Albumin‐Assisted Supramolecular Probe for Ratiometric Detection of PFAS in Aqueous Medium

Per‐ and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants, and their growing concern requires the development of efficient detection methodologies. The present article introduces a novel supramolecular host–guest sensing system using human serum albumin (HSA) as the host and a specifically designed chromophoric azo dye, (E)‐(2‐hydroxy‐5‐((3,4,5‐trimethoxyphenyl)diazenyl)phenyl)(pyrrolidine‐1‐yl)methanone (TPAZ), as the guest. The probe was used for ratiometric and colorimetric detection of PFOS, PFOA, and PFNA. Absorbance and fluorescence techniques were used to study the photophysical properties, binding stoichiometry, and site‐specific interactions. The density functional theory calculations also supporting strong intramolecular charge transfer behavior and visible‐light absorption. The TPAZ–HSA complex showed distinct spectral shifts and a visible color change from yellow to colorless upon interaction with PFAS, enabling rapid and selective detection, however, the sensor is selective toward PFAS as a class but not toward individual PFAS. This probe enables simple paper‐based test strips for on‐site PFAS detection in water using smartphhgone images. Molecular docking revealed the sensing mechanism and competitive binding of TPAZ and PFAS at albumin sites. This article demonstrates a simple, cost‐effective, and selective sensing approach for on‐site detection of PFAS in aqueous systems.