Bioinspired Carbonic Anhydrase Mimics with Zr–OH Sites and Size-Tunable Nanopockets for Efficient Bidirectional Catalysis of CO ₂ Hydration

Carbonic anhydrase (CA)-mimetic enzymes display promising potential in CO₂-related catalytic applications, whereas currently designed CA mimics are limited to mimicking the active site and nanopockets. Here, we report the de novo design of bioinspired Zr-OH sites and size-tunable nanopockets via Zr-organic framework structures for the efficient catalysis of CO₂ hydration and HCO₃^- dehydration. Competitive coordination modulation enhances Zr-OH site density and accessibility. The high connectivity of the ligand increases the sensitivity of the Zr-organic framework to ligand defects, while its inherently large size provides near-mesoporous-scale nanopockets. This design enables exceptional 4-nitrophenyl acetate hydrolysis performance (<i>V</i>_max = 3.86 μM s^-1 and TON = 29.92 × 10^-3 s^-1), superior to the state-of-the-art CA mimics. Meanwhile, we systematically elucidate the catalytic mechanism of Zr-OH and show that it interacts with CO₂ to form bidentate carbonate intermediates─similar to the catalytic mechanism of natural CA. Furthermore, the Zr-organic framework can also catalyze the dehydration of bicarbonate, which is consistent with the bidirectional character of natural CA. This work provides fundamental insights into the design of atomic sites and the regulation of nanopockets in enzyme mimics, as well as a promising strategy for preparing high-performance CA mimics for CO₂-related applications.