Design Of Bioinspired Polymeric Chelators To Probe Metal Ion–Dependent Structure–Function Relationships

Metal recognition in proteins emerges from coordinated effects of sequence patterning, hierarchical structure, and dynamic plasticity, which together promote high-affinity, ion-selective binding. Translating these properties into synthetic polymers offers a promising route to robust and scalable materials for separations and catalysis but requires quantitative connections between copolymer features and metal-dependent behaviors that are obscured by size and sequence dispersity. Furthermore, the vast combinatorial design space accessible to synthetic copolymers presents a practical barrier to discovery of champion materials, creating a high-dimensional landscape that cannot be efficiently navigated with small-scale systematic studies.Metal-chelating polymers provide an informative testbed for probing structure-function relationships, as subtle differences in polymer structure can manifest as measurable changes in properties such as binding affinity or catalytic activity that facilitate comparisons across diverse polymer libraries. Herein, we address these challenges by developing and interrogating model polymer platforms where sequence, composition, and architecture were systematically varied to reveal how metal ions reshape macromolecule structure and function. Chapter 1 establishes a metalloprotein-inspired framework for synthetic polymer design, defining how coarse-grained sequence descriptors, hierarchical organization, and chain dynamics can be used to rationalize metal-dependent behavior in disperse copolymer systems. This framework was then applied to the design of amphiphilic polymeric chelators for lanthanide ions, demonstrating how monomer composition, patterning, and colocalization of chelating and structural moieties govern macromolecule structure, binding affinity, and selectivity across closely related ions (Chapter 2). We further explored these concepts through the development of triphenylphosphine-containing copolymers as modular scaffolds for transition metal catalysis, demonstrating how a single polymer scaffold supports multiple mechanistically distinct reactions simply through variation of the coordinated metal ion (Chapter 3). To enable systematic exploration of structure-function relationships, an automated, high-throughput platform for identifying high affinity lanthanide-binding polymers was developed by integrating automated photoinduced electron/energy transfer reversible addition–fragmentation chain-transfer (PET-RAFT) polymerization with microplate-based colorimetric binding assays (Appendix A). Finally, post-polymerization modification methods were explored as an orthogonal strategy for generating chemically diverse polymer libraries (Appendix B). Together, this framework provides a basis for developing next-generation polymeric chelators with protein-like metal recognition, critical to emerging global challenges.