Title: “Water-Soluble Mn(III)-Porphyrins with High Relaxivity and Photosensitization”
Author(s): Nemeth, Tamas; Pallier, Agnes; Çelik, Çetin; garda, zoltan; Yoshizawa-Sugata, Naoko; Masai, Hisao; Tóth, Éva; Yamakoshi, Yoko
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 10-15 mM-1s-1, at 20-80 MHz and 298K, 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 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 non-specific. Preliminary tests evidenced photocytotoxicity of Mn-3 on HeLa cells without 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.
