Synthesis and Postpolymerization Modification of Fluorine-End-Labeled Poly(Pentafluorophenyl Methacrylate) Obtained via RAFT Polymerization

Chain-end-labeled polymers are interesting for a range of applications. In polymer nanomedicine, chain-end-labeled polymers are useful to study and help understand cellular internalization and intracellular trafficking processes. The recent advent of fluorescent label-free techniques, such as nanoscale secondary ion mass spectrometry (NanoSIMS), provides access to high-resolution intracellular mapping that can complement information obtained using fluorescent-labeled materials and confocal microscopy and flow cytometry. Using poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) as a prototypical polymer nanomedicine, this paper presents a synthetic strategy to polymers that contain trace element labels, such as fluorine, which can be used for NanoSIMS analysis. The strategy presented in this paper is based on reversible addition fragmentation chain transfer (RAFT) polymerization of pentafluorophenyl methacrylate (PFMA) mediated by two novel chain-transfer agents (CTAs), which contain either one (alpha) or two (alpha,omega) fluorine labels. In the first part of this study, via a number of polymerization experiments, the polymerization properties of the fluorinated RAFT CTAs were established. F-19 NMR spectroscopy revealed that these fluorinated RAFT agents possess unique spectral signatures, which allow to directly monitor RAFT agent conversion and measure end-group fidelity. Comparison with 4-cyanopentanoic acid dithiobenzoate, which is a standard CTA for the RAFT polymerization of PFMA, revealed that the introduction of one or two fluorine labels does not significantly affect the polymerization properties of the CTA. In the last part of this paper, a proof-of-concept study is presented that demonstrates the feasibility of the fluorine-labeled poly(pentafluorophenyl methacrylate) polymers as platforms for the postpolymerization modification to generate PHPMA-based polymer nanomedicines.