Supramolecular strategy for probing conducting polymers at single molecule level.

Conducting polymers, such as poly(3,4-ethylenedioxythiophene) (PEDOT), represent a cornerstone of organic electronics, yet their investigation at the single-molecule level remains largely unexplored in nanopore systems. In particular, the poor aqueous solubility of PEDOT has so far limited its integration with biological interfaces. Here, we overcome this limitation by exploiting stable aqueous supramolecular dispersions formed by PEDOT complexed with cyclodextrins (CDs) (PEDOT·βCD and PEDOT·γCD). We investigate their interactions with two β-barrel biological nanopores Aerolysin (Ael) and Alpha-hemolysin (α-HL), using a combination of molecular docking simulations and nanopore resistive pulse sensing (Np-RPS). Our results reveal that individual PEDOT·CDs supramolecular assemblies exhibit strong and specific interactions with both nanopores, constituting, to the best of our knowledge, the first report of conducting polymer systems probed at the single-molecule level using biological nanopores. Surprisingly, the normalized current blockages remain comparable between cyclodextrin alone and PEDOT·CDs complexes. This observation is consistent with 1H-NMR evidence indicating encapsulation of PEDOT within the CDs cavity, yet suggests a negligible contribution of PEDOT to the ionic current modulation. We propose that this counterintuitive behavior arises from the intrinsic structure of PEDOT confined within the CD host, which preserves ion mobility through the nanopore despite cavity occupation by EDOT units. These findings highlight an unexpected decoupling between molecular occupancy and ionic transport, opening new perspectives for the study of conducting polymers in confined geometries which is a foundational step toward the development of hybrid ionic-electronic nanopore biosensing platforms.