Metal ion mediated synthesis of molecularly imprinted polymers targeting tetracyclines in aqueous samples

Molecularly imprinted polymers (MIPs) prepared in water-containing systems are more appropriate as adsorption materials in analyte extraction from biological samples. However, water as a polar solvent involved in the synthesis of MIPs frequently disrupts non-covalent interactions, and causes non-specific binding. In this study Fe2+ was used as mediator to prepare MIPs, targeting tetracyclines (TCs) of tetracycline (TC), oxytetracycline (OTC) and chlortetracycline (CTC), with TC as template molecule and methacrylic acid (MAA) as functional monomer. The subsequent binding assay indicated that Fe2+ was responsible for substantially improved specific binding in recognition of TCs by decreasing the non-specific binding. Spectrophotometric analysis suggested the existence of the strong interactions among TC, metal ions and MAA in the mixture of methanol and water. Moreover, mass spectrometric measurements verified that Fe2+ could bridge between TC and MAA to form a ternary complex of one TC, one Fe2+ and four MAAs with a mass of 844.857. Furthermore, combined with molecularly imprinted solid-phase extraction (MISPE) for sample pretreatment, HPLC–UV analysis data revealed good performance of the obtained MIPs as adsorbents. The recoveries of TC, OTC and CTC in urine samples were 80.1–91.6%, 78.4–89.3% and 78.2–86.2%, respectively. This research strategy provides an example for preparation of desirable water-compatible MIPs extracting target drugs from aqueous samples by introducing metal ion as mediator into conventional polymerization system.