Hammett Relationship in Oxidase-Mimicking Metal–Organic Frameworks Revealed through a Protein-Engineering-Inspired Strategy

While the unique physicochemical properties of nanomaterials that enable regulation of nanozyme activities are demonstrated in many systems, quantitative relationships between the nanomaterials structure and their enzymatic activities remain poorly understood, due to the heterogeneity of compositions and active sites in these nanomaterials. Here, inspired by metalloenzymes with well-defined metal–ligand coordination, a set of substituted metal–organic frameworks (MOFs) with similar coordination is employed to investigate the relationship between structure and oxidase-mimicking activity. Both experimental results and density functional theory calculations reveal a Hammett-type structure–activity linear free energy relationship (H-SALR) of MIL-53(Fe) (MIL = Materials of Institute Lavoisier) nanozymes, in which increasing the Hammett σ_m value with electron-withdrawing ligands increases the oxidase-mimicking activity. As a result, MIL-53(Fe) NO₂ with the strongest electron-withdrawing NO₂ substituent shows a tenfold higher activity than the unsubstituted MIL-53(Fe). Furthermore, the generality of H-SALR is demonstrated for a range of substrates, one other metal (Cr), and even one other MOF type (MIL-101). Such biologically inspired quantitative studies demonstrate that it is possible to identify quantitative structure–activity relationships of nanozymes, and to provide detailed insight into the catalytic mechanisms as those in native enzymes, making it possible to use these relationships to develop high-performance nanomaterials.