Water-Soluble Mn(III)-Porphyrins with High Relaxivity and Photosensitization

Abstract

Three water-soluble Mn(III)-porphyrin complexes with cationic pyridyl side groups bearing COOH- or OH-terminated carbon chains in the meta or para positions have been synthesized as probes for both magnetic resonance imaging (MRI) and photodynamic therapy (PDT). The complexes Mn-1, Mn-2, and Mn-3 are highly water-soluble, and their relaxivities range between 10 and 15 mM-1 s-1, at 20-80 MHz and 298 K, 2-3 times higher than that of commercial Gd(III)-based agents. The complexes containing carboxylate (Mn-2) or alcoholic (Mn-3) side chains in the para position are endowed with higher relaxivities and have also shown efficient photoinduced DNA cleavage and singlet oxygen (1O2) generation. Mn-3 with stronger photoinduced DNA cleavage has also revealed stabilizing and binding activities for G4 DNA, at a similar level as the known G4 binder Mn-TMPyP4. Nevertheless, the G4-binding activity of Mn-3 was nonspecific. Preliminary tests evidenced photocytotoxicity of Mn-3 on HeLa cells without a significant effect in the absence of light. Altogether, these results underline the potential of such water-soluble Mn(III)-porphyrins for the development of multimodal approaches combining MRI and PDT.