Facile and green synthesis of a hydrophilic imprinted resin in a deep eutectic solvent–water medium for the specific molecular recognition of tumor biomarkers in complex biological matrices

Abstract

Molecularly imprinted polymers (MIPs) are highly promising materials owing to their excellent specific selectivity, chemical stability, and straightforward preparation. However, their weak molecular recognition towards target compounds and limited water compatibility restrict their application in aqueous matrices. Furthermore, most MIPs are synthesized using toxic organic reagents under harsh conditions, and their synthesis involves complicated procedures that result in environmental pollution. To address these issues associated with existing MIPs, a novel hydrophilic molecularly imprinted resin (HIR) was efficiently prepared using an environmentally friendly process that avoids the use of large quantities of hazardous organic solvents. During the synthesis, phloroglucinol was employed as a hydrophilic functional monomer to introduce abundant hydrophilic groups, hexamethylenetetramine was used as an eco-friendly cross-linking agent instead of formaldehyde, and deep eutectic solvent–water served as a green solvent. The resulting HIR exhibited outstanding molecular recognition capabilities for tumor biomarkers in the water phase owing to its synthesis in a polar system. The entire process was carried out using a mild, simple, and environmentally-friendly approach. The physical and chemical properties, adsorption capacity, and applications of the HIR were comprehensively investigated through adsorption and extraction experiments and various characterization methods. The results revealed that the HIR exhibits multiple excellent characteristics, including remarkable water compatibility, selectivity (IF = 19.2–111.6), and high adsorption capacity (35.2–50.3 mg g⁻¹) for tumor biomarkers. Notably, the HIR exhibited superior specific recognition of tumor biomarkers compared to commercial adsorbents. Furthermore, the HIR has been successfully employed to selectively extract and enrich tumor biomarkers from urine samples, demonstrating its practicality in biological and clinical applications. This study introduces a new strategy for developing green protocols to prepare water-compatible MIPs for the selective separation of tumor biomarkers from complex biological samples.