Second COordination-sphere Preorganization Effects

Objectif

SCOPE aims to quantitatively elucidate the role of substrate preorganization via chemically diverse weak interactions within the second coordination sphere (SCS), a phenomenon referred to as “substrate pre-freezing”, in modulating the reactivity and reaction outcome of C(sp3)-H bond oxidation by a bioinspired non-heme Fe(IV)=O complex. This study will provide mechanistic insight into substrate positioning effects in mononuclear iron oxygenases, a widespread enzyme superfamily central to numerous biological processes. By leveraging simplified biomimetic systems, SCOPE seeks to clarify long-standing questions regarding the structure-reactivity relationship in these enzymes and inform broader principles of catalytic efficiency. The findings may also prompt a critical reassessment of Menger’s “split-site” model of enzymatic catalysis and contribute to a more rational understanding of the design principles required for supramolecular bioinspired systems capable of performing late-stage functionalization. SCOPE is structured around three specific objectives that involve (1) synthesis and characterization of four test bench complexes followed by a quantitative analysis of substrate-complex binding interactions within the SCS. Dissecting the mechanistic role of substrate preorganization at the SCS level in (2) modulating reactivity during hydrogen atom transfer (HAT) and (3) the reaction outcome (hydroxyl rebound step) in C(sp3)-H bond oxidation. Overall, SCOPE will allow me to develop the skills and expertise necessary to establish myself as an independent researcher and a future organic chemistry professor in Europe. This fellowship will provide me with the unique opportunity to conduct cutting-edge research at the University of Basel, a leading technical institution, under the mentorship of Prof. Konrad Tiefenbacher, a rising expert in supramolecular chemistry.