Construction of Versatile Cascade Detection Platforms for Biomolecules Based on a Fluorescent Yttrium Metal–Organic Framework

Fluorescent metal–organic frameworks (MOFs) are recognized as powerful materials in chemical sensing due to their tunable structures and outstanding optical properties. However, the simplistic one-step detection mode of conventional fluorescent MOF probes severely restricts the analyte diversity, while their advancement in cascade detection systems is limited to a small set of classical MOFs without offering generalizable design logic. In this study, we report a novel fluorescent Y-based MOF, QUST-1, constructed via a linker desymmetrization strategy with the trapezoidal tetracarboxylate linker and Y–O chain node. QUST-1 selectively detects Fe 3+ through a fluorescence turn-off response without interference from Fe 2+ . To leverage this selectivity, we constructed a two-step “off–on” cascade sensing platform for ascorbic acid (AA), where AA reduces Fe 3+ to Fe 2+, restoring QUST-1 emission. Furthermore, coupling the system with α-glucosidase (α-Glu)-mediated enzymatic hydrolysis of 2-O-α- d -glucopyranosyl- l -ascorbic acid, which releases AA, enabled a three-step cascade process for the detection of α-Glu, a key enzyme involved in blood glucose regulation and a biomarker for type II diabetes, with a high sensitivity. This platform also facilitates the screening of α-Glu inhibitors, such as voglibose, which is relevant to antidiabetic and antiviral applications. By integrating the high specificity of the enzymatic reaction with the fluorescence of QUST-1, this work demonstrates the potential of MOF-based cascade systems for sequential detection of multiple analytes within a single assay.