Precision-engineered artemisinin-imprinted microspheres via microfluidic-UV polymerization for enhanced separation through hydrogen-bonding and structural synergy

This study proposed an innovative strategy integrating microchannel assisted flow synthesis with UV initiated polymerization to prepare artemisinin imprinted polymers (MIPs), enabling precise control over microsphere morphology and binding site uniformity. The intermolecular hydrogen-bonding between artemisinin and functional monomers was validated via Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Photoelectron Spectroscopy (XPS), and Single Site Nuclear Magnetic Resonance (SSNMR), and was successfully engineered into the polymer microspheres. When the microsphere diameter was reduced by 50%, the adsorption capacity increased by 65%. BET results indicated that adjusting the prepolymer solvent ratio modulates the pore structure of MIP microspheres, boosting adsorption capacity by approximately 62%. Furthermore, optimizing the imprinting site precision by adjusting the crosslinker ratio elevated the selectivity factor from 1.19 to 4.46. The precisely tuned MIP demonstrated exceptional artemisinin binding capacity (up to 42.8 mg/g),3.73-fold selectivity toward artemisinin analogues, and rapid equilibrium (40 min, pseudo-second order kinetics). Notably, the microfluidically synthesized MIP retained 94% adsorption efficiency after eight regeneration cycles. Molecular simulations revealed the adsorption mechanism: customized recognition sites on the imprinted microspheres form strong hydrogen bond interactions with artemisinin. Energy difference calculations validated the correlation between simulated and actual adsorption energies, further substantiating this conclusion. This study pioneered the integration of flow chemistry and molecular imprinting technology, establishing a scalable platform for designing robust, high capacity molecularly imprinted polymers suitable for bioactive compound extraction.