DNA cleavage photoinduced by new water-soluble zinc porphyrins linked to 9-methoxyellipticine

Abstract

Two hybrid molecules based on a water-soluble zinc porphyrin covalently linked to 9-methoxyellipticine, 1 and 2, were studied as photoactivable DNA cleavers. The behaviour and efficiency of these photosensitizers were compared with the constitutive units of the hybrid molecules: meso-tetrakis(4- N-methylpyridiniumyl)porphyrinato-zinc(II) tetraacetate (ZnTMPyP, 3) and 9-methoxy- N 2methylellipticinium acetate (9-OMe-NME, 4). On irradiation at 436 nm, the efficiency of these hybrids is similar to that of ZnTMPyP and 50-fold greater than that of haematoporphyrin derivative (HPD). This photoinduced DNA cleavage is markedly reduced in the absence of oxygen and also depends on the DNA base pair to porphyrin ratio. It is inhibited by N-acetylhistidine and sodium azide, unaffected by mannitol and superoxide dismutase (SOD) and enhanced when changing H 2O for D 2O. The same scavenger effects are observed on irradiation at 514 nm. At 313 nm, the efficiency of hybrids 1 and 2 is intermediate between those of ZnTMPyP and 9-OMe-NME. In these conditions, a slight inhibitory effect of mannitol is observed, suggesting the participation of radicals probably derived from partial decomposition of the porphyrins. At these three wavelengths, singlet oxygen seems to be the main species responsible for DNA cleavage. In contrast with expectation, the great affinity of these molecules for DNA does not enhance their efficiency as DNA cleavers. This effect is discussed taking into account the long lifetime of singlet oxygen which may be generated far from the target. These molecules which are only photoactivable in the presence of DNA appear to be an efficient “molecular light switch”.