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

Abstract

HypothesisTop-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. ExperimentsTernary 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. FindingsCompositions 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.