Towards the Development of Photo‐Reactive Ruthenium(II) Complexes Targeting Telomeric G‐Quadruplex DNA

The design and characterization of new ruthenium(II) complexes aimed at targeting G-quadruplex DNA is herein reported. Importantly, they are based on oxidizing 1,4,5,8-tetraazaphenanthrene (TAP) ancillary ligands known to favour photo-induced electron transfer (PET) with DNA. Photochemistry of complexes 1-4 have been studied by classical methods and revealed the ability for two of them to photo-abstract an electron from guanine. From the studies of the interactions with DNA by using luminescence, circular dichroism, Bio Layer Interferometry and Surface Plasmon Resonance experiments, we demonstrated the selectivity of the complexes for telomeric G-quadruplex over duplex DNA. Preliminary biological studies of these complexes have been performed: two of them showed a remarkable photo-cytotoxicity towards telomerase negative U2OS osteosarcoma cells whereas very low mortality was observed in the dark, using the same photo-drug concentration. 2