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.

The synthesis and characterisation of three novel iridium(III) bis‐cyclometallated complexes is reported. Their photophysics have been fully characterised by classical methods and revealed charge‐transfer (CT) and ligand‐centred (LC) transitions. Their ability to selectively interact with G‐quadruplex telomeric DNA over duplex DNA has been studied by circular dichroism (CD), bio‐layer interferometry (BLI) and surface plasmon resonance (SPR) analyses. Interestingly, one of the complexes was able to promote photoinduced electron transfer (PET) with the guanine DNA base, which in turn led to oxidative damage (such as the formation of 8‐oxoguanine) to the telomeric sequence. To the best of our knowledge, this is the first study of highly photo‐oxidising bis‐cyclometallated iridium(III) complexes with G‐quadruplex telomeric DNA.