Time‐Resolved SAXS Studies During the Synthesis of Hydrolytically Degradable Poly(ε‐caprolactone)‐Poly( N,N′ ‐dimethylacrylamide) Diblock Copolymer Nanoparticles in Aqueous Media

Abstract The mechanism of nanoparticle formation during reverse sequence polymerization‐induced self‐assembly (PISA) is studied by small‐angle X‐ray scattering (SAXS). More specifically, N,N′ ‐dimethylacrylamide (DMAC) monomer is added to a trithiocarbonate‐capped poly(ɛ‐caprolactone) (PCL) precursor and initially polymerized in the bulk at 80 °C via reversible addition‐fragmentation chain transfer (RAFT) polymerization. SAXS indicates the unexpected formation of molten PCL droplets dispersed within DMAC monomer. After 5 min (14% DMAC conversion) at 80 °C, the reaction mixture is diluted with water, and the aqueous milieu is analyzed using a flow cell. A transient lamellar phase is formed immediately after water addition that subsequently transforms into nascent spherical nanoparticles. During the remaining DMAC polymerization, the overall nanoparticle diameter remains essentially constant with a concomitant reduction in the PCL core radius and the aggregation number. This suggests that individual PCL‐PDMAC chains are in equilibrium with the nanoparticles. SAXS analysis indicates that the amorphous PCL cores have a mean diameter of 8.8 nm at 80 °C: X‐ray diffraction (XRD) studies confirm that such nanoscale confinement prevents their crystallization on cooling to 20 °C. Finally, this formulation can be combined with crystallization‐driven self‐assembly (CDSA): UV‐initiated DMAC polymerization at 15 °C produces rod‐like PCL‐PDMAC nanoparticles with semicrystalline PCL cores.