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

The selective quantification of copper ions (Cu²⁺) in biosamples holds great importance for disease diagnosis, treatment, and prognosis since the Cu²⁺ 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 Cu²⁺ 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 Cu²⁺. 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 Cu²⁺ 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 Cu²⁺ quantification by this new HOF sensor with a wide linearity of 50-20 000 nm, a low detection limit of 10 nm, 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 Cu²⁺ determination.