Structural and Functional Models of Non-Heme Iron Enzymes : A Study of the 2-His-1-Carboxylate Facial Triad Structural Motif

The structural and functional modeling of a specific group of non-heme iron enzymes by the synthesis of small synthetic analogues is the topic of this thesis. The group of non-heme iron enzymes with the 2-His-1-carboxylate facial triad has recently been established as a common platform for the activation of dioxygen in Nature. The oxidative transformations catalyzed by these enzymes are very diverse and many of them are unprecedented in synthetic organic chemistry. This makes this group of enzymes an attractive target for synthetic modeling studies. A new family of biomimetic N,N,O ligands that accurate model this facial triad has been developed. Structurally characterized copper complexes showed the potential of the new ligands as mimics of the facial triad. Mononuclear iron complexes of these ligands were also synthesized and in this way accurate models of the active sites of these enzymes were obtained. For instance, model complexes of the enzyme-substrate complexes of extradiol cleaving catechol dioxygenases were built and the reactivity of these complexes showed that the compounds were able to mimic the enzymes both in structure and function. Very accurate models of the closely related intradiol cleaving catechol dioxygenases were also synthesized with a slightly modified ligand system. These studies provided further insight into the factors governing the respective selectivities of these interesting enzymes. Furthermore, the reactivity of several non-heme iron complexes as oxidation catalysts was explored. Non-heme iron model complexes of the 2-His-1-carboxylate facial triad structural motif proved to be interesting oxidation catalysts and displayed both epoxidation as well as cis-dihydroxylation activity. Other catalysts showed promising reactivities in the oxidation of alkanes and alkenes. All complexes were characterized by variety of techniques including UV-Vis, IR, EPR spectroscopy, magnetic and mass spectrometric measurements, and X-ray crystal structure determinations. In the last part of the thesis, the focus is shifted to the exploration of the coordination of the new ligands with the transitions metals zinc and copper. The obtained results show that the ligands are quite versatile and interesting reactivities were discovered. The zinc complexes for instance mediate the conversion of pyruvate, an important metabolic junction, to oxalate. The copper complexes converted tetrachlorocatechol, a persistent organic pollutant, to chloranilic acid via an oxidative double dehalogenation. Both of these discovered reactivities are unprecedented.