DNA targeting by cationic porphyrin-ruthenium(II) conjugates

Abstract

Porphyrins and metalloporphyrins are investigated extensively as potential anticancer drugs. They work as DNA binding agents as well as photosensitizers in photodynamic therapy. Conjugation of the macrocycle with organometallic complexes is a powerful tool to implement the water solubility of the adducts and to provide distinct cytotoxic properties. Herein, six fourfold-symmetric cationic porphyrin-ruthenium(II) conjugates (P1-P6) are considered, which differ from one another by the substituents on the RuII fragments, the linkage of the metal fragments to the porphyrin, and the total positive charge. Their interaction with DNA sequences arranged in different conformations is investigated. The data suggest that the tested conjugates discriminate poorly between different DNA structures. Indeed, unfolded DNA works efficiently as a template for the cationic conjugates. Nevertheless, they are extremely efficient in cleaving the macromolecule upon irradiation, regardless of its structural arrangement.