Dynamic Metal–Organic Tweezer Enables High-Resolution Nanopore Analysis of Steroid Hormones

Abstract The utilization of host–guest chemistry stands as a classic strategy in nanopore technology to refine detection capabilities. However, the current efforts are limited to natural supramolecular hosts with rigid and toroidal structures (e.g., cyclodextrin, cucurbituril), which can present structural constraints when accommodating larger or variable analytes. Herein, we develop a type of dynamic and pincer-like supramolecular host, metal–organic tweezers (MOTs), providing an adaptable host-assisted platform to improve molecular resolution in nanopore analysis. Unlike traditional hosts, open-style MOTs feature highly adaptable structures, in which the dihedral angle between the tweezer’s two ends dynamically adjusts in response to the analyte. This renders the efficient encapsulation of analyte molecules with varying sizes and configurations through host–guest interactions and the generation of distinctive fingerprint signals within the α-HL nanopore system. By optimizing the organic palladium centers and imidazole-containing ligands in MOTs, we have successfully discriminated a range of steroid hormones that play crucial roles in physiological processes like reproductive regulation, substance metabolism, or stress responses. Notably, the MOTs-assisted nanopore also achieves the quantitative detection of natural progesterone in simulated plasma, demonstrating its potential applicability in complex biological matrices as a promising bioanalytical tool.