The successful application of poly(N-vinylcaprolactam)-based microgels requires a profound understanding of their synthesis. For this purpose, a validated process model for the microgels synthesis by precipitation copolymerization with the cross-linker N,N′-methylenebis-(acrylamide) is formulated. Unknown reaction rate constants, reaction enthalpies, and partition coefficients are obtained by quantum mechanical calculations. The remaining parameter values are estimated from reaction calorimetry and Raman spectroscopy measurements of experiments with different monomer/cross-linker compositions. Because of high crosspropagation reaction rate constants, simulations predict a fast incorporation of the cross-linker. This agrees with reaction calorimetry measurements. Furthermore, the gel phase is predicted as the major reaction locus. The model is utilized for a prediction of the internal particle structure regarding its crosslink distribution. The highly cross-linked core reported in the literature corresponds to the predictions of the model.

Reversible addition−fragmentation chain transfer (RAFT) copolymerizations of methacrylic acid Nhydroxysuccinimide ester and cyclic N-vinylamide derivatives (N-vinylpyrrolidone, N-vinylpiperidone, and N-vinylcaprolactam) were successfully performed with methyl 2-(ethoxycarbonothioylthio)propanoate as chain transfer agent (CTA). Effects of different reaction parameters, such as solvent type, temperature, and CTA-to-initiator (C/I) ratio, were studied to optimize the polymerization conditions in order to obtain copolymers with variable chemical composition, controlled molecular weight, and narrow polydispersity index (PDI). The solvent type has a high impact on the polymerization reaction, and a high C/I ratio decreases polydispersity as well as conversion. Increased steric hindrance through an enlarged lactam ring offsets the monomer reactivity. The controlled character of RAFT polymerization was evidenced by the low PDI of the copolymers and a linear relationship between conversion and molecular weight. Biohybrid nanogels were synthesized by direct coupling between reactive copolymers and enhanced green fluorescent protein (EGFP) or cellulase (CelA2_M2) at room temperature in a water-in-oil emulsion. The EGFP-conjugated nanogels were fluorescent, while the CelA2_M2 encapsulated in nanogels retained its catalytic activity, as demonstrated by the hydrolysis of 4-methylumbelliferyl-β-D-cellobioside.

Microgels are commonly synthesized in batch experiments, yielding quantities sufficient to perform characterization experiments for physical property studies. With increasing attention on the application potential of microgels, little attention is yet paid to the questions (a) whether they can be produced continuously on a larger scale, (b) whether synthesis routes can be easily transferred from batch to continuous synthesis, and (c) whether their properties can be precisely controlled as a function of synthesis parameters under continuous flow reaction conditions. We present a new continuous synthesis process of two typical but different microgel systems. Their size, size distribution, and temperature-responsive behavior are compared in depth to those of microgels synthesized using batch processes, and the influence of premixing and surfactant is also investigated. For the surfactant-free poly( N-vinylcaprolactam) and poly( N-isopropylacrylamide) systems, microgels are systematically smaller, while the actual size is depending on the premixing of the reaction solutions. However, by the use of a surfactant, the size difference between batch and continuous preparation diminishes, resulting in equal-sized microgels. Temperature-induced swelling-deswelling of microgels synthesized under continuous flow conditions was similar to that of their analogues synthesized using the batch polymerization process. Additionally, investigation of the internal microgel structure using static light scattering showed no significant changes between microgels prepared under batch and continuous conditions. The work encourages synthesis concepts of sequential chemical conditions in continuous flow reactors to prepare precisely tuned new microgel systems.

Poly(N-vinylcaprolactam-co-2-methoxyethyl acrylate) core–shell microgels as imaging/diagnostic system.