Efficient Route to Compact Single-Chain Nanoparticles: Photoactivated Synthesis via Thiol–Yne Coupling Reaction

We report a new strategy for the rapid, efficient synthesis of single-chain polymer nanoparticles (SCNPs) having a nearly globular morphology in solution, by employing photoactivated radical-mediated thiol–yne coupling (TYC) reaction as the driving force for chain folding/collapse. Confirmation of SCNP formation was carried out by means of a combination of complementary experimental techniques. Size exclusion chromatography (SEC), small-angle X-ray scattering (SAXS), and dynamic light scattering (DLS) measurements revealed a considerable degree of compaction of the resulting SCNPs. This finding was confirmed by molecular dynamics (MD) simulations. The analysis of the scattering form factors provided by SAXS revealed a scaling exponent ν ≈ 0.37 for the dependence of the SCNP size on its molecular weight. This value is close to that expected for globular objects, ν = 1/3, and much smaller than the usual observation (ν ≈ 0.5) for SCNPs synthesized with most of the state-of-the-art techniques, which instead show sparse morphologies. Insight into the physical origin of this fundamental difference with standard SCNPs was obtained from molecular dynamics simulations. Namely, intrachain bonding mediated by relatively long cross-linkers combined with the use of bifunctional groups in the SCNP precursor largely increases the probability of forming long-range loops which are efficient for global chain compaction.