DOI: 10.1002/chem.201101748 The Structure of Water in p-Sulfonatocalix[4]arene Katharina Fucke, [a] Kirsty M. Anderson, [a] Maria H. Filby, [a] Marc Henry, [b] Jonathan Wright, [c] Sax A. Mason, [d] Matthias J. Gutmann, [e] Leonard J. Barbour, [f] Clive Oliver, [g] Anthony W. Coleman, [h] Jerry L. Atwood, [i] Judith A. K. Howard, [a] and Jonathan W. Steed* [a] Dedicated to our friend AndrØs Goeta, who will be sorely missed Introduction There is significant current interest in abiotic or biomimetic “water cluster” structures, for example, the report in 1998 of the oxygen atom skeleton of a discrete (H 2 O) 10 cluster that closely resembles cubic ice, [1] one of the two most common forms of ice. [2] Since then there have been a number of papers that have reported the existence of a diversity of water clusters or chains derived from X-ray and, in a few cases, neutron data, [3] and the topic has been reviewed, [4] al- though it has been pointed out that the novelty of some of these structures must be interpreted with caution. [5] The ex- istence and structure of water in crystalline hydrates is of immense importance to the pharmaceuticals industry [6] and has been systematically classified in surveys of the Cam- bridge Structural Database (CSD). [7] There have been re- ports of the role of water clusters in templating inorganic nanoporous materials; the structure of water in confined en- vironments, particularly in “functional” water structures such as those found in vesicles and biological channels; [8] and its role in ion transport in nanocapsules. [9] In addition, various small water aggregates have been implicated in the anomalous behaviour of liquid water. [10] There is evidence from cluster analysis that water clusters stabilise biomole- cules such as alanine racemase and supply the active site with water, thereby allowing rapid equilibration of active- site protons with solvent. [11] Water clusters play a significant role in the structure of Scaphara dimeric haemoglobin, [12] crambin, [13] actinidin [14] and carbonic anhydrase C, [15] and the Abstract: Tetrasodium p-sulfonatoca- lix[4]arene exists as a hydrate with ap- proximately 14 water molecules and has three polymorphic modifications, all of which contain a water molecule in the molecular cavity that is engaged in OH···p interactions. Single-crystal neutron structures are reported for two of these three forms and reveal a “compressed” water molecule with short OH bonds. Partial atomic charges and hardness analysis (PACHA) calcu- lations based on the neutron coordi- nates give an OH···p interaction energy of 6.9–7.5 kJ mol 1 . The PACHA analy- sis also reveals the dominance of the charge-assisted hydrogen bonds from the Na + -coordinated water molecules. The instability of the crystal towards dehydration can be traced to an unco- ordinated lattice water site. The re- markable calixarene-Na + -hydrate motif is conserved almost unchanged across all three polymorphs. A single- crystal neutron structure is also report- ed for pentasodium p-sulfonatocalix[4]- arene·12 H 2 O, which exhibits an intra- cavity water molecule that is engaged in both OH···p and OH···O hydrogen bonding. The shorter covalent bond to the hydrogen atom that forms the in- teraction with the aromatic ring is again apparent. Keywords: aromaticity · calixar- enes · neutron diffraction · structure elucidation · water chemistry [a] Dr. K. Fucke, Dr. K. M. Anderson, Dr. M. H. Filby, Prof. J. A. K. Howard, Prof. J. W. Steed Department of Chemistry, Durham University South Road, Durham, DH1 3LE (UK) Fax: (+ 44) 191-384-4737 E-mail : jon.steed@durham.ac.uk [b] Prof. M. Henry Institut Le Bel, UniversitØ Louis Pasteur 4 Rue Blaise Pascal, 67070 Strasbourg Cedex (France) [c] Dr. J. Wright European Synchrotron Radiation Facility 6 Rue Horowitz, 38042 Grenoble Cedex (France) [d] Dr. S. A. Mason Institut Laue-Langevin, 6 Rue Horowitz 38042 Grenoble Cedex (France) [e] Dr. M. J. Gutmann STFC Rutherford Appleton Laboratory ISIS Neutron and Muon Source Didcot, OX11 0QX (UK) [f] Prof. L. J. Barbour Department of Chemistry University of Stellenbosch (South Africa) [g] Dr. C. Oliver Department of Chemistry, University of Cape Town Rondebosch 7701 (South Africa) [h] Prof. A. W. Coleman LMI, UniversitØ Lyon, 1, Bvd 11 Novembre Villeurbanne, 69622 (France) [i] Prof. J. L. Atwood Department of Chemistry, University of Missouri Columbia, MO 65211 (USA) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201101748. Chem. Eur. J. 2011, 17, 10259 – 10271 # 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 10259 FULL PAPER