Dioxygenase-Reaktivität von Hämoproteinen, die mit Nicht-Hem-Eisenkatalysatoren in asymmetrischen cis-Dihydroxylierungs- und Indol-Oxidationsreaktionen rekonstituiert wurden

In nature, Rieske dioxygenases are esteemed for their proficiency in oxygenating diverse aromatic compounds, catalyzing the incorporation of molecular oxygen into various substrates. Conversely, indole and tryptophan dioxygenases specialize in the degradation of indole and tryptophan, respectively, through oxygenation reactions. By merging these enzymes, a synthetic pathway or enzymatic cascade could be engineered to efficiently metabolize indole, tryptophan, or their derivatives, generating valuable oxygenated products. Such a hybrid system holds promise for applications across biotechnology, pharmaceuticals, and environmental science, offering novel avenues for substrate conversion and product synthesis. This transformation typically involves the conversion of the aromatic indole ring to an indole-2,3- epoxide or indole-3,4-epoxide intermediate, which can subsequently react with various nucleophiles to form a wide array of products. The choice of oxidizing agents and reaction conditions greatly influence the selectivity and efficiency of this reaction, making it a subject of extensive research and development in both academic and industrial settings. This together with the ambiguity associated with the reaction mechanism for the RDO catalysed cis-dihydroxylation reactions limits the application of these enzymes in organic synthesis. Although high-valent iron-oxo and iron-dioxygen cores (e.g., iron-superoxo, iron-peroxo, and iron-hydroperoxo) are
proposed as active intermediates in many of these enzymatic reactions, the exact nature of the reactive species
has stayed elusive to date. Based on the recent discovery from the laboratory of KPI, where an iron(III)-peroxo
complex (J. Am. Chem. Soc. 2023, 145, 4389-4393; J. Am. Chem. Soc. 2024, 146, 250-262) could initiate the cisdihydroxylation of olefins and indole oxidation reactions (manuscript in preparation), this research proposal aims
to achieve the following goals, such as (1) understanding the mechanisms of nonheme catalytic systems in the
asymmetric cis-dihydroxylation of alkenes and the oxidation of indole derivatives, (2) spectroscopic characterizations and kinetics of the iron-dioxygen species (e.g., iron-superoxo, iron-peroxo, and ironhydroperoxo) based on novel ligand systems providing different steric, electronics and H-bonding effects, and (3) investigation of the performance of hemoproteins reconstituted with nonheme iron complexes as biohybrid catalysts for the cis-dihydroxylation and indole oxidation reactions.