Importance of Thermally Induced Aggregation on ¹⁹F Magnetic Resonance Imaging of Perfluoropolyether-Based Comb-Shaped Poly(2-oxazoline)s

An understanding of thermally induced aggregation and consequent ¹⁹F magnetic resonance imaging (MRI) performance is essential for improved design of thermoresponsive ¹⁹F MRI contrast agents. Herein we describe a series of novel thermoresponsive perfluoropolyether (PFPE)-based comb-shaped poly(2-oxazoline)s (POxs) with different side-chain structures (2-methyl- (MeOx), 2-ethyl- (EtOx), and 2-( n-propyl)-2-oxazoline (nPrOx)). The comb polymers were prepared through reversible addition-fragmentation chain transfer (RAFT) polymerization of the respective oligo(2-oxazoline)acrylates using a perfluoropolyether macro-RAFT agent. The fluoropolyether chain end drives aggregation of the polymers, with small aggregates forming at 300 K for both poly(OMeOx₅A)₉-PFPE and poly(OEtOx₄A)₉-PFPE. The aggregates decrease in size and display increases in ¹⁹F MRI intensity with temperature, and at 350 K the MeOx polymers are in the form of unimers in solution, similar to the oligoethylene glycol (OEG)-based PFPE polymer. Above the T_CP of poly(OEtOx₄A)₉-PFPE, the polymer forms large aggregates, and the ¹⁹F MR imaging performance is degraded. Likewise, poly(OnPrOx₄A)-PFPE is above the LCST at all temperatures studied (300-350 K), and so weak imaging intensity is obtained. This report of novel thermoresponsive POx-based PFPE polymers highlights the importance of understanding self-association of polymers in solution and provides important insights for the development of "smart" thermoresponsive ¹⁹F MRI contrast agents.