Synthetic Ion Channels DOI: 10.1002/ange.201003849 Solid-State Ion Channels for Potentiometric Sensing** Gyula Jµgerszki, goston Takµcs, Istvµn Bitter, and Róbert E. Gyurcsµnyi* Biological ion channels (ICs) are protein pores with amino acid sequences providing functionalities rigorously spaced in the pore lumen to induce selective recognition and passage of ions through the cell membrane. [1] For example, the K + ion is at least 10 4 times more permeant through K + channels than the Na + ion. [2] Protein engineering and chemical modifica- tions offer the possibility to further enhance and diversify the molecular recognition properties of biological nanopores, [3] in particular their ion selectivity. [4] Apart from their biological significance and emerging sensing applications, [5] selective ion channels may certainly have a use in ion separation, for example in desalination [6] and cleanup of radioactive ions. [7] However, industrial-scale applications are limited, among other things, by the intrinsic fragility of the lipid bilayers and membrane proteins. Theoretical modeling studies suggest that by analogy to the selectivity filter of biological ICs, synthetic solid-state ion channels (nanotubes, nanopores) may also be constructed if their lumen is controllably modified with proper functionalities. [8] However, despite the successful use of nanopores modified with selective receptors for enantioselective [9] and DNA transport, [10] the selectivity of ion transport through nanopores has generally been based only on charge repulsion, [11, 12] size exclusion, [13] or polarity. [14] But these nanopores discriminate between groups of com- pounds having widely different physicochemical properties rather than providing selectivity for given species. Herein, we introduce for the first time solid-state ICs based on ionophore-modified nanopore arrays and, as a first application, their use for potentiometric sensing of a small inorganic ion. We used gold nanopores formed by electroless deposition of gold onto the surface of polycarbonate track- etch membranes with randomly distributed straight cylindri- cal pores (6  10 8 pores cm 2 with nominal diameters between 15 and 80 nm). [11] This arrangement allows for the sponta- neous self-assembly of thiol- and disulfide-bearing iono- phores and other selectivity-tuning compounds in a mono- molecular layer within the nanopores. Moreover, the gold plating restricts the effective diameter of the nanopores in order to have their chemically modified inner surfaces govern the transport. The proposed solid-state construction over- comes the fragility of biological ICs, while it also has the potential to relieve major limitations of conventional ion- ophore-based liquid-membrane ion-selective electrodes (ISEs), which constitute the foundation of the blood electro- lyte analyzer industry. [15] Such electrodes usually comprise membranes made of highly plasticized PVC [16] incorporating the ionophore, ion-exchanger, and other lipophilic additives. Any of the membrane components can leach into the sample solution, which limits the lifetime of the electrodes [17] and restricts their applicability. While efforts have been made to overcome these limitations by using self-plasticizing poly- acrylate-based membranes, [18] as well as by covalently con- fining active ingredients to the polymer matrix [19] or nano- particles, [20] there is still no complete solution to this problem. Moreover, not only leaching of ion-selective membrane (ISM) components into the sample is detrimental; owing to their selectivity-altering effects, the extraction of lipophilic sample components such as neutral lipids from human body fluids into the polymer membrane is also of concern. [21] This extraction of lipophilic components can be avoided only by using superhydrophobic fluorous-polymer-based ISMs, [22] which, owing to their extremely poor solvation capacity, resist the extraction of highly lipophilic components. How- ever, on the downside, the poor solvation makes such ISMs incompatible with commercially available ionophores and impedes their general applicability. Herein, we propose a solid-state ISM configuration with all components immobilized by Au  S bonds onto the walls of Au nanopores. This approach is radically different from recent efforts in nanoscaling potentiometric sensors, which only focus on a reduction in size of conventional membrane materials. [23] For proof of principle, a synthetic Ag + -selective thiacalixarene derivative bearing dithiolane moieties (SS-Ag- II, Scheme 1) was used to induce Ag + selectivity. [20] The length of the Au nanopores (6 mm) is approximately three orders of magnitude larger than the length of biological pores, and it approaches the thickness of conventional polymeric ISMs (ca. 100 mm). The theory of ionophore- based ion-selective membranes predicts that membranes of finite thickness, as in our case, require negative sites to induce a proper potentiometric response. [24] Consequently, cation- exchanger sites were generated using mercaptodecanesulfo- nate (MDSA), while, to take advantage of the latest results showing the superiority of fluorous ISMs, [22] a perfluorinated thiol derivative (PFT) was used to confer hydrophobicity to the Au nanopores (Scheme 1). [*] G. Jµgerszki, . Takµcs, Prof. R. E. Gyurcsµnyi Research Group for Technical Analytical Chemistry of the Hungarian Academy of Sciences, Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, GellØrt tØr 4, Budapest, 1111 (Hungary) Fax: (+ 36) 1-463-3408 E-mail: robertgy@mail.bme.hu Homepage: http://aak.bme.hu/Gyurcsanyi Prof. I. Bitter Department of Organic Chemistry and Technology Budapest University of Technology and Economics Budafoki fflt 8, 1111 Budapest (Hungary) [**] This work has been supported by the Hungarian Scientific Fund (OTKA NF 69262), T67585, and TMOP-4.2.1/B-09/1/KMR-2010- 0002. We thank Dr. D. Wegmann for careful reading of the manuscript. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201003849. Zuschriften 1694  2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. 2011, 123, 1694 –1697