Construction of Compartmentalized Meso/Micro Spaces in Hierarchically Porous MOFs with Long-Chain Functional Ligands Inspired by Biological Signal Amplification

The creation of spatially coupled meso-/microenvironments with biomimetic compartmentalized functionalities is of great significance to achieve efficient signal transduction and amplification. Herein, using a soft-template strategy, UiO-67-type hierarchically mesoporous metal-organic frameworks (HMMOFs) were constructed to satisfy the requirements of such an artificial system. The key to the successful synthesis of HMUiO-67 is rooted in the utilization of the preformed cerium-oxo clusters as metal precursors, aligning the growth of MOF crystals with the mild conditions required for the self-assembly of the soft template. The adoption of long-chain functional 2,2'-bipyridine-5,5'-dicarboxylic acid ligands not only resulted in larger microporous sizes, facilitating the transport of various cascade reaction intermediates, but also provided anchorages for the introduction of enzyme-mimicking active sites. A cascade amplification system was designed based on the developed HMUiO-67, in which enzyme cascade reactions were initiated and relayed by a target analyte in the separate but coupled meso/micro spaces. As a proof of concept, natural acetylcholinesterase (AChE) and Cu-based laccase mimetics were integrated into HMMOFs, establishing a spatially coupled nanoreactor. The activity of AChE was triggered by the target analyte of carbaryl, while the amplified products of AChE catalysis mediated the activity of biomimetic enzyme in the closely proximate microporous spaces, producing further amplification of detectable signal. This enabled the entire cascade system to respond to minimal carbaryl with a limit of detection as low as approximately 2 nM. Such a model of cascade amplification is expected to set a conceptual guideline for the rational design of various bioreactors, serving as a sensitive response system for quantifying numerous target analytes.