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

ABSTRACT

The design and characterization of new ruthenium(II) complexes aimed at targeting G-quadruplex DNA is reported. Importantly, these complexes are based on oxidizing 1,4,5,8-tetraazaphenanthrene (TAP) ancillary ligands known to favour photo-induced electron transfer (PET) with DNA. The photochemistry of complexes 1-4 has been studied by classical methods, which revealed two of them to be capable of photo-abstracting an electron from guanine. From studies of the interactions with DNA through luminescence, circular dichroism, bio-layer interferometry, and surface plasmon resonance experiments, we have demonstrated the selectivity of these complexes for telomeric G-quadruplex DNA over duplex DNA. Preliminary biological studies of these complexes have been performed two of them showed remarkable photo-cytotoxicity towards telomerase-negative U2OS osteosarcoma cells, whereas very low mortality was observed in the dark at the same photo-drug concentration.