Easy access to super(19)F-labeled nanoparticles for use as MRI contrast probes via self-assembly of fluorinated copolymers synthesized by sequential RAFT polymerization

The one-pot, sequential RAFT polymerization technique was applied to the synthesis of partially fluorinated quasi-block copolymers consisting of 2,2,2-trifluoroethyl (meth)acrylate (TFE(M)A) and oligo(ethylene glycol)methyl ether (meth)acrylate (OEG sub(9)(M)A) repeating units. Starting with the polymerization of a methacrylate monomer followed by an acrylate, two sets of samples, differing mainly in terms of the distribution of hydrophobic and hydrophilic domains, were prepared, namely: POEG sub(9)MA-b-P(OEG sub(9)MA-co-TFEA)-C sub(12) (1a-e) and PTFEMA-b-P(TFEMA-co-OEG sub(9)A)-C sub(12) (2a-e). Whilst the polymers of both series lead to sub-100 nm spherical particles upon self-assembly in water, super(19)F NMR experiments revealed that the microenvironments where fluorine atoms are located in the colloids are different. Multiple super(19)F NMR peaks with low signal-to-noise ratios and large half-widths were evidenced for the nanoparticles 1a-e. In contrast, a narrow Lorentzian peak (half-width avg. = 160 Hz) with a spin-lattice relaxation time (T sub(1)) typical of micellar systems (T sub(1) avg. = 365 ms) verified the good potential of the systems 2a-e as super(19)F MRI probes when the molar fraction of the fluorinated monomer is ca. 35%. This clear structure-property relationship correlates with the complex self-assembly behavior of fluorinated amphiphilic polymers.