DNA Oxidation Photoinduced by Norharmane Rhenium(I) Polypyridyl Complexes: Effect of the Bidentate N,N'-Ligands on the Damage Profile.
Maisuls, I., Cabrerizo, F. M., David-Gara, P. M., Epe, B. and Ruiz, G. T.
Instituto de Investigaciones Biotecnologicas, Instituto de Tecnologia Chascomus (IIB-INTECH), Universidad Nacional de San Martin (UNSAM), I. Marino, Km 8.2, CC 164 (7130), Chascomus, Argentina.
Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas (INIFTA), Universidad Nacional de la Plata (UNLP), CCT La Plata-CONICET, Diag. 113y64, Suc. 4, C.C., 16 (B1906ZAA), La Plata, Argentina.
Centro de Investigaciones Opticas (CIOP-CONICET-CIC), Universidad Nacional de La Plata, C.C.3 (1897), La Plata, Argentina.
Institute of Pharmacy and Biochemistry, University of Mainz, Staudingerweg 5, D-55099, Mainz, Germany.
Re(I) -polypyridyl complexes have interesting and distinctive photochemical and photosensitizing properties. This work describes the capability to induce (or photoinduce) DNA damage of three Re(I) -complexes with a naturally occurring alkaloid called norharmane (nHo) as ligand: [Re(CO)3 (nHo)(L)]CF3 SO3 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.
Chemistry 24(49): 12902-12911 (2018)