Determining the size and structure of stable and compact single chain polymeric nanoparticles prepared via different folding pathways.

We have prepared single-chain polymeric nanoparticles in water, that are folded via different pathways into particles with a structured, hydrophobic pocket: Either first non-covalent interactions followed by covalent interactions, or vice versa. The particles differ strongly in size and size stability upon solvent-switch as probed by DLS and SEC, temperature stability, and interactions with complex media. However, the in-depth determination of the size, structure, and shape was not possible by SLS and SAXS due to the small size in the former case, and scattering in SAXS only originating from the hydrophobic pocket of the particles instead of the entire particle. SANS is needed to link the precise size/shape/structure/molecular weight of the particles of the entire particle to the observed (differences in) properties.