Preparation of reversed-phase/boronate affinity mixed-mode restricted access materials with zwitterionic polymer outer layers and its extraction properties.

High-selectivity and high-exclusion restricted access materials (RAMs) benefit the demands of complex biological samples. In this study, mixed-mode-adsorption RAMs bearing zwitterionic polymer brushes as their outer layers were proposed. The reversed-phase/bronate affinity (RP/BA) mixed-mode adsorption layers on the surface of the silica gel were first formed by surface-initiated atom transfer radical polymerization (SI-ATRP) employing styrene (St) and 4-vinylphenylboronic acid (4-VPBA) as comonomers Afterward, zwitterionic poly(sulfobetaine methacrylate, SBMA) was grafted via another SI-ATRP reaction to establish the external hydrophilic layer. The selectivity of the developed Sil@poly(St-co-4-VPBA)@poly(SBMA) RAMs was examined employing different analytes (benzenes, tetracyclines, neurotransmitters, β-agonists, and their structural analogs), the results revealed the preferential adsorption of substances bearing phenyl and cis-diol groups owing to the multiple interactions (hydrophobic, π-π and BA forces) caused by the RAMs with RP/BA mixed-mode adsorption mechanism. On the other hand, the synergistic effect of the strong-hydrophilicity and high-density zwitterionic poly(SBMA) could efficiently promote the exclusion of RAMs. Moreover, the experimental data revealed that > 99% of bovine serum albumin (BSA, 1 g L) could be excluded, although the tetracycline (50 µg L) was completely adsorbed, indicating the maximized adsorption capacity of the RAMs toward small molecules after the efficient exclusion of protein interference. Solid-phase extraction (SPE) employing the developed Sil@poly(St-co-4-VPBA)@poly(SBMA) RAM coupled with high-performance liquid chromatography (HPLC) was successfully employed to determine the tetracycline content of a milk sample. The established method exhibited satisfactory linearity (10-700 µg L), high recovery (93.1%-108.6%) and good precision (2.6%-8.4%). Finally, our proposed method for synthesizing RAMs could efficiently boost the adsorption selectivity and restricted access function of RAMs, thereby promoting their application in analyzing biological samples.