Biological Cascade Catalysts Based on Structurally Regulated Covalent Organic Framework for Intuitive Glucose Colorimetric Sensing

The integration of chemical catalysts and biocatalysts into catalytic cascade reactions has garnered significant attention in recent years. However, its practical application has been limited due to several challenges, including the fragility of enzymes, inadequate carrier loading capacity, and poor catalytic efficiency. In this study, two types of Fe-ion-coordinated covalent organic frameworks (Fe-COFs) were synthesized in one pot by facilely changing the COF monomers. They have similar topologies but different electronic structures on the catalytic sites. These Fe-COFs demonstrated excellent peroxidase activity without interference of the oxidase activity, making them suitable for the immobilization of glucose oxidase (GOx). It is proved that both Fe-COFs could achieve a high GOx loading capacity of over 0.9 mg/mg_COF. The general applicability of Fe-COFs as carriers for GOx immobilization in the construction of cascade catalytic systems was confirmed. Among them, Fe-COF1 constructed by 2,2'-bipyridine-5,5'-diformaldehyde (Bpy) and 1,3,6,8-tetrakis(<i>p</i>-aminophenyl)-pyrene (Tpy) was optimized as the more suitable carrier toward the GOx immobilization for the quantitative colorimetric determination of trace glucose. Building upon this, a nanoenzyme-based colorimetric sensor that is compatible with smartphone biological systems was developed, facilitating efficient and convenient glucose quantification. The sensor demonstrated a strong linear relationship within the glucose concentration range of 10-1000 μM, with a limit of detection (LoD) of 1.4 μM. Additionally, it retained 90% of its catalytic activity after 10 repeated tests, proving its efficacy in sensitively detecting glucose in serum samples. This work expands the practical applications of biocascade catalysts based on COFs in colorimetric sensing and medical diagnostics.