Ligand-Driven Aldehyde Condensation via Zeolitic Imidazolate Framework-Based Pro-Nanozymes with Formolase-like Activity.

The sustainable conversion of formaldehyde (FA) into high-value carbohydrate compounds via C-C condensation by formolase (FLS) is critically significant yet challenging, primarily due to its instability under high FA concentrations and its high cost. Here, we demonstrate that zeolitic imidazolate frameworks (ZIF-67 series) function as FLS-like pro-nanozymes, whose activity is initiated by water-mediated hydrolysis. This process releases metal-imidazole coordination clusters capable of catalyzing the condensation of FA and glycolaldehyde (GA) mainly into glyceraldehyde (GCA) and dihydroxyacetone (DHA) under neutral aqueous conditions. The products comprise 59% C3 carbohydrates and 41% C4 carbohydrates, with tolerance to a temperature up to 90 °C and FA concentrations up to 250 mM. Mechanism analyses demonstrate that the nucleophilicity (basicity) of N atoms in the imidazole-based ligands is critical for activating GA's α-H to form enolate anions, thereby initiating the C-C condensation with FA. The product yield and variety can be modulated by introducing different substituents into imidazole ligands and coordinating with metal ions (e.g., Zn, Co, or Ni), respectively. This work not only develops an effective strategy for rationally designing FLS-like pro-nanozymes with ZIF materials but also establishes an efficient platform for the green synthesis of multicarbon carbohydrates upon carbon recycling.