Efficient Synthetic Strategies for Discrete Macromolecules: Enabling Exploration of Structure-Property Relationships in Biological and Materials Applications

Abstract

Discrete macromolecules feature precisely controlled features such as chemical composition, molecular connectivity, stereochemistry, and conformation. Compared to traditionally synthesized disperse polymers, these defined molecular features of discrete polymers offer an opportunity to explore the structure-property relations of designed polymeric systems under different applications, such as drug delivery systems and elastic materials. In this thesis, a brief introduction to the current state of macromolecular synthesis with discrete structures is first provided, including iterative linear growth (ILG) strategies, iterative exponential growth (IEG) strategies, and their direct comparison. Moreover, critical analysis of various IEG systems is then introduced, with a focus on their orthogonal chemistries of IEG cycles, structural parameters of molecular features, and advanced structures and applications. After introducing the fundamentals of discrete polymer synthesis, several works focusing on biological applications of discrete polymers are first discussed in Chapter 2 to 5. Through this IEG methodology, we prepared two series of IEG macromolecules with different stereochemistry and varied distance between stereogenic centers. After polymerizing these macromolecules using ring-opening metathesis polymerization (ROMP) to generate bottlebrush polymers with uniform arms, we evaluated their interactions with biological systems both in vitro and in vivo, which provide an optimized route for the design of future biomaterials (Chapter 2). After exploring these uniform macromolecules in a format as disperse bottlebrush polymers, we further conjugated them with site-specifically modified proteins to generate uniform polymer-protein conjugates through azide-alkyne cycloaddition reactions. These discrete conjugates eliminated manufacturing variables originating from polymer dispersity and offered more molecular features to the systems, such as absolute configurations of the polymer backbone, structural space between stereogenic centers, and sidechain functionalities. We believe that the application of discrete IEG polymers to form polymer-protein conjugates opens a new toolbox for understanding the impact of the structure of their conjugated polymers on the biological performances of proteins (Chapter 3-5). Lastly, incorporated unimolecular PDMS-functionalized spiropyran (SP) force probes into randomly-crosslinked PDMS elastomers to evaluate the force distribution in polymer networks (Chapter 6).