A combination of distillation-precipitation polymerization and click chemistry: fabrication of boronic acid functionalized Fe3O4 hybrid composites for enrichment of glycoproteins

Biomedical sciences, and in particular biomarker research, demand efficient glycoprotein enrichment platforms. In this paper, a facile and efficient approach combining distillation-precipitation polymerization (DPP) and click chemistry was developed to synthesize boronic acid ligand-modified magnetic nanoparticles for the enrichment of glycoproteins. Due to the relatively large amount of benzyl chloride groups introduced by DPP on the magnetic core, which easily can be transferred into azide groups, the alkyne-phenylboronic acid ligands were immobilized onto the surface of Fe3O4 with high efficiency via the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) 'click' reaction. The morphology, structure and composition of the resulting core-shell Fe3O4@poly(4-vinylbenylchloride)@amidophenylboronic acid (Fe3O4@pVBC@APBA) nanocomposites were characterized by transmission electron microscopy, X-ray powder diffraction, vibrating sample magnetometry, Fourier transform infrared spectroscopy, thermogravimetric analysis and X-ray photoelectron spectrometry. The Fe3O4@pVBC@APBA microspheres held a similar to 50 nm polymeric shell, and exhibited high magnetic response to an external magnetic field. The binding results demonstrated that Fe3O4@pVBC@APBA possessed high adsorption capacity and remarkable selectivity to glycoproteins. Moreover, the glycoproteins in the egg white sample could be enriched under physiological conditions (pH 7.4) as well, due to the lower pK(a) value of the alkyne-phenylboronic acid ligand. The high stability and selectivity of Fe3O4@pVBC@APBA for the glycoproteins were retained over several separation cycles. This boronate affinity material has potential applications in biomedical and biotechnological fields including drug delivery and biosensing.