DNA Oxidation Photoinduced by Norharmane Rhenium(I) Polypyridyl Complexes: Effect of the Bidentate N,N′‐Ligands on the Damage Profile

• Published in: Chemistry : a European journal 2018-09, Vol.24 (49), p.12902-12911
• Main Authors: Maisuls, Iván, Cabrerizo, Franco M., David‐Gara, Pedro M., Epe, Bernd, Ruiz, Gustavo T.
• Format: Article
• Language: English
• Subjects: 2,2'-Dipyridyl - chemistry; Adducts; alkaloids; Ames test; Carbolines - chemistry; Chemistry; Coordination Complexes - chemistry; Coordination Complexes - toxicity; Coordination compounds; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA adducts; DNA cleavage; DNA damage; DNA Damage - drug effects; electron transfer; Ligands; Light; Mutagenicity Tests; Organic chemistry; Oxidants, Photochemical - chemistry; Oxidation; Oxidation-Reduction; Phenazine; Photochemicals; Photosensitization; Reactive Oxygen Species - chemistry; Rhenium; Rhenium - chemistry; Salmonella typhimurium - drug effects; Singlet Oxygen - chemistry; Spectroscopy
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201801272

ReI‐polypyridyl complexes have interesting and distinctive photochemical and photosensitizing properties. This work describes the capability to induce (or photoinduce) DNA damage of three ReI‐complexes with a naturally occurring alkaloid called norharmane (nHo) as ligand: [Re(CO)3(nHo)(L)]CF3SO3 where L=2,2′‐bipyridine (ReBpy), phenanthroline (RePhen) or dipyrido[3,2‐a:2′,3′‐c]phenazine (ReDppz). The interaction of the complexes with DNA was investigated by steady‐state and time‐resolved spectroscopy. Data show that the mode and strength of interaction depend on the chemical structure of the bidentate ligand. The complexes show a major static contribution to the overall interaction, giving rise to the formation of noncovalent adducts with DNA, and the particular trend observed was RePhen>ReDppz>ReBpy. Photo‐oxidation at the purine bases represents the major DNA damaging mechanism. RePhen also induces single‐strand breaks in a yield similar to that of base damage, suggesting an additional photosensitizing pathway. We also performed the Ames test to evaluate the cytotoxic and mutagenic properties of both non‐irradiated and photoexcited complexes. RePhen, but not the other complexes, turned out to be both toxic and phototoxic for the bacteria. Illuminating DNA damage: The photosensitizing properties of three nHo‐ReI complexes (nHo=norharmane) with N,N′‐ligands is described (see figure). The interaction of the complexes with DNA was investigated by using a range of spectroscopic techniques. Quantitative DNA damage analysis shows that Re‐complexes are more efficient photosensitizers than nHo. Photo‐oxidation represents the major DNA damaging mechanism. The Ames Test showed the phototoxic and photomutagenic properties of the compounds.