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X-ray Spectroscopic Studies of Model Compounds With Relevance to Nickel Superoxide Dismutase, Nitrile Hydratase and Copper Related Neurodegenerative Disorders
AuthorWickum, Paige Elizabeth
AdvisorShearer, Jason M.
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X-ray absorption spectroscopy (XAS) is a technique that is very useful for gaining structural and coordination information of compounds that do not crystallize. In this research a variety of bioinorganic systems were studied, each consisting of a transition metal compound that was non-crystallizable. The major goal in all projects was to determine the structure of the compounds using XAS along with many other spectroscopic techniques. The first system studied, NiSOD (nickel superoxide dismutase), was probed to determine the effects of ligand electronics on the metal center. Replacing His1 has little effect on the reduced Ni<super>II</super> form but has a significant effect on the oxidized Ni<super>III</super> form. Replacing His1 also has a significant effect on the SOD activity as the most Lewis basic donors drastically reduce the rate of O<sub>2</sub><super>·−</super> disproportionation. The next system studied, CoNHase (cobalt nitrile hydratase), was investigated to determine the active form and also the extent of oxidation of the Cys residues. A metallopeptide mimic was synthesized and then sequentially oxygenated to its active form, a sulfinate (SO<sub>2</sub>) and a sulfenic acid (SOH). Over or under oxidation result in no activity of the metellopeptide mimic. The Aβ (amyloid-β) peptide and the PrP (prion protein) were investigated to determine Cu coordination environments. The Aβ peptide forms oligomers that coordinate to Cu to produce a highly O<sub>2</sub> reactive Cu<super>I</super> center. This is very interesting due to the fact that Aβ monomers coordinate to Cu to form a neuroprotective species with very slow O<sub>2</sub> reactivity. The PrP protein was found to have a redox-inactive Cu<super>II</super>-center in the presence of Zn<super>II</super> for the normal ORP (octarepeat) domain (four repeats), however when an extra ORP was added the Cu<super>II</super>-center formed is redox-active. A DNIC (dinitrosyl iron complex) was studied and found to form a cyclic peroxynitrate in the presence of O<sub>2</sub>, which is a potent nitrating agent and also was found to give insight into a new route to generate PTN (protein tyrosine nitration). Lastly, spider and silkworm silk were investigated by designing peptide models and then incorporating Re into both our model system and native silks. By incorporating a metal center into silks the possibility for incorporating new properties into natural silks exists. In all the systems studied XAS played a large role in determining the structures of the compounds.