Microcalorimetry-guided pore-microenvironment optimization to improve sensitivity of Ni-MOF electrochemical biosensor for chiral galantamine

Optimizing the microenvironment of MOF pore is an effective strategy to improve the sensitivity of MOF-based electrochemical biosensors. In this work, a series of isomorphic 3D chiral Ni-MOFs with different pore sizes were prepared and used to construct acetylcholinesterase (AChE) biosensors for the electrochemical detection of chiral drug inhibitor galantamine hydrobromide (GH). The combination of the dense metal nodes with intrinsic oxidase-like activity and the high active AChE, creates synergistic catalysis hydrolysis of acetylthiocholine chloride (ATCl) to produce fast sensing response. The more matched size and chirality of MOF pore significantly enhance the host–guest interactions between the substrate and biosensor, which allows the optimum AChE/L-Ni-BPY/DpAu/GCE platform to exhibit highly sensitive detection of GH, with a lowest detection limit of 0.31 pM and a wide linear range of 1 × 10−12 ~ 1 × 10−6 M among the reported pharmaceutical AChE inhibitor sensing systems. Such matching effect is identified and quantified with accurate apparent energy through the detailed microcalorimetry investigations, which well illustrates the structure–activity relationship of the as-synthesized biosensors. The thermodynamically-guided assembling strategy provides new insights into the development of practical MOF-based electrochemical sensors.