Discrete, Chiral Polymer-Insulin Conjugates.

Polymer conjugation has been widely used to improve the stability and pharmacokinetics of therapeutic biomacromolecules; however, conventional methods to generate such conjugates often use disperse and/or achiral polymers with limited functionality. The heterogeneity of such conjugates may lead to manufacturing variability, poorly controlled biological performance, and limited ability to optimize structure-property relationships. Here, using insulin as a model therapeutic polypeptide, we introduce a strategy for the synthesis of polymer-protein conjugates based on discrete, chiral polymers synthesized through iterative exponential growth (IEG). These conjugates eliminate manufacturing variables originating from polymer dispersity and poorly controlled absolute configuration. Moreover, they offer tunable molecular features, such as conformational rigidity, that can be modulated to impact protein function, enabling faster or longer-lasting blood glucose responses in diabetic mice when compared to PEGylated insulin and the commercial insulin variant Lantus. Furthermore, IEG-insulin conjugates showed no signs of decreased activity, immunogenicity, or toxicity following repeat dosing. This work represents a significant step toward the synthesis of precise synthetic polymer-biopolymer conjugates and reveals that fine tuning of synthetic polymer structure may be used to optimize such conjugates in the future.

Photoswitchable Sol-Gel Transitions and Catalysis Mediated by Polymer Networks with Coumarin-Decorated Cu24 L24 Metal-Organic Cages as Junctions.

Photoresponsive materials that change in response to light have been studied for a range of applications. These materials are often metastable during irradiation, returning to their pre-irradiated state after removal of the light source. Herein, we report a polymer gel comprising poly(ethylene glycol) star polymers linked by Cu24 L24 metal-organic cages/polyhedra (MOCs) with coumarin ligands. In the presence of UV light, a photosensitizer, and a hydrogen donor, this "polyMOC" material can be reversibly switched between CuII , CuI , and Cu0 . The instability of the MOC junctions in the CuI and Cu0 states leads to network disassembly, forming CuI /Cu0 solutions, respectively, that are stable until re-oxidation to CuII and supramolecular gelation. This reversible disassembly of the polyMOC network can occur in the presence of a fixed covalent second network generated in situ by copper-catalyzed azide-alkyne cycloaddition (CuAAC), providing interpenetrating supramolecular and covalent networks.

Visible-light-mediated, additive-free, and open-to-air controlled radical polymerization of acrylates and acrylamides.

Oxygen tolerance in ontrolled radical polymerizations has been an active field of study in recent years. Herein, we report a photocontrolled, additive-free iniferter polymerization that operates in completely open vials utilizing the "polymerizing through oxygen" mechanism. Trithiocarbonates are directly activated with high intensity 450 nm light to produce narrowly dispersed (M w/M n = 1.1-1.6) polyacrylates and polyacrylamides in only 1 hour of irradiation. Living behavior is demonstrated through chain extension, block copolymer synthesis, and control over molecular weight through varying the monomer:iniferter ratio. A slight increase in induction period is observed for the open vial polymerization compared to the air-free reaction, but polymers with similar M n and M w/M n values are produced after 30-60 minutes of irradiation. This system will provide a convenient platform for living additive manufacturing because of its fast reaction time, air tolerance, wide monomer scope, and lack of any additives beyond the monomer, iniferter, and DMSO solvent.