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

• Published in: Chemistry : a European journal 2018-12, Vol.24 (72), p.19216-19227
• Main Authors: Weynand, Justin, Diman, Aurélie, Abraham, Michaël, Marcélis, Lionel, Jamet, Hélène, Decottignies, Anabelle, Dejeu, Jérôme, Defrancq, Eric, Elias, Benjamin
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biocompatibility; Biomedical materials; Cancer; Cell Behavior; Cell Line, Tumor; Cellular Biology; Chemical Sciences; Chemistry; Circular dichroism; Coordination chemistry; Coordination Complexes - chemistry; Cytotoxicity; Deoxyribonucleic acid; Dichroism; DNA; DNA - chemistry; DNA structures; Electron transfer; G-Quadruplexes; Guanine; Humans; Inorganic chemistry; Interferometry; Life Sciences; or physical chemistry; Osteosarcoma; Osteosarcoma - drug therapy; Osteosarcoma cells; Oxidation; photo-electron transfer; Photochemical Processes; Photochemistry; Photochemotherapy - methods; photocytotoxicity; Ruthenium; Ruthenium - chemistry; ruthenium complexes; Ruthenium compounds; Selectivity; Surface plasmon resonance; Telomerase; Telomere - chemistry; Telomere - drug effects; Theoretical and; Toxicity
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201804771

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‐ing 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. G‐quadruplex‐targeting Ru complexes: Three new photo‐oxidizing ruthenium(II) complexes based on the 2‐(4‐chlorophenyl)‐1H‐imidazo[4,5‐f][1,10]phenanthroline (CPIP) ligand have been synthesized. These complexes selectively target G‐quadruplex DNA over duplex DNA.