Integrated Control of the Primary and Secondary Coordination Spheres in Synthetic Monooxygenase Mimics: Probing Dioxygen Activation at a Single Metal Site.

University Of California-Irvine, Irvine CA

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Abstract

Project Summary. The proposed research plan describes the development of synthetic systems that emulate the properties found within the active sites of monooxyenases in order to probe metal-mediated activation of dioxygen. Two key design features utilized are incorporation of intramolecular hydrogen bonding (H-bond) networks within the secondary coordination sphere and the use of redox-active ligands within the primary coordination sphere. Coupling these features into a single ligand system represents an advance in molecular design that should allow for the isolation of Fe?oxo species that mimic the structures of the intermediates produced by P450 during activation of O2. This approach utilizes tridentate redox-active ligands with H-bond acceptors positioned within the secondary coordination sphere. One advantage of the approach is that additional ligands can be readily coordinated to the metal center; thus, several different variants can be prepared, characterized, and screened for function. In particular, iron complexes with axial thiolate donors are proposed that would simulate many of the structural features found within the active sites of the cyctochrome P450 monooxygenases. Similar to these enzymes, the metal ions in the proposed complexes are expected to bind and activate dioxygen (O2) to form H-bond stabilized peroxo (O22?) or oxo (O2?) units capable of functionalizing C?H bonds of substrates. Therefore, reactivity studies with O2 and hydrocarbon substrates are also proposed in which the generated products will be characterized using spectroscopic and computational techniques that include UV-vis, EPR, Mössbauer, and FTIR spectroscopies and density functional theory. These studies are expected to lead to a greater understanding of the biochemistries of monooxygenase active sites and how earth abundant metals are capable of efficiently activating C?H bonds of inert substrates.