Design and Synthesis of D–A Structure Fluorescent Probes for Specific Detection of Human Serum Albumin Using Aggregation‐Induced Emission

Abstract Elevated levels of human serum albumin (HSA) serve as an early indicator of cardiovascular and renal diseases in diabetic and hypertensive patients. This study focuses on the design and synthesis of two fluorescent probes, Nap‐B1 and Nap‐KL, which were developed by functionalizing the “D–A” structural framework consisting of naphthalimide derivatives (A) and triphenylamine (D) with pyridine/quinoline cations. These sensors are intended for the quantitative detection of HSA in urine, specifically recognizing HSA and inducing fluorescence “turn‐on” upon binding. Both Nap‐B1 and Nap‐KL is demonstrated high selectivity for HSA, stability independent of environmental factors, and sensitivity for rapid detection. Changes in Zeta potential, dynamic light scattering (DLS), fluorescence lifetime, and fluorescence intensity were observed, which result from alterations in HSA conformation before and after sensor binding. Molecular docking experiments further confirmed that the probes bind to HSA via hydrophobic interactions and electrostatic adsorption, forming a probe‐HSA complex and triggering the fluorescent response.