Nickel amine/imine and amine/amide bisthiolate complexes as models for the active site of nickel superoxide dismutase

Abstract

Nickel Superoxide Dismutase (NiSOD) catalyzes disproportionation of cytotoxic superoxide radical to H2O2 and molecular O2. The mononuclear nickel center in the active site undergoes alternate oxidation and reduction during the catalytic cycle and, the coordination geometry around the Ni changes accordingly. The four-coordinate reduced state of the NiSOD is coordinated by the N-terminal amine of His1, carboxamido N of Cys2 and, two thiolato S atoms from Cys2 and Cys6 in a square-planar geometry. The oxidized state contains an additional N donor arise from the imidazole of His1 giving a five-coordinate square-pyramidal geometry. The highly unusual coordination environment of the NiSOD makes it distinct among other known SODs and motivates researchers to study about it. This research is mainly focused on to understand the role of the amide N coordination in the NiSOD which is only found in very few metalloenzymes. Through a synthetic model approach we have synthesized two types of model systems which contain amine/amide and amine/imine bisthiolate coordination. The imidazole N from His is the common N donor found in metalloenzymes and we made imine N containing models to represent the normal His imidazole N. The imine containing complexes, [Ni(NNimS]SR] were compared with the amide containing complexes, [Ni(NNamS)SR] utilizing X-ray crystallography, spectroscopic techniques, electrochemical measurements, and reactivity studies. Different thiolates with varying electron donating ability were used to study the effect of nature of the thiolates on the properties of the Ni center. This comparison allows us to understand the effective role of the amide N donation in NiSOD. In addition to our attempts at synthesizing four-coordinate NiN2S2 model complexes, this work describes our attempts at synthesizing NiN3S2 complexes as models for the oxidized state of the NiSOD.