MOF catalysis meets biochemistry: molecular insights from the hydrolytic activity of MOFs towards biomolecules

Performing reactions under physiologically relevant conditions often challenges the catalysts' robustness, reactivity and recyclability. Widely regarded as stable and versatile materials, metal-organic frameworks (MOFs) are an emerging platform for the development of materials with enzyme-like characteristics (i.e., nanozymes), whose applications in bioanalytical devices, biomolecule study, and therapeutics is attracting increasing attention. Despite these promising prospects, developing MOF-based nanozymes that operate in aqueous medium over a broad pH range, and in the presence of a high concentration of salts is frequently challenged by MOFs' low stability in water, unreliable reactivity, and favorable adsorption of substrates. In this minireview, we share detailed molecular insights on the reactivity of MOFs as nanozymes for hydrolysis reactions. Specifically, we discuss key aspects of MOF structure/activity relationship based on our recent work developing Zr-based MOF nanozymes for the hydrolysis of peptides and proteins. Further, an overview of recent works targeting the hydrolysis of other biomolecules highlighting current limitations, and promising research directions for improving the applicability of MOFs in biochemical contexts complement this analysis.