title: Synthesis of water-soluble dinuclear mn-porphyrin with multiple antioxidative activities.
abstract: 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-(N-methylpyridinium-4-yl)-10,15,20-triphenyl porphyrin (MnM4PyP3P), while gaining in catalase-like activity with its dinuclear complex, 1,3-di[5-(N-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.
authors.affiliation: Department of Applied Chemistry, Tokyo Metropolitan University , Minami-Osawa 1-1, Hachioji, Tokyo 192-0397, Japan.
authors.forename: Riku
authors.initials: R
authors.lastname: Kubota
authors.affiliation: Department of Applied Chemistry, Tokyo Metropolitan University , Minami-Osawa 1-1, Hachioji, Tokyo 192-0397, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Imamura
authors.affiliation: Department of Advanced Aging Medicine, Chiba University Graduate School of Medicine , 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Applied Chemistry, Tokyo Metropolitan University , Minami-Osawa 1-1, Hachioji, Tokyo 192-0397, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Asayama
authors.affiliation: Department of Applied Chemistry, Tokyo Metropolitan University , Minami-Osawa 1-1, Hachioji, Tokyo 192-0397, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Kawakami
keywords: Reactive oxygen species; catalase activity; dinuclear Mn-porphyrin; hydrogen peroxide; water solubility