Photodetection of DNA mismatches by dissymmetric Ru(ii) acridine based complexes

Abstract

The early detection of DNA mutations such as DNA mismatches is of major interest. Indeed, the accumulation of mismatches into the genome arises from deficiencies of the cellular mismatch repair machinery that is often associated with several types of cancers being resistant to classic chemotherapeutics. In this context, ruthenium(II) compounds bearing a planar extended ligand appear to be excellent candidates as DNA photoprobes since they exhibit high affinity for DNA as well as tuneable luminescence properties. Herein, we report on the synthesis of a novel dissymmetric acridine based Ru(II) complex, [Ru(bpy)₂napp]²⁺, along with the study of its ability to photodetect DNA mismatches. We also investigated the origin of the ability of the complex to photodetect mismatches via CD-melting assays and bio-layer interferometry. Interestingly, this behaviour may be attributed to a better protection of the excited state of the complex from non-radiative deexcitation sources (e.g., collisions with the solvent, oxygen photosensitization, etc.) when intercalated into well-matched compared to mismatched DNA.