To explore a clear formation mechanism of a three-dimensional (3D) bicontinuous skeleton and control the structure of an epoxy-based monolith, we have prepared the monolith using a mixture of good and poor solvents. The influences of reaction and phase separation parameters, such as molecular weights and content of porogenic poor solvents, porogenic good solvent concentration, equivalent ratio of epoxy group to amine and reaction temperature on the final morphology are systematically studied by monitoring the reaction process with differential scanning calorimetry (DSC) and observing the cloud points (CP). Depending on the above parameters, the resultant morphology can be varied ranging from closed pore structure to globules aggregated structure, which was controlled by the competitive kinetics between the domain coarsening and the structure freezing. The optimized monoliths with uniform and controllable pores have great potential for application in chromatographic separation, membrane filters, and membrane emulsification.

•The polymer monolith for solid-phase peptide synthesis was prepared by AGET ATRP of PEGA.•A continuous flow technique was designed for solid-phase peptide synthesis.•The grafting PPEGA increased the loading capacity of the monolith in the range of 0.32–0.85 mmol/g.•The grafted monolith gave 92% purity of the crude ACP 65–74.•The grafted monolith gave 4–5 folds higher than Wang resins in synthesis efficiency.The polymer monolith for solid-phase synthesis was prepared through in situ copolymerization of chloromethylstyrene and ethylene glycol dimethacrylate (PCMS-EDMA), and the obtained monolith was grafted by poly (ethylene glycol) acrylate monomer via activators generated by electron transfer atom transfer radical polymerization (AGET ATRP). The novel monolith was highly crosslinked and showed no detectable swelling in both polar and nonpolar solvents (e.g. dichloromethane, dimethylformamide, tetrahydrofuran, acetonitrile, and methanol). The grafted monolith increased the number of functional groups in the range of 0.32–0.85 mmol/g, which resulted from side groups in each grafting polymer chain. Meanwhile, the grafted monolith showed good permeability and mechanical strength under the flow-through conditions. This monolith was derived into Wang resin and used in the synthesis of a difficult sequence-acyl carrier protein fragment 65–74 (ACP 65–74) in a new designed continuous flow equipment. The yield and purity of the crude peptide acquired from the grafted monolith reached 82% and 92%, respectively, which were higher than those by the ungrafted monolith (51% and 60%, respectively) or commercial Wang resin (51% and 61%, respectively). The synthetic efficiency on the grafted monolith in the continuous flow technique was 4–5 folds higher than on Wang resins in the manually operation conditions. Therefore, this monolithic resin showed potential effects in production scale-up.

The polymer monolith for solid-phase synthesis with high efficiency was prepared through in situ copolymerization of chloromethylstyrene and ethylene glycol dimethacrylate (PCMS–EDMA). The obtained monolith was grafted by two kinds of poly(ethylene glycol) acrylate oligomer, poly(ethylene glycol) acrylate (PEGA) and poly(ethylene glycol) methyl ether acrylate (mPEGA). The monolith was grafted via activators generated by electron transfer atom transfer radical polymerization (AGET ATRP) with the increased number of functional groups (–OH). About 0.61–0.81 mmol/g hydroxyl group resulted from side groups in each grafting polymer chain. PmPEGA in the grafting block copolymer chains can increase the distance between the adjacent reactive sites of PEGA (–OH) in each polymer chain. Therefore, the grafted monoliths with the block copolymer of PEGA-co-mPEGA can give high yield (85%) and purity (93%) of the crude peptide (a difficult sequence-acyl carrier protein fragment 65–74) under the condition of high loading capacity (0.76 mmol/g). These results were higher than those by the grafted monolith with only polymer of PEGA (72% and 81%, respectively) and commercial Wang resin (43% and 39%, respectively). The synthetic efficiency on the grafted monolith with block copolymer in the continuous flow technique was 5–6 folds higher than Wang resins in the manual operation conditions.