Synthetic Analogues of Nickel Superoxide Dismutase: A New Role for Nickel in Biology

Nickel-containing superoxide dismutases (NiSODs) represent a novel approach to the detoxification of superoxide in biology and thus contribute to the biodiversity of mechanisms for the removal of reactive oxygen species (ROS). While Ni ions play critical roles in anaerobic microbial redox (hydrogenases and CO dehydrogenase/acetyl coenzyme A synthase), they have never been associated with oxygen metabolism. Several SODs have been characterized from numerous sources and are classified by their catalytic metal as Cu/ZnSOD, MnSOD, or FeSOD. Whereas aqueous solutions of Cu(II), Mn(II), and Fe(II) ions are capable of catalyzing the dismutation of superoxide, solutions of Ni(II) are not. Nonetheless, NiSOD catalyzes the reaction at the diffusion-controlled limit (∼109 M–1 s–1). To do this, nature has created a Ni coordination unit with the appropriate Ni(III/II) redox potential (∼0.090 V vs Ag/AgCl). This potential is achieved by a unique ligand set comprised of residues from the N-terminus of the protein: Cys2 ...