Size-Controllable Synthesis of Uniform Spherical Covalent Organic Frameworks at Room Temperature for Highly Efficient and Selective Enrichment of Hydrophobic Peptides

Covalent organic frameworks (COFs) represent a new class of porous crystalline polymers with a diversity of applications. However, synthesis of uniform spherical COFs poses a great challenge. Here, we present size-controllable synthesis of uniform spherical COFs from nanometer to micrometer scale by a facile approach at room temperature. The as-prepared spherical COFs with different sizes exhibited ultrahigh surface area, good crystallinity, and chemical/thermal stability. Multifarious microscopic and spectroscopic techniques were performed to understand the formation mechanism and influencing factors of the spherical COFs. Moreover, the general applicability for room-temperature synthesis of the spherical COFs was demonstrated by varying different building blocks. Spherical COFs, because of the advantageous nature of their surface area, hydrophobicity, and mesoporous microenvironment, serve as an attractive restricted-access adsorption material for highly selective and efficient enrichment of hydrophobic peptides and size exclusion of macromolecular proteins simultaneously. On this basis, the spherical COFs were successfully applied to the specific capture of ultratrace C-peptide from human serum and urine samples. This research provides a new strategy for room-temperature controllable synthesis of uniform spherical COFs with different sizes and extends the application of COFs as an attractive sample-enrichment probe for clinical analysis.