Multinuclear hafnium metal-oxo cluster, [Hf18O10(OH)26(SO4)13•(H2O)33], would be an effective heterogeneous catalyst for proteolysis specifically at aspartic acid residues (Scheme 17B, 17C). 275 there have been several reports of Hf(IV)-based MOFs as heterogeneous catalysts for organic reactions that involve activation of carbonyl groups. The Hf18 polynuclear cluster [Hf18O10(OH)26(SO4)13•(H2O)33] is insoluble in water and possesses both Lewis and Brønsted acidic moieties (i.e., protic protons of the coordinated water on the Hf centers) that was shown to facilitate hydrolysis of the amide backbones of a protein. The catalysis displayed selective cleavage at aspartate residues (both Asp-Xxx and Xxx-Asp bonds where Xxx is an arbitrary amino acid residue), and the proposed reaction mechanism is by nucleophilic attack of the aspartate COOH to the amide backbone that forms an anhydride intermediate for Xxx-Asp bond cleavage and an imide intermediate for Asp-Xxx bond cleavage, followed by another set of nucleophilic attack by a water molecule to completes the process. It should be noted that presumably due to the Brønsted acidity of the catalyst, negatively charged regions of proteins were effectively cleaved, which was not achieved with the Zr(IV)-based metal-oxo cluster catalyst. Therefore, hafnium-based catalysis may offer an alternative selectivity for proteolysis applications.