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

## TL;DR

Scientists used X-ray scattering to track how nanoparticles form during a chemical process, revealing unexpected droplet and phase changes.

## Contribution

The study reveals the mechanism of nanoparticle formation during PISA using time-resolved SAXS, including the formation of molten PCL droplets and transient lamellar phases.

## Key findings

- Molten PCL droplets form before water addition during the PISA process.
- A transient lamellar phase is observed immediately after dilution with water.
- Nanoparticle diameter remains constant while PCL core radius and aggregation number decrease.

## 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.

Synthesis of hydrolytically degradable poly(N,N′‐dimethylacrylamide)‐poly(ɛ‐caprolactone) nanoparticles via reverse sequence polymerization‐induced self‐assembly (PISA) at 80 °C is studied by time‐resolved small‐angle X‐ray scattering (SAXS). This technique reveals the formation of molten poly(ɛ‐caprolactone) (PCL) droplets prior to water addition, a transient lamellar phase, and the mechanism of growth for the final spherical block copolymer nanoparticles.