Metallopolymers as Functional Metalloprotein Mimics with Secondary Coordination Sphere Interactions - Project Summary/Abstract The proposed research will use synthetic organic polymers as functional mimics of protein scaffolds in metalloproteins, targeting enzyme-like reactivity that so far cannot be achieved using synthetic catalysts. We chose to mimic dopamine β-monooxygenase (DβM), an oxygenase enzyme that relies on activation of dioxygen at a copper center for its reactivity. DβM performs highly selective reactions that are both essential for human life and desirable for a range of applications from health to fuel production. In order to function effectively, the active sites of DβM and other enzymes require the microenvironment that their protein scaffold supplies, such as nearby hydrophobic or hydrophilic moieties, steric interactions, hydrogen bond donors or acceptors, and precisely tuned redox properties of the metal centers. Numerous challenges may arise when working with proteins, however, including difficulties in the synthesis of proteins on a large scale, issues with stability of some proteins (particularly membrane-bound proteins), needing to work in an aqueous environment, and limitations in modularity while maintaining an active configuration. A protein is a biopolymer, a poly(amide), with a highly controlled sequence of substituents that can be made efficiently by Nature, but is much more difficult to produce in the laboratory. The proposed work exchanges the precise poly(amide) with an easily synthesized poly(acrylate) copolymer that aims to provide the required secondary interactions for effective functionality. Studies of the poly(acrylate) frameworks will involve (1) synthesizing polymers and coordination complexes, (2) building specific polymer structures and connecting them to the coordination complexes, and (3) introducing various donors and functional groups near the metal center by varying the polymer makeup. In addition, thorough testing of the reactivity of these hybrid inorganic/polymer systems (metallopolymers) with dioxygen and subsequent oxidation activity under various conditions will be done. Ultimately, the goal of this work is to design and produce metallopolymers that will mimic enzymatic function in terms of catalytic activity, chemical selectivity, and complex stability, enabling challenging chemical transformations relevant to human health that have yet to be accomplished with a synthetic catalyst system.
