[Ru(Me₄phen)₂dppz]²⁺, a Light Switch for DNA Mismatches

Abstract

[Ru(Me4phen)2dppz]2+ serves as a luminescent “light switch” for single base mismatches in DNA. The preferential luminescence enhancement observed with mismatches results from two factors: (i) the complex possesses a 26-fold higher binding affinity towards the mismatch compared to well-matched base pairs, and (ii) the excited state emission lifetime of the ruthenium bound to the DNA mismatch is 160 ns versus 35 ns when bound to a matched site. Results indicate that the complex binds to the mismatch through a metalloinsertion binding mode. Cu(phen)22+ quenching experiments show that the complex binds to the mismatch from the minor groove, characteristic of metalloinsertion. Additionally, the luminescence intensity of the complex with DNA containing single base mismatches correlates with the thermodynamic destabilization of the mismatch, also consistent with binding through metalloinsertion. This complex represents a potentially new early cancer diagnostic for detecting deficiencies in mismatch repair.

New Ruthenium‐Based Probes for Selective G‐Quadruplex Targeting

“…Subsequently, the discovery of the light‐switch effect of [Ru(bpy) 2 (dppz)] 2+ (dppz=dipyrido[3,2‐ a :2′,3′‐ c ]phenazine) in the presence of DNA (i.e., restoration of the luminescence of the complex upon intercalation into DNA, whereas it is not luminescent in aqueous media) marked a turning point in the field of biological application of metal complexes. The use of ruthenium(II) complexes as probes for genetic materials and cellular environment has since grown markedly and has prompted the use of other metal‐based complexes, with iridium(III), osmium(II), or rhodium(III) metal moieties, for example.…”

A Luminescent Perylenediimide as a Binding Ligand for Pyrimidine/Pyrimidine Mismatches Within a DNA Duplex

“…The melting temperatures of the 1:1 complex of PO and DNA were independent on the types of mismatched base pairs. Less stabilization by the binding of PO to the mismatch site was observed, while many MBLs are known to increase the stability of duplex structures with mismatched base pairs upon binding ,,. This is probably due to the relatively large size of the perylene ring and the substituents, causing destabilization of the local structure by steric hindrance.…”

Interfering with DNA High‐Order Structures using Chiral Ruthenium(II) Complexes

“…Recently, ruthenium(II) complexes have attracted increasing attention in the design of DNA binding and recognition agents as well as anticancer drugs targeting DNA . Some DNA intercalative Ru II complexes have been previously reported to induce DNA B–Z conformational transfer, as well as some Ru II DNA intercalating complexes, which can condense DNA .…”