Synthesis and characterization of nickel imine/amine complexes; a possible model for nickel superoxide dismutase
Superoxide dismutases are ubiquitous enzymes that efficiently catalyze the disproportionation of superoxide radical anions to protect biological molecules from oxidative damage. Several SODs have been identified having different metals at their active sites. These include Mn SOD, Fe SOD, Cu/Zn SOD and, most recently, Ni SOD. The catalytic center of Ni SOD resides in the N-terminal active-site loop, where a Ni(II) is coordinated by the amine N of His-1, the amide N of Cys-2, and two thiolate S atoms of Cys-2 and Cys-6. In the oxidized form, Ni(III) adds the imidazole N of His-1 as an axial ligand. For the past decade, we have been developing methodology using 2, 2’-dithiodibenzaldehyde (DTDB) for the synthesis of metal complexes with mixed N/S coordination. We are reporting on the application of this methodology to the synthesis of model complexes for the active site of NiSOD, in which we have successfully synthesized and characterized three NiIIN2S2 complexes of imine/amine N donors: Ni(NNS)SPh (1), Ni(NNS)SPhNO2 (2) and Ni(NNS)StBu (3). These may be used as a model for reduced NiSOD, with future plans of comparing to complexes with amide/amine N donors, thus establishing the role of the amide.
Thesis (M.S.)--Wichita State University, College of Liberal Arts and Sciences, Dept. of Chemistry