An alkali-resistant zirconium-biligand organic framework with dual-metal centers for highly selective capture of phosphopeptides.

The stability of MOFs plays one of the most important roles in material applications, while the delicate structure of MOFs suffers from the limitation of poor alkali tolerance. A new biligand Zr-MOF (biUIO-66-NHNO) with alkali-resistance performance and active functional groups has been synthesized in this study. The biUIO-66-NHNO demonstrated a much better stability in 1% NH·HO solution than its parent material, UIO-66-NH. Following further immobilization of Zr ions, the biDZMOF consisting of dual-zirconium centers was prepared and was further applied in global enrichment of phosphopeptides by avoiding the instability of enrichment materials in the essential alkali elution procedure for the phosphopeptide enrichment workflow. The alkali-resistant elution of phosphopeptides from the biDZMOF can be directly coupled to a tandem mass spectrometry system for peptide analysis without desalting treatment. 425 phosphopeptides in total in 3 independent samples were identified from 10 μL human saliva after enrichment with biDZMOF. The improvement in alkali resistance and successful post-modification of biUIO-66-NHNO suggest an efficient strategy to develop new types of MOF materials for application.