Novel Au(I)-Based Artificial Metallo-Cycloisomerase for Catalyzing the Cycloisomerization of gamma-Alkynoic Acids

Artificial metalloenzymes, which are designed rationally as hybrids of proteins and catalytically active transition- metal complexes, have become a promising approach for catalyzing unprecedented reactions for natural enzymes. In this study, we described the design and synthesis of an artificial metalloenzyme, a cycloisomerase that utilizes Au(I) incorporated into an apo-ferritin cage (Fr-Au) to efficiently catalyze the cycloisomerization of alkynoic acids, with a conversion of 83% and a turnover frequency of 20.6 x 10(3)center dot h(-1) in aqueous solution under mild conditions. The remarkable catalytic activity indicates that the nano-confinement of the Au(I) active site within the ferritin cage enhances its catalytic properties by stabilizing and solubilizing it. The less protected Au atom in the cysteine bridged dinuclear Au(I) active center was identified as critical for the Fr-Au cycloisomerases to catalyze this reaction. In addition, we provide insight into the catalytic mechanism through quantum chemical (QC) calculations, which reveal an energy barrier of 32.29 kJ/mol.

Automated summary

Artificial metalloenzymes, designed as hybrids of proteins and catalytically active transition-metal complexes, show great potential in catalyzing new reactions. In this study, an artificial metalloenzyme, a cycloisomerase utilizing Au(I) incorporated into an apo-ferritin cage (Fr-Au), was successfully synthesized and demonstrated efficient catalysis of alkynoic acid cycloisomerization under mild conditions in aqueous solution. The high catalytic activity is attributed to the nano-confinement effect of the ferritin cage, which stabilizes and solubilizes the Au(I) active site. Quantum chemical calculations provided insight into the catalytic mechanism, revealing an energy barrier of 32.29 kJ/mol.