Date of Award
Ph.D. in Chemistry
Chemistry and Biochemistry
Walter E. Cleland
This research presents an investigation of synthetic model complexes with relevance to the active site of Ni(II) acireductone dioxygenase (Ni-ARD) and Ni(II) superoxide dismutase (Ni-SOD). Acireductone dioxygenases (ARDs) are a unique set of enzymes found in the methionine salvage pathway that catalyze the oxidation reaction of acireductone (1, 2-dihydroxy-3-oxo-5-(methylthio)pent-1-ene). These enzymes share a common polypeptide sequence but bind different metal ions, Ni2+ or Fe2+, at the active site. The Ni-ARD enzyme is responsible for the off pathway shunt in the pathway. Using the tridentate nitrogen donor ligands hydrotris(3,5-dimethyl-1-pyrazolyl)borate (Tp*) and the newly developed tris(1, 2-dimethyl-4-imadozyl)carbinol, (4-TICMe, Me) several reactions involving the acireductone analog 2-hydroxy-1, 3-diphenylpropan-1, 3-dione and O2 were investigated for similarities to the Ni-ARD active site. Superoxide dismutases (SODs) play a key role in protecting cells against oxidative damage by regulating the cellular concentration of the superoxide radical (O2.-) which is an unwanted byproduct of cellular metabolism. This process is accomplished by converting the superoxide radicals to hydrogen peroxide and molecular oxygen. Several small-molecule complexes were synthesized and characterized in an effort to model the reduced state of the Ni-SOD using the Tp* ligand. The structures for these complexes have been determined using X-Ray Crystallography.
Montgomery, Margo Nicole, "Synthesis And Characterization Of Nickel Complexes With Relevance To Nickel Acireductone Dioxygenase And Nickel Superoxide Dismutase" (2012). Electronic Theses and Dissertations. 417.