Mechanistic and Spectroscopic Studies of Small Molecule Activating Enzymes and Biomimetic Model Complexes

Meeting the energy demands of an expanding human population poses significant challenges, amplified by our dependence on diminishing non-renewable resources that contribute to climate change. The potential of small molecules, especially hydrogen (H₂) and oxygen (O₂), as energy sources presents a viable alternative given their abundance and role in energy conversion. This research spotlights the role of hydrogenases and non-heme iron-containing dioxygenases in enabling small molecule activation. 

[FeFe] hydrogenases are known to catalyze H₂ generation efficiently, reaching proton reduction rates of up to 10⁴ s^-1 . This capability has prompted the development of bioinspired catalysts. Yet, current synthetic models mimicking the active center of [FeFe]-hydrogenases demonstrate far less catalytic efficiency than that of their natural counterparts. Additionally, nonheme oxygenases/oxidases, essential for activating O₂ and incorporating it into natural products, exhibit varied reactivities pivotal for numerous biological pathways. These two sets of enzymes and their corresponding model complexes are the primary focus of this thesis.

Specifically, this thesis covers analyses of tetra-iron [Fe₄] hydrogenase model complexes, where a distinctive S=1 Fe(II) intermediate spin state was identified. Our study of the kinetics and spectroscopic properties of Fe/αKG enzymes revealed novel catalytic activities and key intermediates, deepening our understanding of their mechanisms. Computational insights further highlighted factors vital to the reactivity. We also scrutinized the key substrate-triggered reactive intermediates in a non-heme di-iron enzyme of the HDOs family. Through spectroscopic studies, DFT calculations, and MD modeling, this work aspires to enhance comprehension of these enzymes, underscoring their potential in devising sustainable energy strategies.