Engineering of bioorthogonal polyzymes through polymer sidechain design

Abstract Synthetic polymer scaffolds can encapsulate transition metal catalysts (TMCs) to provide bioorthogonal nanocatalysts. These “polyzymes” catalyze the in situ generation of therapeutic agents without disrupting native biological processes. The design and modification of polymer scaffolds in these polyzymes can enhance the catalytic performance of TMCs in biological environments. In this study, we explore the hydrophobic design space of an oxanorborneneimide‐based polymer by varying the length of its carbon side chain to engineer bioorthogonal polyzymes. Activity studies indicate that modulating the hydrophobicity of the polymer scaffold can be used to enhance the catalyst loading efficacy, catalytic activity, and serum stability of polyzymes. These findings provide insight into the structural elements contributing to improving polymeric nanocatalysts for a variety of applications.