ZUSCHRIFTEN Angew. Chem. 2001, 113, Nr. 12  WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001 0044-8249/01/11312-2325 $ 17.50+.50/0 2325 Cesium- and Rubidium-Selective Redox-Active Bis(calix[4]diquinone) Ionophores** Philip R. A. Webber, George Z. Chen, Michael G. B. Drew, and Paul D. Beer* The synthesis of redox-active molecular receptors designed to selectively recognize and electrochemically sense charged or neutral guest species of biological and environmental importance is an area of intense current interest. [1] A number of research groups have incorporated redox-active transition metal and organic centers into a variety of macrocyclic structural frameworks based on crown ethers, cryptands, and calixarenes, and shown some of these systems to be selective and electrochemically responsive to the binding of metal cations, particularly lithium, [2] sodium, [3] and potassium. [4] However, the construction of redox-active ionophores for the selective recognition of the larger cesium and rubidium metal cations has not, to our knowledge, been reported. This situation is surprising in view of the environmental concern for monitoring radioactive cesium in nuclear waste solutions [5] and the potential use of rubidium isotopes in radiopharma- ceutical reagents. [6] We report here the synthesis, coordina- tion, and electrochemical investigations of novel bis(calix[4]- diquinone) receptors L 1 and L 2 , and demonstrate their remarkable ability to selectively complex and electrochemi- cally sense cesium and rubidium cations. Reaction of a solution of p-tert-butylcalix[4]arene (1) in acetonitrile with propane-1,3-ditosylate, 1,4-dibromobutane, or 1,5-dibromopentane in the presence of potassium carbo- nate gave the bis(calix[4]arene) derivatives 2, 3, and 4 in 30, 23, and 26 % yields, respectively (Scheme 1). Oxidation of these compounds with Tl(OCOCF 3 ) 3 in trifluoroacetic acid [4a, 7] gave the new bis(calix[4]diquinone) ionophores L 1 , L 2 , and L 3 in respective yields of 28, 10, and 9 % after column chromatography and recrystallization. [8] Electrospray mass spectrometry (ES-MS) competition ex- periments gave the first qualitative indication that L 1 and L 2 displayed notable selectivity preferences for Cs  and Rb  ions. The electrospray mass spectra of equimolar Group 1 metal iodides in the presence of solutions of the tetraquinone ligands in DMSO revealed the most intense peaks occurred at [6] T. deLumley-Woodyear, C. N. Campbell, A. Heller, J. Am. Chem. Soc. 1996, 118, 5504 ± 5505. [7] K. M. Millan, A. Saraullo, S. R. Mikkelsen, Anal. Chem. 1994, 66, 2943 ± 2948. [8] S. Takenaka, K. Yamashita, M. Takagi, Y. Oto, H. Kondo, Anal. Chem. 2000, 72, 1334 ± 1341. [9] A. Bardea, F. Patolsky, A. Dagan, I. Willner, Chem. Commun. 1999, 21 ± 22. [10] A. Bardea, A. Dagan, I. Ben-Dov, B. Amit, I. Willner, Chem. Commun. 1998, 839 ± 840. [11] J. Wang,M. Jiang, T. W. Nielsen, R. C. Getts, J. Am. Chem. Soc. 1998, 120, 8281 ± 8282. [12] F. Patolsky, E. Katz, A. Bardea, I. Willner, Langmuir 1999, 15, 3703 ± 3706. [13] F. Patolsky, A. Lichtenstein, I. Willner, J. Am. Chem. Soc. 2000, 122, 418 ± 419. [14] F. Patolsky, A. Lichtenstein, I. Willner, Angew. Chem. 2000, 112, 970 ± 973; Angew. Chem. Int. Ed. 2000, 39, 940 ± 943. [15] F. Patolsky, K. T. Ranjit, A. Lichtenstein, I. Willner, Chem. Commun. 2000, 1025 ± 1026. [16] All primers were provided by Sigma-Genosys, UK. The primers were provided as disulfides, and the thiolated oligonucleotides were prepared by reacting the commercial disulfides with 0.04 m threo- 1,4-dimercapto-2,3-butandiol (DTT) for 16 h at room temperature followed by the purification of the reduced DNA on a NAP-10 column (Pharmacia). [17] Quartz crystals, 9MHz AT-cut sandwiched between two Au-electro- des (area 0.196 cm 2 , roughness factor ca. 3.5) were used in the studies. [18] The M13 mp8 () strand, nucleotides, biotinylated-dCTP and Klenow fragment were all provided by Sigma. Polymerization was performed in a 10 mm Tris buffer solution, pH 7.5, that contained 50 mm of KCl, 5mm MgCl 2 , and 20 U mL 1 of the enzyme, dGTP, dATP, dTTP, dCTP, and biotinylated-dCTP (1:1:1:2/3:1/3, each base 1 mm). [19] The avidin ± alkaline phosphatase conjugate was coupled to the biotinylated surface by treating the electrodes or the quartz crystal with avidin ± alkaline phosphatase conjugate (10 nmol mL 1 ) in 0.1 m Tris buffer for 20 min. The resulting electrodes were treated with 2  10 3 m 5-bromo-4-chloro-3-indolyl phosphate (Aldrich) in a Tris buffer for 20 min. [20] A. B. Steele, T. M. Hernland, M. Tarlov, Anal. Chem. 1998, 70, 4670 ± 4677. [21] A. J. Bard, L. R. Faulkner, Electrochemical Methods: Fundamentals and Applications, Wiley, New York, 1980. [22] L. Blanco, A. Bernard, J.M. Lazaro, G. Martin, C. Garmendia, M. Salas, J. Biol. Chem. 1989, 264, 8935 ± 8940. [23] HeLa cell cultures were inoculated with vesicular stomatitis virus-NJ. The culture medium was collected after 24 h, and clarified by centrifugation at 4 8C at 3000 g for 20 min. The supernatant solution was overlaid upon a 20 % sucrose cushion in TNE buffer (TNE: 10 mm Tris buffer, pH7.8, 100 mm NaCl, 1 mm EDTA; EDTA  ethylendiaminetetraacetate) and subject to centrifugation for 60 min at 27000 rpm with a SW 27 Beckmann ultracentrifuge. The pellet was dissolved in a mixture of 1:1 of phenol and TNE buffer that included 0.1% sodium dodecyl sulfate (SDS). Following extraction, the RNA was precipitated in ethanol that was incubated at  70 8C for 20 min and then subject to centrifugation for 20 min at 10 000 rpm at 4 8C. The RNA was dissolved in TNE buffer. [24] Enhanced avian reverse transcriptase product of Sigma. [25] Yeast RNA of heterogeneous length of 2 ± 7 kb (Boehringer Mann- heim). [*] Prof. P. D. Beer, P. R. A. Webber Department of Chemistry Inorganic Chemistry Laboratory, University of Oxford South Parks Road, Oxford OX1 3QR (UK) Fax ( 44) 1865-272690 E-mail : paul.beer@chem.ox.ac.uk Dr. G. Z. Chen Department of Materials Science and Metallurgy University of Cambridge Pembroke Street, Cambridge CB2 3QZ (UK) Prof. M. G. B. Drew Department of Chemistry University of Reading Whiteknights, Reading RG6 2AD (UK) [**] We thank the EPSRC for a studentship and the EPSRC and University of Reading for funds for the crystallographic image plate system. Supporting information for this article is available on the WWW under http://www.angewandte.com or from the author.