RAFT Dispersion\nPolymerization of 2‑Hydroxyethyl\nMethacrylate in Non-polar Media

We report the reversible addition–fragmentation\nchain transfer\n(RAFT) dispersion polymerization of 2-hydroxyethyl methacrylate (HEMA)\nin <i>n</i>-dodecane using a poly(lauryl methacrylate) (PLMA)\nprecursor at 90 °C. This formulation is an example of polymerization-induced\nself-assembly (PISA), which leads to the formation of a colloidal\ndispersion of spherical PLMA–PHEMA nanoparticles at 10–20%\nw/w solids. PISA syntheses involving polar monomers in non-polar media\nhave been previously reported but this particular system offers some\nunexpected and interesting challenges in terms of both synthesis and\ncharacterization. First, GPC analysis requires chemical derivatization\nof the pendent hydroxyl groups in the PHEMA block using excess acetyl\nchloride to ensure that both blocks are fully soluble in chloroform.\nSecond, DLS, TEM and <sup>1</sup>H NMR spectroscopy studies of the\nperiodically sampled polymerizing mixture indicate the transient formation\nof anomalously large, colloidally unstable aggregates at around 50%\nconversion, which approximately corresponds to the maximum rate of\npolymerization. Remarkably, such aggregates immediately break up to\nform well-defined nanoparticles, which remain colloidally stable at\nthe end of the HEMA polymerization. Moreover, depending on the target\ndegree of polymerization (DP) for the PHEMA block, TEM studies typically\nindicate bimodal particle size distributions for PLMA–PHEMA\nnanoparticles prepared using a one-shot batch protocol. This is attributed\nto a side-reaction between HEMA monomer and the dithiobenzoate-based\nRAFT agent. Fortunately, this problem can be prevented by conducting\nsuch PISA syntheses under monomer-starved conditions by continuous\naddition of the HEMA monomer using a syringe pump. Alternatively,\nunimodal spheres can also be produced via adding HEMA in multiple\nbatches. This PISA formulation has been optimized to produce monomodal\nparticle size distributions while targeting a PHEMA DP of up to 1000\nat the maximum possible copolymer concentration. Finally, time-resolved\nsmall-angle X-ray scattering (SAXS) studies indicate the rapid formation\nof well-defined near-monodisperse spheres when targeting PLMA<sub>14</sub>–PHEMA<sub>50</sub> nanoparticles.