Fabrication of Metal-Free Covalent Organic Frameworks (COF)-Based Nanozyme ETTATFB-COOH via the Doebner Reaction for Dual-Channel Sensing of Aristolochic Acid A

Abstract Covalent organic frameworks (COF) have attracted considerable attention in the fields of sensing and catalysis owing to their unique structural and physicochemical properties. However, their practical applications remain limited by insufficient stability and the lack of integrated multifunctionality. In this work, ETTATFB was initially synthesized using 4,4′,4″,4‴-(ethene-1,1,2,2-tetrayl)tetraaniline (ETTA) and 1,3,5-triformylbenzene (TFB) as the building blocks. The imine linkages in ETTATFB were then converted into quinoline rings via Doebner reaction, with carboxyl groups being introduced simultaneously, to yield ETTATFB-COOH. This conversion of the reversible bonds significantly improved the solvent stability and π-electron delocalization of the framework, thereby enhancing its potential for practical applications. For sensing applications, ETTATFB-COOH not only retained its strong fluorescence emission, enabling fluorescent detection of aristolochic acid A (AA), a Group 1 carcinogen, with a low limit of detection of 0.0453 μM, but also exhibited enhanced oxidase-like activity, which enabled the colorimetric sensing of AA. Additionally, BPNN models were developed by integrating the responses obtained from the fluorescent and colorimetric sensing modes to enable accurate quantification of AA concentrations. In summary, this work presents a simple yet effective strategy for simultaneously improving the stability and functional performance of COF, while demonstrating the potential of metal-free COF-based nanozymes for multimodal sensing applications.