Magnetic hierarchically mesoporous UIO-66(Ce/Ti) core-shell nanocomposites for efficient enrichment of phosphopeptides.

Hierarchically mesoporous metal-organic frameworks (HMUIO-66(Ce/Ti)) was designed and fabricated firstly by using a relatively rigid hydroxypropyl methylcellulose (HPMC) coupled with poly(ethylene oxide-b-propylene oxide-b-ethylene oxide, P123) as a soft template. By introducing the synergistic effect of Hofmeister ions and the soft template of HPMC coupled with P123 into the water-rich micelle system, the obtained HMUIO-66(Ce/Ti) possessed irregularly mesoporous architecture with a wide pore size distribution of 8.4 ~ 26.8 nm. Furthermore, the robust lysozyme coating layer self-organized on FeO@SiO nanoparticles readily mediated the heterogeneous nucleation and growth of MOF nanocrystals to form the magnetic hierarchically mesoporous UIO-66(Ce/Ti) core-shell nanocomposites (MHMUIO-66(Ce/Ti) CSNCs). The MHMUIO-66(Ce/Ti) CSNCs exhibited high BET surface area of 471.6 m·g with large pore volume of 0.39 cm·g, a central pore size of 13.7 nm with a wide pore size distribution of 7.8 ~ 24.5 nm, good chemical stability, and superparamagnetic properties. Consequently, the hierarchically mesoporous architecture of MHMUIO-66(Ce/Ti) CSNCs provided the high accessibility of bimetallic Ce/Ti inside binding sites and thus the enhanced phosphopeptides enrichment performance with low detection limit (0.5 fmol) and high selectivity (mass ratio of β-casein/BSA, 1:1000). Furthermore, the successful identification of 24 phosphopeptides enriched by MHMUIO-66(Ce/Ti) CSNCs from an actual sample of skim milk suggested that this method could be a good candidate for identifying phosphopeptide biomarkers in more complex biological samples.