title: Manganese salen complexes with acid-base catalytic auxiliary: functional mimetics of catalase.
abstract: Antioxidant therapies have been considered for a wide variety of disorders associated with oxidative stress, and synthetic catalytic scavengers of reactive oxygen species would be clinically superior to stoichiometric ones. Among them, salen-manganese complexes (Mn(Salen)) seem promising, because they exhibit dual functions, i.e. superoxide dismutase- and catalase-mimetic activities. We have been developing enzyme-mimetic Mn(Salen) complexes bearing a functional group that enhances their catalytic activity. Here, we describe the design and synthesis of novel Mn(Salen) complexes with general acid-base catalytic functionality, inspired by the reaction mechanism of catalase. As expected, these Mn(Salen) complexes showed superior catalase-like activity and selectivity, while retaining moderate SOD-like activity. An unsubstituted pyridyl group worked well as a functionality to promote catalase-like activity. The introduced functionality did not alter the redox potential suggesting that the auxiliary-modified complex acted as an acid-base catalyst analogous to catalase. We believe that our approach provides a new design principle for sophisticated catalyst design. Further, the compounds described here appear to be good candidates for use in antioxidant therapy.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi, 467-8603, Japan.
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Noritake
authors.forename: Naoki
authors.initials: N
authors.lastname: Umezawa
authors.forename: Nobuki
authors.initials: N
authors.lastname: Kato
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Higuchi
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry; D002374:Catalase / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D045304:Cytochromes c / Q000737:chemistry; D057075:Enzyme Assays; D005029:Ethylenediamines / Q000138:chemical synthesis* / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D018716:Molecular Mimicry; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000138:chemical synthesis* / Q000737:chemistry; D013481:Superoxides / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D005029:Ethylenediamines; D009942:Organometallic Compounds; D013481:Superoxides; C090577:N,N'-bis(salicylideneamino)ethane-manganese(II); D045304:Cytochromes c; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase