Understanding and Controlling the Selectivity of Visible Light Photocatalysis in Metal Polypyridyl Artificial Metalloenzymes

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With the support of the Chemical Catalysis Program in the Division of Chemistry, Jared C. Lewis of Indiana University is studying a new class of artificial metalloenzymes (ArMs) that promise to advance the field of photocatalysis by offering significant improvements in selectivity and function over existing technologies. The proposed ArMs incorporate synthetic catalysts that use visible light to effect a broad range of challenging chemical reactions, into protein scaffolds that will enable spatial control over the course of these reactions. As such, the designed ArM constructs will provide a unique platform to control the selectivity of reactions that are useful for chemical synthesis and potentially applicable for the manufacture of pharmaceuticals, agrochemicals, and other advanced materials. The broader impacts of the funded project will extend to an integrated outreach program focused on improving understanding of the important topic of biocatalysis among graduate, undergraduate, and high school students via innovative educational content modules. To complement this activity, a high school teacher professional development program will be developed that likewise explores the theme of biocatalysis.Understanding how enzymes can serve as hosts for different catalytic reactions and how second sphere interactions and conformational dynamics influence the properties and reactivity of metal cofactors, would greatly improve our ability to use proteins as supramolecular hosts for catalysis. Furthermore, the insights gained from such endeavors will shed light on design principles for implementing second sphere interactions more broadly in catalysis. Previous studies in the Lewis group led to the development of ArMs based on a prolyl oligopeptidase (POP) scaffold and robust methods to evolve these ArMs were identified. The work revealed that attractive interactions and conformational dynamics impact cofactor binding/bioconjugation, catalytic selectivity, and photophysical properties of metal complexes linked to POP. The funded project takes these ideas further and it will focus on the development of a new class of POP-based metal polypyridine ArMs while entailing efforts to: (a) understand metal polypyridine binding and photophysical properties within POP, (b) evolve covalent metal polypyridine ArMs for selective photoredox and energy transfer catalysis, and (c) engineer non-covalent ArMs to control the selectivity of commercially available photocatalysts. The planned research aims to illuminate on how non-covalent interactions in a conformationally dynamic protein scaffold can modulate cofactor reactivity. This approach will complement efforts in bioinorganic chemistry to model metallocofactors with static synthetic cofactor analogues or the effects of static protein scaffolds on metal ion reactivity. The potential to control the selectivity of a broad range of photoredox properties using the proposed ArMs also has the potential to significantly impact synthetic methodology. These studies will provide an ideal backdrop for improving understanding of biocatalysis at multiple levels.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.