Luminescence of [Ru(bpy)₂(dppz)]²⁺ Bound to RNA Mismatches

The luminescence of <i>rac</i>-[Ru­(bpy)₂(dppz)]²⁺ (bpy = 2,2′-bipyridine and dppz = dipyrido­[3,2-<i>a</i>:2′,3′-<i>c</i>]­phenazine) was explored in the presence of RNA oligonucleotides containing a single RNA mismatch (CA and GG) in order to develop a probe for RNA mismatches. While there is minimal luminescence of [Ru­(bpy)₂(dppz)]²⁺ in the presence of matched RNA due to weak binding, the luminescence is significantly enhanced in the presence of a single CA mismatch. The luminescence differential between CA mismatched and matched RNA is substantially higher compared to the DNA analogue, and therefore, [Ru(bpy)₂(dppz)]²⁺ appears to be also a sensitive light switch probe for a CA mismatch in duplex RNA. Although the luminescence intensity is lower in the presence of RNA than DNA, Förster resonance energy transfer (FRET) between the donor ruthenium complex and FRET acceptor SYTO 61 is successfully exploited to amplify the luminescence in the presence of the mismatch. Luminescence and quenching studies with sodium iodide suggest that [Ru­(bpy)₂(dppz)]²⁺ binds to these mismatches via metalloinsertion from the minor groove. This work provides further evidence that metalloinsertion is a general binding mode of octahedral metal complexes to thermodynamically destabilized mismatches not only in DNA but also in RNA

Luminescent Properties of Ruthenium(II) Complexes with Sterically Expansive Ligands Bound to DNA Defects

A new family of ruthenium­(II) complexes with sterically expansive ligands for targeting DNA defects was prepared, and their luminescent responses to base pair mismatches and/or abasic sites were investigated. Design of the complexes sought to combine the mismatch specificity of sterically expansive metalloinsertors, such as [Rh­(bpy)₂(chrysi)]³⁺ (chrysi = chrysene-5,6-quinone diimine), and the light switch behavior of [Ru­(bpy)₂(dppz)]²⁺ (dppz = dipyrido­[3,2-<i>a</i>:2′,3′-<i>c</i>]­phenazine). In one approach, complexes bearing analogues of chrysi incorporating hydrogen-bonding functionality similar to dppz were synthesized. While the complexes show luminescence only at low temperatures (77 K), competition experiments with [Ru­(bpy)₂(dppz)]²⁺ at ambient temperatures reveal that the chrysi derivatives preferentially bind DNA mismatches. In another approach, various substituents were introduced onto the dppz ligand to increase its steric bulk for mismatch binding while maintaining planarity. Steady state luminescence and luminescence lifetime measurements reveal that these dppz derivative complexes behave as DNA “light switches” but that the selectivity in binding and luminescence with mismatched/abasic versus well-matched DNA is not high. In all cases, luminescence depends sensitively upon structural perturbations to the dppz ligand