Ionic organic cage as a versatile platform for immobilizing chemical and enzymatic sites for chemoenzymatic catalysis.

Combining the chemo- and biocatalytic sites within an integrated catalyst to orchestrate complex, multi-step reactions is highly desirable yet remains a significant challenge. Here, we introduce an ionic organic cage platform for such a chemoenzymatic catalyst, achieved by electrostatic complexation of cationic molecular cage-encapsulated Pd clusters (Pd@C-Cage) and anionic Candida antarctica lipase B. The spatial compartmentalization provided by the cage scaffold averts undesirable coordination interactions between metal and enzyme, while also facilitating substrate channelling between dual active sites in the one-pot tandem dynamic kinetic resolution of amines, resulting in 2.1-2.7 folds enhancement in product yield within the same reaction time, compared to the physical mixture of individual analogues, and even one order of magnitude higher than the mixture of commercial immobilized lipase Novozym 435 and Pd/C. Additionally, the well-defined pore aperture and charged cage skeleton enables precise microenvironment engineering of confined metal sites, providing stringent site/shape selectivity towards substrates featuring different substituents and sizes. This platform is further demonstrated by integrating other metal clusters (e.g., Ru) and enzymes (e.g., Candida antarctica lipase A, Thermomyces lanuginosus lipase, and Glucose oxidase) for a variety of chemoenzymatic reactions, with 2.1-5.3 folds enhancement compared to the physical mixture of individual analogues.