TREN‐Amino‐1,8‐Naphthalimide Fluorescent Receptors for Selective Binding and Quantitative Sensing of Heparin Polyanion in Clinically Relevant Conditions

The selective detection and quantification of heparin is important in clinical settings, particularly for the improved management of anticoagulant therapy. Herein, we report two easy‐to‐use water‐soluble fluorescent receptors, TREN‐Nap‐1 and TREN‐Nap‐2 , based on the amino‐1,8‐naphthalimide fluorophore for the selective and reversible detection of heparin in clinically relevant conditions. The fluorescence titration studies revealed that both sensors exhibited a high affinity for heparin, with a low detection limit of 1.18 ng mL − 1 . The fluorescence emission intensity of the sensors is quenched upon binding with heparin due to the formation of aggregates through electrostatic interactions. Moreover, both sensors displayed high selectivity toward heparin over other glycosaminoglycans, such as hyaluronic acid and chondroitin sulfate, as well as other potent binding competitors, including serum albumins (BSA and HSA), glucose, citrate, and other relevant anions. Interestingly, the sensor–heparin complex can disaggregate in the presence of protamine (an antagonist), resulting in an “off−on” fluorescence response, indicating reversibility. Most importantly, the human serum assay shows a strong linear relationship within the heparin concentration range of 0–27 μg mL − 1 , suggesting potential clinical applicability for quantifying heparin in serum. These results demonstrate the high potential of TREN‐Nap‐1 and TREN‐Nap‐2 for detecting heparin polyanion under clinically relevant conditions.