Side‐Chain Engineering of Polythiophene Probes for Multimodal Discrimination of PFAS via Conformational Switching

Discriminating between perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), while suppressing interference from common surfactants, such as sodium dodecyl sulfate (SDS), remains a persistent challenge. In this work, we tackled this challenge through a rational side-chain engineering strategy, designing a series of cationic polythiophenes that exploit analyte-specific conformational transitions for unprecedented selectivity. Among them, PT32 was utilized as a trimodal (UV-vis absorption, colorimetric, and fluorometric) probe, enabling discriminative detection of PFOA/PFOS and distinction from other anionic surfactants. The system demonstrates clear visual and spectral discriminability, with PFOA inducing a distinct pink color, PFOS producing an orange-red response, and SDS showing negligible color change. This selectivity stems from variable conformational changes in the PT32 backbone (e.g., random aggregation, extended conformation, and supramolecular aggregation), which are driven by synergistic electrostatic, fluorophilic, and hydrophobic interactions. The PT32 probe exhibited remarkably LOD of 41.61 nM for PFOA and 25.71 nM for PFOS in fluorescence-based detection and achieved excellent recovery rates in real sample tests. Interestingly, the probe could be recycled post-detection and use multiple times. Hence, the side-chain engineering strategy not only addresses long-standing challenges in discrimination but also establishes a versatile design principle for developing advanced molecular probes.