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

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 <b>Mn-1</b>, <b>Mn-2</b>, and <b>Mn-3</b> 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 (<b>Mn-2</b>) or alcoholic (<b>Mn-3</b>) side chains in the para position are endowed with higher relaxivities and have also shown efficient photoinduced DNA cleavage and singlet oxygen (¹O₂) generation. <b>Mn-3</b> with stronger photoinduced DNA cleavage has also revealed stabilizing and binding activities for G4 DNA, at a similar level as the known G4 binder <b>Mn-TMPyP4</b>. Nevertheless, the G4-binding activity of <b>Mn-3</b> was nonspecific. Preliminary tests evidenced photocytotoxicity of <b>Mn-3</b> 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.