Coptisine Chloride: A Natural Isoquinoline Alkaloid as a Dual-Responsive Aggregation-Induced Emission Sensor for Heparin and Protamine

Heparin (Hep) and its clinical antidote protamine (PRO) play essential yet antagonistic roles in anticoagulant therapy, necessitating reliable analytical tools to monitor their levels and interactions. Herein, we report that coptisine chloride (COP), a natural isoquinoline alkaloid, acts as an aggregation-induced emission (AIE) sensor enabling dual-responsive fluorescence modulation toward Hep and PRO. Owing to its rigid polycyclic and intrinsically twisted molecular framework, COP displays typical AIE behavior. In a DMSO/PBS mixture (PBS fraction = 99%, v/v), COP forms strongly emissive aggregates with Hep through electrostatically driven complexation, allowing sensitive Hep detection with a limit of detection (LOD) of 0.70 μg/mL. Subsequent competitive binding of PRO to Hep disrupts the COP–Hep aggregates, giving rise to fluorescence quenching and reversible PRO sensing (LOD: 0.49 μg/mL). Theoretical calculations together with multiple characterization techniques reveal an aggregation–disaggregation mechanism governing the dual fluorescence modulation. Moreover, COP achieves accurate Hep quantification in spiked diluted human serum, affording satisfactory linearity and recoveries (LOD = 0.71 μg/mL; recoveries 98.3–101.6%). These results demonstrate that COP, a structurally simple natural AIE luminogen, serves as a sustainable, biocompatible, and accessible tool for reversible Hep and PRO analysis in complex media.