Heterogeneous nanozymatic activity of Hf oxo-clusters embedded in a metal-organic framework towards peptide bond hydrolysis

Materials with enzyme-like activities and proteolytic potential are emerging as a robust and effective alternative to natural enzymes. Herein, a Hf6O8-based NU-1000 metal organic framework (Hf-MOF) is shown to act as a heterogeneous catalyst for the hydrolysis of peptide bonds under mild conditions. In the presence of Hf-MOF, a glycylglycine model dipeptide was hydrolysed with a rate constant of k(obs) = 8.33 x 10(-7) s(-1) (half-life (t(1/2)) of 231 h) at 60 degrees C and pD 7.4, which is significantly faster than the uncatalyzed reaction. Other Gly-X peptides (X = Ser, Asp, Ile, Ala, and His) were also smoothly hydrolysed under the same conditions with similar rates, except for the faster reactions observed for Gly-His and Gly-Ser. Moreover, the Hf6O8-based NU-1000 MOF also exhibits a high selectivity in the cleavage of a protein substrate, hen egg white lysozyme (HEWL). Our results suggest that embedding Hf6O8 oxo-clusters is an efficient strategy to conserve the hydrolytic activity while smoothing the strong substrate adsorption previously observed for a discrete Hf oxo-cluster that hindered further development of its proteolytic potential. Furthermore, comparison with isostructural Zr-NU-1000 shows that although the Hf variant afforded the same cleavage pattern towards HEWL but slightly slower reaction rates, it exhibited a larger stability window and a better recyclability profile. The results suggest that these differences originate from the intrinsic differences between Hf-IV and Zr-IV centers, and from the lower surface area of Hf-NU-1000 in comparison to Zr-NU-1000.

Automated summary

Materials with enzyme-like activities and proteolytic potential, such as the Hf6O8-based NU-1000 metal organic framework, are showing promise as robust and effective alternatives to natural enzymes. The Hf-MOF exhibited high selectivity in cleaving protein substrates and maintained hydrolytic activity efficiently. In comparison to the Zr-NU-1000, the Hf variant showed slightly slower reaction rates but greater stability and recyclability, attributed to intrinsic differences between Hf-IV and Zr-IV centers and the lower surface area of Hf-NU-1000.