Polyoxazoline-Based Bottlebrush and Brush-Arm Star Polymers via ROMP: Syntheses and Applications as Organic Radical Contrast Agents

Abstract

The synthesis of functional poly(2-alkyl-2-oxazoline) (PAOx) copolymers with complex nanoarchitectures using a graft-through ring-opening metathesis polymerization (ROMP) approach is described. First, well-defined norbornene-terminated poly(2-ethyl-2-oxazoline) (PEtOx) macromonomers (MM) were prepared by cationic ringopening polymerization. ROMP of these MMs produced bottlebrush copolymers with PEtOx side chains. In addition, PEtOx-based branched MMs bearing a terminal alkyne group were prepared and conjugated to an azidecontaining bis-spirocyclohexyl nitroxide via Cu-catalyzed azide-alkyne cycloaddition (CuAAC). ROMP of this branched MM, followed by in situ cross-linking, provided PEtOx-based brush-arm star polymers (BASPs) with nitroxide radicals localized at the core-shell interface. These PEtOx-*

Straightforward access to biocompatible poly(2-oxazoline)-coated nanomaterials by polymerization-induced self-assembly

“…12 PEtOx brush-arm star and comb-shaped polymers incorporating nitroxide radicals and perfluorinated segments, respectively, have been reported for magnetic resonance imaging. 13,14 Patterned PEtOx bottlebrush copolymer brushes on diamond were reported for biosensor design. 15 Notably, PAOx-based core-shell nanoparticles (NPs) are promising nanocarriers for biomedicine.…”

Pro-organic radical contrast agents (“pro-ORCAs”) for real-time MRI of pro-drug activation in biological systems

“…We have extensively investigated bottlebrush and related brush-arm star polymer (BASP) polymer architectures for applications in self-assembly, energy storage, drug delivery and imaging, including as ORCAs for MRI. [59][60][61][62][63][64][65][66][67][68][69][70][71] BASPs can be readily covalently conjugated to biocompatible components such as polyethylene glycol (PEG) as well as single or multiple prodrug payloads or imaging agents through the use of branched macromonomers (MMs). [59][60][61][62][63][64][65][66][67]71 PEG-based BASPs have displayed excellent safety profiles in mice and higher species, their synthesis is highly scalable and reproducible, and through MM design, the BASP prodrug activation mechanism and rate can be precisely defined.…”

An ε-caprolactone-derived 2-oxazoline inimer for the synthesis of graft copolymers

“…Bottlebrush copolymers, therefore, show advantageous features and so they have been reported extensively. 8,[14][15][16][17][18] However, the combination of 2-oxazolines and acrylates as a graft copolymer has seldom been reported, with even fewer reports on the 2-oxazoline backbone and acrylate brush combination. [19][20][21][22][23] Graft copolymers can be synthesized from three synthetic routes: grafting to, grafting through, and grafting from.…”