Pore‐Engineered Hydrogen‐Bonded Supramolecular Fluorosensor for Ultrasensitive Determination of Copper Ions

Abstract The selective quantification of copper ions (Cu 2+ ) in biosamples holds great importance for disease diagnosis, treatment, and prognosis since the Cu 2+ level is closely associated with the physiological state of the human body. While it remains a long‐term challenge due to the extremely low level of free Cu 2+ and the potential interference by the complex matrices. Here, a pore‐engineered hydrogen‐bonded organic framework (HOF) fluorosensor is constructed enabling the ultrasensitive and highly selective detection of free Cu 2+ . Attributing to atomically precise functionalization of active amino “arm” within the HOF pores and the periodic π‐conjugated skeleton, this porous HOF fluorosensor affords high affinity toward Cu 2+ through double copper–nitrogen (Cu─N) coordination interactions, resulting in specific fluorescence quenching of the HOF as compared with a series of substances ranging from other metal ions, metabolites, amino acids to proteins. Such superior fluorescence quenching effect endows the Cu 2+ quantification by this new HOF sensor with a wide linearity of 50–20 000 n m , a low detection limit of 10 n m , and good recoveries (89.5%–115%) in human serum matrices, outperforming most of the reported approaches. This work highlights the practicability of hydrogen‐bonded supramolecular engineering for designing facile and ultrasensitive biosensors for clinical free Cu 2+ determination.