence behavior correlated to the nature and stability of the mismatch compared to the well-matched sequence. Photooxidant analogues of these complexes were prepared, replacing bpy ancillary ligands by bpz (2,2′-bipyrazine). A photo-induced electron transfer from dGMP and polynucleotides to the excited states of [Ru(bpz)₂npp]²⁺ and [Ru(bpz)₂bdppz]²⁺ is observed. These results emphasized the role of “elbow-shaped” Ru(II) complexes as promising candidates for the development of mismatch-sensitive DNA photoprobes.