Ultrafast and scalable synthesis of enzyme-metal hybrid catalysts in evaporating microdroplets.

One-pot chemoenzymatic cascade reactions integrate the advantages of enzymatic catalysis and chemical catalysis, offering routes to synthesize enantiopure compounds in an efficient and environmentally friendly manner. The rational design of enzyme-metal hybrid catalysts (EMHCs) is an attractive strategy for operating chemoenzymatic cascade reactions efficiently under mild conditions. In this study, we develop a method for the instantaneous and continuous synthesis of EMHCs in evaporating microdroplets. Compared to traditional wet impregnation methods, the reaction time of the microdroplet-assisted method is shortened from days to seconds, achieving a space-time yield increase by two to five orders of magnitude. The as-prepared Pd/lipase cross-linked enzyme aggregates with ultrasmall Pd nanoclusters and well-preserved structure of enzymes exhibit excellent activity in the dynamic kinetic resolution of chiral amines. The mechanism for the process enhancement in the synthesis of EMHCs in evaporating microdroplets is studied by theoretical calculations, indicating that the fast solvent evaporation and high-heat transfer are the major factors for the instantaneous synthesis of EMHCs.