Designed imidazole-based supramolecular catalysts for accelerating oxidation/hydrolysis cascade reactions

Reconstructing enzymatic active sites presents a significant challenge due to the intricacies involved in achieving enzyme-like scaffold folding and spatial arrangement of essential functional groups. There is also a growing interest in building biocatalytic networks, wherein multiple enzymatic active sites are localized within a single artificial system, allowing for cascaded transformations. In this work, we report the self-assembly of imidazole or its derivatives with fluorenylmethyloxycarbonyl-modified histidine and Cu²⁺ to fabricate a supramolecular catalyst, which possesses catechol oxidase-like dicopper center with multiple imidazole as the coordination sphere. Transmission electron microscopy, low-temperature X-band continuous-wave electron paramagnetic resonance, K-edge X-ray absorption spectra/the extended X-ray absorption fine structure analysis, and density functional theory modeling were used for the structural characterization of the catalyst. The phenol derivatives and the dissolved oxygen were used as the substrates, with the addition of 4-aminoantipyrine to generate a red adduct with a maximum absorbance at 510 nm, for obtaining time-dependent absorbance change curves and estimating the activities. The results reveal that the addition of imidazole synergistically accelerates the oxidative activity about 10-fold and the hydrolysis activity about 14-fold than fluorenylmethyloxycarbonyl modified-histidine/Cu²⁺. The supramolecular nanoassembly also exhibits the ability to catalyze oxidation/hydrolysis cascade reactions, converting 2′,7′-dichlorofluorescin diacetate into 2′,7′-dichlorofluorescein. This process can be regulated through the methylation of the imidazole component at various positions. This work may contribute to the design of advanced biomimetic catalysts, and shed light on early structural models of the active sites of the primitive copper-dependent enzymes.