Self-Assembled Dimers DOI: 10.1002/anie.200703971 Water and Hydrogen Halides Serve the Same Structural Role in a Series of 2+2 Hydrogen-Bonded Dimers Based on 2,6-Bis(2-anilinoethynyl)pyridine Sulfonamide Receptors** Orion B. Berryman, Charles A. Johnson II, Lev N. Zakharov, Michael M. Haley,* and Darren W. Johnson* The complex hydrogen-bonding interactions of the water molecule are remarkable: water plays a vital role in a number of systems ranging from the formation of hydrogen-bonded water oligomers [1] to the increased conformational stability of proteins [2] and the crucial synergistic hydrogen bonds formed in enzymatic [3] or biomimetic [4] active sites. In many cases these hydrogen bonds dictate both structure and function. In supramolecular chemistry, synergistic hydrogen bonding between water and organic molecules has helped to stabilize vase-like conformations of hosts for organic molecules [5] and to induce the formation of intricate hexameric nanoscale capsules stitched together with the aid of eight water molecules. [6] In both cases these hosts can be stabilized in wet organic or purely aqueous solvents. [7] Anions, on the other hand, tend not to share the structural hydrogen-bonding diversity of water, in part as a result of the weak basicity of anions and often because of a lack of directionality in their hydrogen-bond formation. [8,9] Nevertheless, there is an emerging use of anions as directing elements in self-assembly reactions. Notable examples include a double-stranded helix wrapped around two sulfate anions; [10] catenanes and other structures templated by the formation of hydrogen bonds to anions; [11] and supramolecular dimers, oligomers, and poly- mers linked together by anions. [12] Herein we report new receptors based on a 2,6-bis(2-anilinoethynyl)pyridine scaf- fold that surprisingly form 2+2 dimers with either water, halides, or both, depending on the protonation state of the receptor. To our knowledge, this is the first example of both halides and water molecules serving the same structural hydrogen-bonding role in a synthetic self-assembled system. [13] Our initial venture into the use of aryl ethynyl scaffolds as receptor molecules focused on sulfonamide-bearing 2,6-bis(2- anilinoethynyl)pyridine derivatives 1 and 2 (Scheme 1, py = pyridine), designed to target hydrogen-bonding guest mole- cules (see the Supporting Information). [14] CAChe semiem- pirical minimized molecular models suggested that selectivity for different guest molecules could be tailored by protonating the pyridine nitrogen atom, thus altering the cavity size, or by exchanging the binding substituents. The aryl ethynyl core 3 is prepared from 2-iodo-4-tert-butylaniline [15] in three steps in 60% overall yield. Conversion to sulfonamides 1 and 2 was accomplished in excellent yield by treatment of 3 with the corresponding sulfonyl chlorides (Scheme 1). Receptor molecules 1 and 2 have been characterized by 1 H and 13 C NMR, UV/Vis, fluorescence, and IR spectroscopy; melting point; and single crystal X-ray diffraction (see the Supporting Information). Interestingly, the 1 H NMR spec- troscopy signals of receptors 1 and 2 exhibit considerable concentration dependence in organic solvents. Furthermore, the sharp singlet typically observed at approximately d = 1.5 ppm for residual water in CDCl 3 appears as a broad downfield singlet (observed as far downfield as 4 ppm, depending on concentration), hinting at the hydrogen-bond- Scheme 1. [*] O.B.Berryman,Dr.C.A.JohnsonII,Dr.L.N.Zakharov, Prof.Dr.M.M.Haley,Prof.Dr.D.W.Johnson Department of Chemistry and Materials Science Institute University of Oregon Eugene, Oregon 97403-1253 (USA) Fax:(+ 1)541-346-0487 E-mail:haley@uoregon.edu dwj@uoregon.edu [**] This work was funded by the National Science Foundation (NSF) and the University of Oregon (UO). O.B.B. acknowledges the NSF for an Integrative Graduate Education and Research Traineeship (DGE-0549503). C.A.J. thanks UO for a Doctoral Research Fellow- ship. D.W.J. is a Cottrell Scholar of Research Corporation and gratefully acknowledges the NSFfor a CAREER award. We thank Prof. Julius Rebek,Jr. for helpful discussions. Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. Angewandte Chemie 117 Angew. Chem. Int. Ed. 2008, 47, 117 –120 # 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim