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

Abstract

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 (~10(9) 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 and Cys6 thiolates, the amino terminus and imidazole side chain of His1, and a peptide N-donor from Cys2. Over the past several years, synthetic modeling efforts by several groups have provided insight into understanding the intrinsic properties of this unusual Ni coordination site. Such analogues have revealed information regarding the (i) electrochemical properties that support Ni-based redox, (ii) oxidative protection and/or stability of the coordinated CysS ligands, (iii) probable H(+) sources for H(2)O(2) formation, and (iv) nature of the Ni coordination geometry throughout catalysis. This review includes the results and implications of such biomimetic work as it pertains to the structure and function of NiSOD.

Design and reactivity of Ni-complexes using pentadentate neutral-polypyridyl ligands: Possible mimics of NiSOD

“…2,8,9 NiSOD, the most recently discovered member of this family, was located in soil and aquatic bacteria like Streptomyces 10 and cyanobacteria, 11 and has a unique active site compared to other SOD enzymes. 12,13 The nickel center in NiSOD is coordinated in a mixed nitrogen/sulfur coordination sphere (Figure 1), and cycles through Ni(II) and Ni(III) redox states throughout the catalytic process. 13 In the reduced form, the low spin Ni(II) ion is four-coordinate and lies in a four-coordinate planar environment.…”

“…12,13 The nickel center in NiSOD is coordinated in a mixed nitrogen/sulfur coordination sphere (Figure 1), and cycles through Ni(II) and Ni(III) redox states throughout the catalytic process. 13 In the reduced form, the low spin Ni(II) ion is four-coordinate and lies in a four-coordinate planar environment. However, in the oxidized form Ni(III) is five coordinate in square pyramidal geometry, with the fifth coordination site occupied by a neighboring histidine.…”

“…19 NiSOD has an unusual anionic amide and free amine providing ligating nitrogen centers, and their relevance for controlling reactivity is not fully understood. 20 Biological reduction of superoxide to hydrogen peroxide has to be proton coupled, through one of the two possible mechanisms: a.) an inner sphere mechanism where the superoxide coordinates to the metal center and subsequently gets reduced to peroxide (or oxidized to oxygen); b.)…”

“…NiN 2 S 2 and NiN 3 S 2 complexes are either non-reactive or favor sulfur oxidation over metal mediated superoxide disproportionation when exposed to superoxides. 13,29 In some cases, it has proven possible to electrochemically generate the Ni(III) oxidation state and spectroscopically characterize that fleeting intermediate. 13,28,30–33 In our knowledge there are very few examples of low-molecular weight functional analogues of NiSOD that replicate reactivity.…”

Coordination complexes and biomolecules: A wise wedding for catalysis upgrade

“…The ultimate goal would be to select the crucial parameters for powerful catalysis, getting rid of the less pertinent ones. Such mimics (structural, functional or both) were thus developed for hydrogenases [1][2][3][4], superoxide dismutases [5][6][7][8][9], photosynthetic system [10,11], oxygenases [12] etc. These systems go from the simplest, using very usual metallic ions and ligands [13] to the most sophisticated ones [14][15][16].…”