Bioinspired Model Complexes of Non-Heme Iron Enzymes: Modelling the 2-His-1-Carboxylate Facial Triad with a Family of N,N,O Phenolate Ligands

Abstract

Metal sites in biology catalyse some of the most challenging and consequential reactions on Earth, ranging from oxygen transport in animals to photosynthesis in plants and nitrogen-fixation in bacteria. This astounding breadth of reactivity includes attractive features such as small molecule activation and late-stage functionalisation, all of which are achieved under physiological conditions and with exquisite stereo- and regioselectivity. For bioinorganic chemists, the direct deployment, engineering or mimicry of metalloenzymes and metal-containing biomolecules in research and commercial applications holds great potential for improving the green credentials of today’s chemical industry. The present thesis describes the synthesis, structure and reactivity of bioinspired iron complexes that model O2-activating non-heme iron enzymes such as isopenicillin N synthase (IPNS), which contains the 2-His-1-Carboxylate facial triad (2H1C) at its active site. A family of bioinspired N,N,O phenolate ligands was developed to structurally model the 2H1C and their coordination chemistry to iron and zinc was explored. These efforts resulted in the creation of an interesting series of N,N,O-bound iron and zinc thiolate complexes that model important structural aspects of the substrate-bound active site of IPNS. This research also showed that mononuclear N,N,O-bound iron(II) alpha-ketoacid complexes could be synthesised, opening up a new field of exploration related to alpha-ketoglutarate-dependent enzymes, the largest sub-family of 2H1C-containing non-heme iron enzymes.