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Part 1. Nickel superoxide dismutase. Part 2. Computational studies of metallothiolate complexes
Superoxide dismutases (SODs) convert the reactive superoxide molecule into oxygen and hydrogen peroxide protecting cells from reactive oxygen species. Nickel superoxide dismutase is the latest enzyme discovered in the superoxide dismutase family and represents a new class that uses a markedly different metal-ligand combination to perform its function. The enzyme is an α 6 hexamer with the active sites arranged in an octahedron separated by approximately 25 Å. Seemingly contradictory, nickel thiolates which are present in the active site are known to react with the products of the reaction, oxygen and peroxide, yet under ambient conditions they do not appear to deactivate the enzyme. The ligand environment has afforded a biologically accessible Ni(III/II) reduction potential near +300 mV vs. N.H.E. where the aqueous Ni(III/II) reduction potential is in excess of +2 V vs. N.H.E. The reduction potential is very important for reactivity with the H1Q mutation showing very little activity with a reduction potential in excess of +800 mV which is at the limit of the ability to reduce superoxide to peroxide. Some peroxide deactivation is seen in cases where the hexameric structure has been disrupted indicating stability requires the hexamer to be intact. ^ Many synthetic model systems have been developed to study various nickel enzymes such as methyl coenzyme-M reductase (MCR), NiFe hydrogenase, and NiSOD. Where synthetic studies have reached an impasse, computational studies have tested the proposed mechanisms for feasibility. These computational studies have undertaken challenges of understanding reactivity involving thiolate-oxygen chemistry and proton transfer reactions. Formation of bis-iminithiocarboxylates from the reaction of high spin Ni(II) and Zn(II) complexes of N1,N9-bis(imino-2-mercaptopropane)-1,5,9-triazanonane with oxygen was studied. The complexes react analogously but the O-O bond breaking event, determined to be the rate limiting step, involves a six coordinate intermediate for the Ni(II) complex that is not attainable in the Zn(II) case. The six coordinate intermediate lowers the energetic barrier allowing the Ni(II) complex to react at a greater rate, following the trend observed experimentally. ^
Peter A Bryngelson,
"Part 1. Nickel superoxide dismutase. Part 2. Computational studies of metallothiolate complexes"
(January 1, 2006).
Electronic Doctoral Dissertations for UMass Amherst.