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

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