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

• Published in: ACS catalysis 2023-08, Vol.13 (15), p.9918-9924
• Main Authors: Lu, Chenlin, Peng, Xue, Maity, Basudev, Sheng, Xiang, Zhou, Yinhuan, Ueno, Takafumi, Liu, Zheng, Lu, Diannan
• Format: Article
• Language: English
• ISSN: 2155-5435; 2155-5435
• DOI: 10.1021/acscatal.3c01197

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 × 103·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.