Preparation of a DFT-Designed Magnetic Molecularly Imprinted Polymers for E2 and Its Application

17β-Estradiol (E2), a potent endocrine-disrupting compound, has attracted increasing attention in food safety because trace residues in dairy products may disturb endocrine homeostasis and threaten human health. In this study, a density functional theory (DFT)-guided strategy was developed to rationally construct magnetic molecularly imprinted polymers (MMIPs) for the efficient and selective enrichment of trace E2 from complex dairy matrices. By comparing the binding energies (ΔE) of template-monomer complexes, 20 candidate functional monomers were screened, and methacrylic acid (MAA) was identified as the optimal monomer. Based on this result, core-shell MMIPs were fabricated on Fe₃O₄@SiO₂ nanoparticles via surface molecular imprinting. The prepared MMIPs exhibited high selectivity and favorable adsorption toward E2, with a maximum adsorption capacity of 25.1 mg g^-1, an equilibrium time of 30 min, and an imprinting factor of 2.88. They also showed good reusability over five cycles and satisfactory recoveries of 91.14%-95.71% in different dairy matrices. DFT analysis further revealed that multipoint hydrogen-bonding interactions between E2 and MAA played a dominant role in stabilizing the imprinted complex, with strong potential for practical dairy monitoring applications. Overall, this work provides a rational strategy for the construction of high-performance MMIPs for trace contaminant analysis in complex food matrices.