Polyol-Assisted Aqueous Synthesis of HKUST-1 Enables Direct Protein Encapsulation

A polyol-assisted method enables the aqueous synthesis of hydrolytically unstable HKUST-1. The use of polyols as co-solvent—particularly glycerol—promotes the formation of high-quality crystalline materials, while allowing tunable control over particle size through adjustment of the initial reagent concentration. This approach enhances the water tolerance of HKUST-1 by stabilizing the Cu(II) paddlewheel and is fully compatible with in situ protein encapsulation. The method has been successfully applied to a variety of proteins with different electrostatic properties, yielding protein@HKUST-1 biocomposites that retain structural integrity and enzymatic activity over multiple cycles. These findings provide a mild, biocompatible route for producing water-stable MOFs and MOF-based biocomposites, expanding their potential for biotechnological and biomedical applications.