Rationally designed mimics of antioxidant manganoenzymes: Role of structural features in the quest for catalysts with catalase and superoxide dismutase activity

Abstract

Manganese catalases (MnCAT) and superoxide dismutases (MnSOD) deplete hydrogen peroxide and superoxide in cells through a ping-pong mechanism involving cyclic oxidation and reduction of the metal cofactor. In a variety of pathological situations, the generation of reactive oxygen species overwhelms the capacity of endogenous scavengers and tissues become vulnerable to damage. Due to the limited success of the use of exogenous SOD and CAT as therapeutic agents to reduce oxidative stress damage, investigations have been directed to the design of low molecular-weight antioxidant catalysts (SOD- or CAT-mimics). To disproportionate superoxide and hydrogen peroxide efficiently, the reduction potential of MnSOD and MnCAT is fine-tuned to values much lower than that of the Mn3+(aq)/Mn2+(aq) couple. In the artificial catalysts, the number and type of ligands, the local charge, the geometry around the metal, are among the factors that introduce a way of tuning the redox potential of Mn to face redox reactions. However structural and electronic factors affecting SOD activity do not parallel those controlling CAT activity. This review focus on synthetic mononuclear Mn complexes with SOD and/or CAT activity, stressing the role of ligand donor sites, endogenous acid/base groups, metal environment and second-sphere effects in the catalytic activity.