Ouzo polymerization: A bottom-up green synthesis of polymer nanoparticles by free-radical polymerization of monomers spontaneously nucleated by the Ouzo effect; Application to molecular imprinting

HYPOTHESIS: Top-down fabrication of polymer nanoparticles from preformed polymers by spontaneous colloid formation under influence of the Ouzo effect is a widely applied concept whereas bottom-up free-radical polymerization of monomers nucleated under the Ouzo regime have found limited application after a seminal report almost half a century ago. We hypothesized that the approach would be of value today as a versatile method for green synthesis of polymer nanoparticles, including molecularly imprinted ones. EXPERIMENTS: Ternary mixtures of pentaerythritol triacrylate, ethanol, and water were prepared by either a one-pot-one-step batch-wise procedure or a continuous-flow process using a 3D-printed micro-fluidic mixer. The mixtures were subjected to free-radical polymerization. Cortisol was added as a template to generate a molecular memory through molecular imprinting. Characterization of the fabricated nanoparticles was carried out by dynamic light scattering, electron microscopy, and binding studies. FINDINGS: Compositions in the Ouzo region of the ternary phase diagram provided spontaneous and instantaneous formation of nucleated monomer droplets. Free-radical polymerization, promoted by heat or UV light, transformed the droplets into polymer nanoparticles in a green and sustainable route. Addition of cortisol created polymer nanoparticles with high affinity for cortisol in aqueous media. Competition studies showed some cross-reaction with other steroids, comparable to that found with antibodies, and complete discrimination of structurally unrelated drug molecules.