Metal-organic framework-mediated synthesis of hierarchical layered double hydroxide for high-efficiency enrichment of phosphopeptides

When applied as adsorbents for phosphopeptides enrichment, two-dimensional (2D) layered double hydroxides (LDHs) are usually limited by the disadvantages of buried affinity sites and reduced specific surface area. Multifarious exfoliation strategies have been implemented to compensate for these deficiencies, but tedious exfoliation process cannot meet the requirements of LDHs as high-efficiency adsorbents. Incorporating LDHs with three-dimensional (3D) template can avoid tedious exfoliation and produce hierarchical LDHs with large specific surface area and massive affinity sites. Herein, a hierarchical LDH (denoted as Fe 3 O 4 @ZIF-8@Zn–Ga LDH) was prepared by metal-organic framework (MOF)-mediated synthesis strategy, and a magnetic solid-phase extraction (MSPE) platform was constructed and employed for phosphopeptides enrichment with high efficiency. The unique 3D structure and abundant metal nodes of MOF provide 3D template and metal sources for in-situ nucleation and generation of LDH. Large specific surface area and massive exposed Zn and Ga endow Fe 3 O 4 @ZIF-8@Zn–Ga LDH with high enrichment efficiency toward phosphopeptides from complicated biological samples. With the aid of mass spectrometry (MS) techniques, we profiled endogenous or global phosphopeptides from human saliva and serum, which proved the practical application value of this material.