Nanozymatic Activity of UiO-66 Metal-Organic Frameworks: Tuning the Nanopore Environment Enhances Hydrolytic Activity toward Peptide Bonds

Proteolytic activity of heterogeneous Zr-based nanozymes is a promising technology for the development of selective protein cleavage protocols, which are pivotal in modern proteomics. Here, we report the hydrolytic activity of nanoporous Zr-6-based UiO-66 metal-organic framework (MOF) toward peptide bonds in a series of peptides and in hen egg-white lysozyme protein. The standard UiO-66 MOF featuring unsubstituted 1,4-benzenedicarboxylate linkers hydrolyzed the glycylglycine with a rate constant of 7.9 x 10(-7) s(-1), (t(1/2) = 10 days), which represents >10(4)-fold acceleration compared to the uncatalyzed reaction. Further, this reactivity was compared with UiO-66 analogues synthesized using modified linkers bearing NO2 and NH2 substituents, or using trifluoracetic acid as a modulator. Although the overall crystalline structure and particle size of these UiO-66 derivatives were generally conserved, they presented distinct nanoporous structures that could be directly correlated with the reaction rates at least an order of magnitude faster than that of the parent UiO-66 MOF. Further, the modified nanoporous structures also provided distinct reactivities across a series of dipeptide substrates probed. We propose that these differences might arise from the distinct MOF Lewis and Bronsted acidity resulting from the structural modifications. These findings highlight the potential of further optimizing Zr-6-based MOF nanozymes to achieve the residue-selective hydrolytic activity.