Fluorophilic–Lipophilic–Hydrophilic Poly(2-oxazoline) Block Copolymers as MRI Contrast Agents: From Synthesis to Self-Assembly

Abstract

This work focuses on the synthesis and self-assembly of triphilic poly(2-oxazoline) triblock copolymers with high fluorine content toward our future aim of developing poly(2-oxazoline) magnetic resonance imaging (MRI) contrast agents. A highly fluorinated 2-substituted-2-oxazoline monomer, namely 2-(1H,1H,2H,2H-perfluorooctyl)-2-oxazoline, was synthesized using the Grignard reaction. The polymerization kinetics of the synthesized monomer was studied, and it was used for the preparation of triblock copolymers with hydrophilic 2-methyl-2-oxazoline, hydrophobic 2-octyl-2-oxazoline, and fluorophilic blocks by cationic ring-opening polymerization yielding polymers with low relatively dispersity (1.2–1.4). The presence of the blocks with the different nature in one copolymer structure facilitated self-assembly of the copolymers in water and dimethyl sulfoxide as observed by dynamic light scattering, cryo-transmission electron microscopy, and small-angle neutron scattering. The nanoparticle morphology is strongl...