Discriminating and selective detection of structurally similar multi-analytes remains a major challenge in chemical sensing due to severe cross-response interference from shared molecular skeletons and functional groups. To address this, we report a novel zeolite-based nanopore sensing strategy that leverages the uniform nanopore channels and tunable adsorption properties of zeolites for achieving high selectivity in multi-analyte systems. Using bisphenol AF (BPAF) and bisphenol S (BPS)—two electrochemically overlapping phenolic pollutants with extreme similar structure—as model targets, we engineered and studied four zeolites: hydrophilic Hβ, surface-hydrophobic OS-Hβ (prepared by organosilane modification of Hβ), and two hydrophilic Y-type zeolites with contrasting Si/Al ratios (HY‑686 and NaY‑5). Notably, these materials exhibited distinct nanopore adsorption preferences: Hβ selectively adsorbed BPS, whereas OS-Hβ favored BPAF only; HY‑686 adsorbed both bisphenols, while NaY‑5 showed negligible uptake. Mechanistic studies revealed that for Beta-type zeolites with similar nanopore sizes, surface hydrophilicity/hydrophobicity governs selectivity, whereas for hydrophilic Y-type zeolites, nanopore size plays the decisive role. Building on this principle, we developed an innovative electrochemical nanopore sensing platform that integrates selective molecular absorption, in situ electrocatalysis, and interference-free detection, enabling accurate discrimination and quantification of BPAF and BPS in complex samples. This work not only resolves a persistent sensing challenge for structurally analogous analytes but also establishes a generalizable molecular‑sieving nanopore sensing principle for selective adsorption, electrocatalysis, and sensing applications.
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