Peptide bond hydrolysis catalyzed by NU-1000 MOF revealed key structural features that influence the catalytic performance of Zr₆ based MOFs.

Peptide bond formation is a challenging, environmentally and economically demanding transformation.Catalysis is key to circumvent current bottlenecks. To date, many homogeneous catalysts able to provide synthetically useful methods have been developed, while heterogeneous catalysts remain largely restricted to the studies addressing the prebiotic formation of peptides. Here, the catalytic activity of Zr6-based metalorganic frameworks (Zr-MOFs) towards the peptide bond formation is investigated using the dipeptide cyclization as a model reaction. Unlike previous catalysts, Zr-MOFs largely tolerate water, and reactions are carried out under ambient conditions. Notably, the catalyst is recyclable and no additives to activate COOH group are necessary, which are common limitations of previous methods. In addition, broad reaction scope tolerates substrates with bulky and Lewis basic groups. The reaction mechanism was assessed by intermolecular peptide bond formation. While intrinsic challenges associated with the catalyst structure and water removal limit a more general intermolecular reaction scope under current conditions, the results suggest that further design of Zr-MOF catalysts could render these materials broadly useful as heterogeneous catalysts for this challenging transformation.

The catalytic activity of metal−organic frameworks (MOFs) toward peptides and proteins provides an attractive route for the development of nanozymes for applications in biotechnology and proteomics, particularly in the field of protein identification using mass spectrometry. Here, we report that carefully tuning the Ce/Zr metal ratio is a promising strategy to overcome structural limitations that originate from the high connectivity of the Zr 6 node and also increase the peptidase activity of the MOF while preserving the material's nano-topology and stability. A series of bimetallic Ce/Zr-UiO-66 MOFs, in which the amount of Ce was systematically varied from 28 to 87 mol%, have been shown to efficiently catalyze peptide bond hydrolysis in a large variety of peptides with different functional groups, demonstrating their nanozyme potential. Detailed kinetic analysis of the hydrolysis of peptide bonds with a range of Ce/Zr MOFs suggests that among the different metallic clusters present in UiO-66, the Ce 6 clusters have superior reactivity compared to the CeZr 5 sites. In addition to increasing the catalytic potency of the MOF toward peptide bond hydrolysis, the introduction of Ce(IV) also broadens the reaction scope of MOF catalysts. Selective oxidation of the thiol sidechains and the formation of disulfide bridges have been observed at physiological pH both in cysteine and in glutathione tripeptide as substrates. The rate of oxidation is directly proportional to the amount of Ce present in the MOF, demonstrating that the introduction of Ce into these nanomaterials is a promising strategy to introduce oxidase activity toward biologically relevant substrates. In addition to this, adsorption of dipeptides onto MOF nanomaterials has been studied for the first time. These studies revealed a close link between the nature of peptide side chains and the extent of their adsorption, which has a direct influence on their ability to act as substrates in MOF-catalyzed reactions.

The proteolytic activity of materials with enzyme-like activities is emerging as a robust, and effective alternative to natural enzymes. Herein, Hf6O8-based NU-1000 metal organic framework (Hf-MOF) is shown to act...

Fundamental insight into the interactions between biological molecules and materials is essential for the design and development of adsorbents for many applications. Herein, we use a range of peptides to...