An achiral form of the hexameric resorcin[4]arene capsule sustained by hydrogen bonding with alcohols { Onome Ugono and K. Travis Holman* Received (in Austin, TX, USA) 20th March 2006, Accepted 9th April 2006 First published as an Advance Article on the web 26th April 2006 DOI: 10.1039/b604148e The well-known hexameric capsules sustained by self-assembly of resorcin[4]arenes 1 with water molecules (1 6 ?(H 2 O) 8 ) are shown to assemble similarly with (¡)-2-ethylhexanol (2EH) as an achiral 1 6 ?(2EH) 6 ?(H 2 O) 2 species which further encapsulates 2EH. The discovery in 1997 by Atwood and MacGillivray of large, chiral, hexameric assemblies of calix-resorcin[4]arenes, namely 1 6 ?(H 2 O) 8 (Scheme 1), 1 and the subsequent report of a related hexamer, 2 6 , 2 were of particular significance to the fields of self- assembly and molecular encapsulation. 3 Whereas the building blocks of some designer molecular capsules may require multi-step syntheses and yield cavities that encapsulate a few small molecules, the discovery of 1 6 ?(H 2 O) 8 and 2 6 demonstrated that particularly large cavities (1.3–1.5 nm 3 ) can be achieved from simple, commercially available starting materials. Indeed, 1 6 ?(H 2 O) 8 and 2 6 assemble nearly quantitatively in solution 4 and 2 6 has even been synthesized in a single step by solvent-free means. 5 Perhaps more significant, however, is the notion that these species may guide design strategies toward increasingly sophisticated many-compo- nent supramolecular assemblies. 6 Extensive study of these assemblies and other related large molecular containers has therefore been of broad interest. 3,7 We report herein the discovery that hexameric assemblies related to 1 6 ?(H 2 O) 8 are possible wherein alcohols, namely (¡)-2-ethylhexanol (2EH), replace water molecules on the surface of the assembly. The ‘‘hexamer’’ of 1 6 ?(H 2 O) 8 is actually a fourteen-component particle that may further encapsulate several small molecule guests. 1,4 The assembly is sustained by an impressive array of sixty complementary H-bonds and the eight water molecules of 1 6 ?(H 2 O) 8 play an integral role by participating in twenty-four of the thirty-six intermolecular H-bonds. That alcohols might effectively replace the water molecules of the hexameric capsule 1 6 ?(H 2 O) 8 is not immediately obvious. In a supramolecular sense, alcohols are by no means isomorphous with water. Clearly, water, with its two hydrogens, is capable of functioning as a double H-bond donor whereas alcohols are single H-bond donors. Moreover, it has already been demonstrated that certain alcohols (e.g., isopropanol) promote the assembly of 1a into ‘‘dimeric’’ (actually, ten-component), carcerand-like capsules, 1a 2 ?(ROH) 8 , wherein each alcohol participates in two intermolecular H-bonds and functions simultaneously as a single donor and a single acceptor. 8 In 1 6 ?(H 2 O) 8 , however, each water molecule participates in three intermolecular H-bonds. The H-bonding pattern dictates that four of the eight water molecules must function as double donors and single acceptors and four must serve as single donors and double acceptors. Four water molecules therefore direct their ‘‘extra’’ O–H groups away from the surface of the capsule. So, it was conceivable to us that these four might be readily replaced by alcohols to give assemblies of the form 1 6 ?(ROH) 4 ?(H 2 O) 4 , exhibiting an H-bonding array identical to 1 6 ?(H 2 O) 8 , but decorated with selected, perhaps strategically functionalized, alcohols. In exploration of this theme, 1a 9 was crystallized from several alcoholic solvents. As expected, single crystal X-ray analysis reveals that some alcohols yield dimeric capsules of the form 1a 2 ?(ROH) 8 (e.g. ROH 5 2-ethylbutanol, (¡)-2-butanol) and others yield non-capsular structures. X-ray analysis of crystals of 1a grown by evaporation from 2EH, however, reveals a large, self- assembled capsule consisting of six molecules of 1a, six molecules of 2EH, and two adventitious water molecules. The capsule is thus formulated as 1a 6 ?(2EH) 6 ?(H 2 O) 2 , hereafter 3a (Fig. 1).{ Though the atomic positions of the guests encapsulated by 3a are highly disordered in the structure, SQUEEZE 10 analysis estimates the cavity volume and number of electrons corresponding to encapsulated species to be 1290 A ˚ 3 and 220 electrons, respectively. These data correspond well to three molecules of 2EH (calc. 222 electrons). Moreover, 1 H NMR, thermal gravimetric, and elemental analysis support the contention that 3a encapsulates three molecules of 2EH in the solid state.{ The crystals are thus formulated as 3a,3(2EH). Department of Chemistry, Georgetown University, Washington, DC, USA. E-mail: kth7@georgetown.edu; Fax: +1 202 687 6209; Tel: +1 202 687 4027 { Electronic supplementary information (ESI) available: experimental details, complete spectra. See DOI: 10.1039/b604148e Scheme 1 COMMUNICATION www.rsc.org/chemcomm | ChemComm 2144 | Chem. Commun., 2006, 2144–2146 This journal is ß The Royal Society of Chemistry 2006