Cluster Nuclearity Determines Substrate Adsorption/Desorption Dynamics and Peptidase Activity of UiO-66 Nanozymes

Zirconium-based metal organic frameworks (Zr-MOFs) are of great potential in catalysis due to their robustness, stability, and catalytic activity toward a broad range of reactions. Although their structure and activity could be optimized via multiple approaches, the influence of different metal-oxo cluster nuclearities has been scarcely investigated. In this work, we report on the reactivity of the dodecanuclear Zr-MOF hcp UiO-66, which features a [Zr₁₂O₂₂] cluster node instead of the ubiquitous [Zr₆O₈] found in the literature, toward the hydrolysis of peptide bonds under physiological pH conditions. This challenging reaction is of great importance in the fields of biochemistry and proteomics, where MOFs offer great potential as selective and tunable heterogeneous artificial enzymes. Using the dipeptide glycylglycine as a model substrate, we demonstrated that the Zr₁₂-based hcp UiO-66 accelerates peptide bond hydrolysis 10,000-fold with respect to the uncatalyzed reaction. Although the rate of glycylglycine hydrolysis by Zr₁₂-based UiO-66 is initially faster than that of Zr₆-based UiO-66, the dodecanuclear MOF yields an overall slower reaction by taking a longer time to afford the same reaction yield. Based on extended X-ray absorption fine structure and in situ infrared studies combined with molecular modeling, the slower conversion is caused by the strong affinity of the Zr₁₂ cluster for the product glycine. The understanding gained on the interactions of MOFs with biomolecules contributes to the development of MOF nanozymes for bioinspired applications and suggests that further optimization of the structure is needed to harvest the emerging greater reactivity of Zr₁₂ clusters.