Synthesis of Water-Soluble Dinuclear Mn-Porphyrin with Multiple Antioxidative Activities

Superoxide dismutase (SOD) and catalase activities of a drug are of great importance for its effective protection against reactive oxygen species (ROS)-induced injury. Achievement of catalase activity of a synthetic compound remains a challenge. Water-soluble Mn-porphyrins have high SOD and peroxynitrite (ONOO^–) reducing activities, but not catalase-like activity. Herein, we are able to retain the fair SOD-like activity of a mononuclear Mn-5-(<i>N</i>-methylpyridinium-4-yl)-10,15,20-triphenyl porphyrin (MnM4PyP₃P), while gaining in catalase-like activity with its dinuclear complex, 1,3-di­[5-(<i>N</i>-methylene-pyridinium-4-yl)-10,15,20-triphenyl porphynato manganese] benzene tetrachloride (MnPD). Mechanistic study indicates that catalase-like activity of MnPD is due to synergism of two Mn active sites, where hydroxo-Mn­(IV) complex is formed as an intermediate. The in vivo experiments demonstrate that MnPD significantly restores the treadmill-running ability of SOD-deficient mouse and thus indicates the therapeutic potential of MnPD. Furthermore, MnPD may serve as a mechanistic tool and indicate the new directions in the synthesis of catalase-like mimics