Molecule-within-molecule complexes provide physical organic chemistry with the means to study intermolecular forces, 1,2 to stabilize reactive intermediates, 3,4 and to probe the characteristics of the liquid state. 5 A new form of stereoisomerism, carceroisomerism, due to restricted tumbling of a guest bound within an asymmetric host 6 was also discovered. Larger container molecules are now available and feature cavities that can accommodate more than one guest. 7,8 These function as reaction chambers for some bimolecular processes 9 and can even form complexes-withincomplexes. 10 One of these systems revealed an unusual form of isomerism due to spatial relationships between the encapsulated species, and we describe it here.The system involves molecular capsule 1•1 8 (Figure 1), which is formed by the dimerization of tetraimide 1 in apolar organic solvents. The capsule is held together by hydrogen bonds and forms reversibly on time scales that range from hours to milliseconds. Because the capsule is cylindrical rather than spherical, guests experience and occupy various micro-environments along the cylinder's axis. The center, which is composed of eight imides, attractsswhen possiblesthe more polar parts of (1) Cram, D. J.; Cram, J. M. Container Molecules and their Guests; Royal Figure 2. Upfield portion of the 1 H NMR spectrum (600 MHz) of homoand heterocapsules, filled with picolines and toluene. In each experiment, equal amounts of the guests (ca. 30 equiv each) were added to a 0.5 mM solution of 1•1 in mesitylene-d12, at 295 ( 1 K. (a) R-and -picolines, (b) R-and γ-picolines, (c) -and γ-picolines, (d) R-, -and γ-picolines, (e) γ-picoline and toluene.Figure 1. Two molecules of tetraimide (left) self-assemble through eight bifurcated hydrogen bonds into the cylindrical capsule 1•1 (center), which is represented by the cartoon (right).4928

The synthesis of new resorcinarene derivatives featuring extended sides and self-complementary hydrogen-bonding sites is described. Dimerization occurs in solvents such as toluene-d 8, and large cavities result. The dimerization constant K D = 1700 ± 250 M-1 was determined, and the cavity of the dimer was found to encapsulate two heptyl or octyl chains of the subunits. It is proposed that hydrogen bonding and self-inclusion are responsible for the large and compensating thermodynamic parameters for dimerization:  ΔH = −20.9 ± 1.3 kcal mol-1 and ΔS = −58 ± 5 cal mol-1 K-1.

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Cavitands with self-complementary shapes (3 and 4) were prepared by the covalent attachment of adamantane guest molecules to the upper rim of the host structures. Relatives of the "self-folding" cavitands 2, these new structures possess a seam of intramolecular hydrogen bonds that stabilize the folded conformation. Their self-complementary shapes result in the formation of noncovalent dimers of considerable kinetic and thermodynamic stability (-∆G 295 ) 4.5 kcal/mol for 3a and 6.5 kcal/mol for 4a in p-xylene-d 10 ). The dimerization of cavitands 3 and 4 is reversible and subject to control by solvent and temperature. The dimerization process is enthalpically favored and entropy opposed and occurs with significant enthalpy-entropy compensation.

New types of resorcinarene-based nanoscale container molecules 2 and 3 are described. They feature reversibly folding unimolecular cavities of nanoscale dimensions and ∼800 Å 3 internal volume; they are among the largest synthetic unimolecular hosts prepared to date. Two seams of intramolecular hydrogen bonds, provided by 12 secondary amides, control the guest uptake and release. The hydrogen bonds resist the unfolding of the host and increase the energetic barrier to guest exchange. Exchange is slow on the NMR time scale (room temperature), and kinetically stable complexes result. The direct observation of bound species and the stoichiometry of the complexes are reported. A series of adamantyl and cyclohexyl guests 11-19 of various shapes and lengths were prepared and used to estimate the hosts' capacities. Compound 2 exists in an S-shaped conformation and its two cavities act independently; each half of host 2 formed kinetically stable complexes with either two identical or different guest molecules. The C-shaped host 3 accommodates rigid and long guests with association constants (K a ) between 500 ( 50 M -1 (-∆G 295 ) 3.6 ( 0.1 kcal mol -1 ) and 270 ( 100 M -1 (-∆G 295 ) 3.2 ( 0.2 kcal mol -1 ) for adamantyl derivatives. With the more flexible and/or shorter guests, fast exchange between the free and complexed guest species was observed at room and higher temperatures (in toluene-d 8 ). Guest exchange rates of the new hosts are considerably faster than rates seen with typical hemicarceplexes but slower than those of other open-ended cavitands.