Project Summary The family of monooxygenase enzymes are utilized to perform oxidative group transfer catalysis to broadly drive one of two functions: (1) metabolize hydrocarbon building blocks (e.g., steroids, fatty acids) for waste management or hormone synthesis in cytrochrome P450 (CYPs); and (2) the utilization of methane as the sole carbon and energy source (i.e., methanotrophic bacteria). The common trait amongst the oxidizing enzymes is the ability to electronically tune their catalytic centers to achieve oxygen transfer to robust C–H bond substrates. Adapting the electronic structure tuning principles to devise new synthetic, abiological catalysts holds great promise to (1) understand how the enzymatic systems might function by uncovering what reaction sequences are possible, and (2) developing new catalytic reactions that mimic the reactivity of the monooxygenases. This proposal describes the synthesis and characterization of novel metal-ligand multiple-bonds and metal-stabilized radicals to mimic the function of biological monooxygenases. Monooxygenases utilize metal- oxenoid ligands to drive C−H bond activation and C−heteroatom bond formation, providing a blueprint on how to emulate this reactivity. The ability to selectively incorporate functionality into unactivated C–H bonds represents a significant advance in converting inexpensive chemical feed stocks (e.g. hydrocarbons) to value-added functional molecules (e.g., pharmaceutical precursors). To achieve this goal, this proposal outlines a strategy to generate metal-ligand multiply-bonded complexes featuring oxenoid functionalities and examine their reaction chemistry as a function of transition metal and oxenoid ligand redox state. This proposal seeks to address the following questions: (1) Which transition metal-oxo linkage and attendant electronic structure can facilitate C-H bond hydroxylation chemistry? (2) Can monomeric copper support a terminal oxo-like ligand as would be suggested for the reactive oxidant in particulate methane monooxygenases? (4) How do functional group oxidation states (i.e., oxo, oxyl, oxene) impact functional group transfer catalysis? (5) Can metal-stabilized ligand radicals in general be developed to enable new C-H bond functionalization catalysis? Using dipyrrin ligand platforms as truncated models of the porphyrin platform found in cytochrome monooxygenases, this proposal outlines a strategy to synthesize and characterize metal-ligand multiple bonds on iron, cobalt, nickel, and copper. A sterically encumbered dipyrrin is proposed to be ideal for the synthesis, crystallization, and full spectroscopic characterization of a terminal oxenoid adducts of Cu akin to the potential terminal Cu(O) adduct in particulate methane monooxygenase. The broader scientific impact of the proposed research can be summarized as the following: this study will improve the field’s understanding of factors contributing to the promotion of productive C–H bond activation and fu...