Making imprinted polymers work in water: Engineering interfaces for better resveratrol separation

The practical application of molecularly imprinted polymers (MIPs) in aqueous separations is critically hindered by an inherent trade‐off between binding capacity and selectivity, stemming from non‐specific hydrophobic interactions. Addressing this challenge, this work establishes a robust structure–performance relationship by precisely engineering the interfacial hydrophilicity of resveratrol‐imprinted microspheres via epoxide ring‐opening. Systematically varying the modification chemistry achieved wide‐range tunability of surface wettability, with water contact angles (WCA) spanning 124.4°–19.9°. An optimal amphiphilic balance (WCA = 52.5°) using zwitterionic glycine delivered a high adsorption capacity of 43.14 mg g −1 and an imprinting factor of 2.08 under competitive aqueous conditions. Supported by molecular dynamics (MD) simulations, the optimized interface fosters a synergistic hydration shield, effectively repelling interfering species while facilitating targeted resveratrol capture. Our findings resolve the critical capacity‐selectivity paradox, providing a generalizable paradigm for developing high‐performance separation materials for complex aqueous streams in bio‐processing and pharmaceutical wastewater treatment.