A\nHost–Guest Approach to Engineering Oxidase-Mimetic\nAssembly with Substrate Selectivity and Dynamic Catalysis

The\ncreation of synthetic materials that emulate the complexity\nof natural systems, such as enzymes, remains a challenge in biomimicry.\nHere, we present a simple yet effective strategy to introduce substrate\nselectivity and dynamic responsiveness into an enzyme-mimetic supramolecular\nmaterial. We achieved this by anchoring γ-cyclodextrin to a\nfluorene-modified Lys/Cu<sup>2+</sup> assembly, which mimics copper-dependent\noxidase. The binding affinity among the components was examined using <sup>1</sup>H NMR, isothermal titration calorimetry (ITC), and theoretical\nsimulation. The γ-cyclodextrin acts as a host, forming a complex\nwith the fluorenyl moiety and aromatic substrates of specific sizes.\nThis ensures the proximity of the substrate reactive groups to the\ncopper center, leading to size-selective enhancement of aromatic substrate\noxidation, particularly favoring biphenyl substrates. Notably, α-\nand β-cyclodextrins do not exhibit this effect, and the native\noxidase lacks this selectivity. Additionally, the binding affinity\nof the aromatic substrate to the catalyst can be dynamically tuned\nby adding α-cyclodextrin or by irradiating with different wavelengths\nin the presence of competitive azo-guests, resulting in switched oxidative\nactivities. This approach offers a new avenue for designing biomimetic\nmaterials with tailorable active site structures and catalytic properties.