Dummy template-assisted chiral molecularly imprinted polymer-capillary electrochromatography with synergistic...

Conventional chiral molecularly imprinted polymers (CMIPs) are constrained by the "single template-single target" recognition mode, which limits their chiral recognition spectrum. To address this issue, this study exploited the common core scaffold of β-blockers as the entry point. (S)-1-(Isopropylamino)-3-phenoxy-2-propanol (S-IPP), a byproduct of metoprolol production, was selected as a dummy template, with 4-vinylpyridine and itaconic acid synergistically employed as dual functional monomers. A dummy template-based CMIPs monolithic capillary column (DT-CMIPs@capillary) was directly prepared via in situ polymerization within the capillary, and a DT-CMIPs-CEC enantioseparation system was subsequently established. Through systematic optimization of the monolithic column preparation conditions and CEC separation parameters, enantioseparation of eight β-blockers was successfully achieved to varying degrees, with resolution values (R_S) ranging from 0.53 to 9.83 and following a clear gradient that correlated with the structural similarity of each analyte to the dummy template. This gradient was highly correlated with the structural similarity of each drug molecule, thereby validating the effectiveness of the dummy template strategy in broadening the recognition spectrum. Furthermore, static adsorption experiments were conducted to determine the selectivity factor (SF), and the correlation between SF and R_S was systematically analyzed. On this basis, a preliminary chiral recognition mechanism model was proposed from three aspects: thermodynamic selectivity, kinetic mass transfer, and structural matching integrity. This study transforms the industrial byproduct S-IPP into a functional recognition element, providing a cost-effective and broad-spectrum platform for the chiral analysis of β-blocker drugs, while also offering theoretical insights and experimental reference for the design of dummy template-based imprinted materials.