Regulation of Template Ionization and Template-Monomer Interactions for Enhanced Molecular Imprinting and Selective...

A molecularly imprinted polymer (MIP)-based quartz crystal microbalance (QCM) sensor was developed for the selective detection of promethazine (PMZ) through deliberate regulation of template-monomer interactions during the molecular imprinting process. Various functional monomer systems were systematically evaluated to optimize intermolecular recognition, among which the combination of 4-vinylpyridine (4-VP) and 2-acrylamido-2-methylpropanesulfonic acid (AAMPS) exhibited the strongest interaction toward PMZ. Furthermore, protonation of PMZ using hydrochloric acid significantly enhanced electrostatic complexation between the template and functional monomers, leading to improved pre-polymerization organization, more effective imprinting-site formation and high selectivity towards target analytes. The resulting MIP-QCM sensor exhibited a linear response toward PMZ over the concentration range of 50-2000 ppb with a correlation coefficient (R²) of 0.99148 and a detection limit of 27.4 ppb. The sensor demonstrated favorable selectivity against structurally related compounds, strong anti-interference performance under highly competitive matrix conditions, and excellent regeneration stability, retaining 97.9% of its original response after ten regeneration cycles. Recovery studies in spiked tap water and carbonated beverage samples yielded recoveries ranging from 94.7% to 112.6%. These results demonstrate that regulating template ionization and template-monomer interactions is an effective strategy for improving imprinting-site quality and molecular recognition performance. The proposed approach provides new insight into the rational design of highly selective MIPs for basic pharmaceutical compounds and offers a promising platform for environmental, pharmaceutical and forensic monitoring applications.