Two-dimensional covalent organic framework-based hybrid nanosheets for electrochemical detection of 5-fluorouracil and uracil in biofluids†

Owing to the unique properties of high porosity, outstanding chemical stability, and designable structures, vast applications of covalent organic frameworks (COFs) have been explored in a wide range of areas including energy storage, catalysis, gas separation, etc. Nevertheless, from the perspective of electrochemical sensing, the conductivity of COFs is not satisfactory. Here, a two-dimensional (2D) hybrid nanosheet combining a COF, a supramolecular host, and nanomaterials was constructed by assembling cucurbit[8]uril (CB8) onto the surface of the COF, and achieved in situ growth of uniformly dispersed AuNPs with the aid of the modulation effect of CB8 to synergistically enhance the sensing performance. By taking advantage of the abundant active loading sites and large specific area of the 2D-COF, excellent conductivity of AuNPs, and host–guest binding ability of CB8, the prepared COF/CB8/AuNPs is utilized to modify the glassy carbon electrode (GCE) as an advanced electrochemical sensor for simultaneous detection of structurally similar analytes, e.g. antineoplastic agent 5-fluorouracil (5-FU) and RNA base uracil (U) using differential pulse voltammetry, achieving detection limits down to the nanomolar level (e.g. 0.037 and 0.074 μM for 5-FU and U, respectively) and the physiologically relevant linear detection range within the sub-micromolar window. Impressively, the prepared COF/CB8/AuNPs/GCE sensor is considerably robust in complicated biofluids, allowing for detecting 5-FU and U in unprocessed native synthetic urine (SU) and whole fetal bovine serum (FBS), which remained highly challenging for electrochemical sensors. This study elucidates the integration of COFs with supramolecular host systems, paving the way for the development of advanced electrochemical sensors for rapid and onsite detection in pharmaceutical diagnostic applications.