Synthesis and reactivity of an expanded family of superoxide reductase (SOR) model complexes using N-heterocyclic, thiolate-containing ligands: Towards a better understanding of structural-functional relationships

Biomimetic chemistry remains a strong ally of enzymatic biochemistry in the role of elucidating the reaction mechanisms of metalloenzymes. Superoxide reductase (SOR) is a cysteinate-sulfur ligated non-heme iron enzyme found in anaerobes that catalyzes the one-electron reduction of the toxic superoxide radical to hydrogen peroxide. Until this date only two functional models of SOR have been reported. The work presented in this dissertation focuses on the efforts towards the synthesis of a new expanded family of SOR model complexes using N-heterocyclic ligands. The new set of complexes constitutes the first attempt of its kind at systematically understanding the relationship between structure and function in SOR biomimetic models.;A family of pyridine/quinoline based ligands has been synthesized. The N-heterocyclic ligands serve as precursors to a novel family of N4S thiolate-ligated complexes as proposed functional models of SOR. These complexes were synthesized and structurally characterized. The ligands built, systematically vary the electronics of the backbone of the complexes in order to understand the role that sterics and electronics play on potential biomimetic reactivity. Despite the minor structural differences between the various ligands, these modifications dramatically influence both structure and reactivity of the complexes.;The preliminary oxidative, biomimetic reactivity of the new set of complexes is presented. The complexes display properties directly influenced by the presence of the Lewis-acidic N-heterocyclic rings. All of the new Fe(II)-complexes in this study interact with anionic ligands including superoxide in a biomimetic fashion. In addition, reactivity has been shown between the N-aromatic based complexes and superoxide in the absence of a proton donor, unlike any other reported structural or functional model. This set of complexes expand the possibility to isolate reactive intermediates that mimic the chemistry of SOR. This structure-function study has important implications in the future design of SOR functional and structural models. Work towards the synthesis of a new family of manganese containing analogues of the iron model complexes is shown. The new manganese complexes aim at understanding the metal specificity reported for SOR. Novel reactive intermediates have been identified during reactivity screening of the thiolate-based manganese complexes towards dioxygen and superoxide.