Facile Generation of Heterotelechelic Poly(2-Oxazoline)s Towards Accelerated Exploration of Poly(2-Oxazoline)-Based Nanomedicine.

Controlling the end-groups of biocompatible polymers is crucial for enabling polymer-based therapeutics and nanomedicine. Typically, end-group diversification is a challenging and time-consuming endeavor, especially for polymers prepared via ionic polymerization mechanisms with limited functional group tolerance. In this study, we present a facile end-group diversification approach for poly(2-oxazoline)s (POx), enabling quick and reliable production of heterotelechelic polymers to facilitate POxylation. The approach relies on the careful tuning of reaction parameters to establish differential reactivity of a pentafluorobenzyl initiator fragment and the living oxazolinium chain-end, allowing the selective introduction of N-, S-, O-nucleophiles via the termination of the polymerization, and a consecutive nucleophilic para-fluoro substitution. The value of this approach for the accelerated development of nanomedicine is demonstrated through the synthesis of well-defined lipid-polymer conjugates and POx-polypeptide block-copolymers, which are well-suited for drug and gene delivery. Furthermore, we investigated the application of a lipid-POx conjugate for the formulation and delivery of mRNA-loaded lipid nanoparticles for immunization against the SARS-COV-2 virus, underscoring the value of POx as a biocompatible polymer platform.

Stoichiometric Control over Partial Transesterification of Polyacrylate Homopolymers as Platform for Functional Copolyacrylates.

Only recently, post-polymerization modification reactions of unactivated polyacrylates have been emerging as an attractive alternative to utilizing reactive monomers, enabling the synthetic upcycling of these widely applied polymers. Within this contribution, the triazabicyclodecene-catalyzed transesterification of polyacrylates is reported, including the reaction kinetics and the broad scope for macromolecular design of functional copolyacrylates. More specifically, the transesterification is performed under equilibrium conditions with a set of primary alcohols whereby the reaction kinetics and the obtained conversion as a function of stoichiometric excess of alcohol are evaluated. The results show that the obtained conversion is dependent on the polarity of the solvent and of the alcohol. Through this approach, the transesterification degree can be accurately controlled by stoichiometry, enabling the precise modulation of the macromolecular structure. Finally, the utility of this approach is demonstrated to incorporate functional side chains that are incompatible with radical polymerization, to facilitate Diels-Alder and thiol-ene reactions, enabling access to a broad range of functional materials from simple polyacrylate homopolymer precursors.