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.
