News and Publications

Intermolecular Forces and Interactions

J. Rebek, Jr., C. Boss, M. Brody, R. Castellano, T. Heinz, G. Hilmersson, A. Luetzen, S. Ma, T. Martin, S. Mecozzi, D. Mink, B. O'Leary, U. Obst, K. Pryor, D. Pupowicz, J. Rivera, D. Rudkevich, J. Santamaria, C. Schalley, T. Szabo, J. Toker, F. Tucci, B. Vauzeilles, S. Waldvogel, S. Wallbaum, A. Wartini, P. Wash

SELF-ASSEMBLY

We continue to be captivated by the rules that govern molecular self-assembly. Our current premise is that increasing the informational content in a monomeric subunit will result in an assembly of greater predictability and 3-dimensional structure. Some progress has been made on this front. For example, by knowing that heterodimerization occurs between different calixarene subunits, it is possible to predict the details of the assemblies illustrated in Figure 1. One assembly involves a central core molecule, 3 "guest" molecules, and 3 capping units. All form spontaneously from the individual subunits in solvents that are friendly to hydrogen bonding. The subunits assemble in a dynamic manner; they associate and dissipate on a timescale that ranges from minutes to milliseconds, long enough for many activities--even chemical reactions--to occur with the molecule held inside.

We have also studied the internal dynamics of molecule-within-molecule complexes. For example, when a large guest, [2.2]paracyclophane (Fig. 2), is encapsulated in the molecular "softball," the carbon 13 correlation times of the host and the guest correspond.
Accordingly, the cyclophane is not free to tumble within the softball but must rotate in the same direction as the components of the softball.

We have also explored the dynamics of guest exchange within these systems. We saw that rather than coming completely apart, guests exchange through the formation of large openings on the molecular surface. The openings allow exchange with molecules in solution in an orderly sequence: a substitution reaction on the supramolecular scale. Studying bimolecular reactions within these systems is also possible. We have shown that a range of Diels-Alder reactions are accelerated within the softball capsule. A vaselike structure for encapsulation of adamantanes is depicted in Figure 3.

MOLECULAR DIVERSITY AND COMBINATORIAL CHEMISTRY

Protein-protein and protein--nucleic acid interactions continue to define targets for the medicinal chemist. Nonetheless, the large surface areas usually involved make these targets difficult to study. One approach to overcome these difficulties involves using medium-sized, rather than small, molecules in which several functional groups protrude on the same surface.
The molecular platform shown in Figure 4 features 3 groups, all on the same side of the molecule. The subtle hydrogen-bonding characteristics of the framework ensure that a single conformation is favored; the molecule is quite rigid. We have prepared several versions of this platform and have developed some combinatorial libraries for use in biological screening.

PUBLICATIONS

Castellano, R.K., Rebek, J., Jr. Formation of discrete, functional assemblies and informational polymers through the hydrogen bonding preferences of calixarene aryl and sulfonyl tetraureas. J. Am. Chem. Soc. 120:3657, 1998.

Hilmersson, G., Rebek, J., Jr. Coupling of molecular motions through non-bonding interactions: ¹³C NMR spin-lattice relaxation studies of a host-guest complex. Magn. Reson. Chem., in press.

Ma, S., Rudkevich, D.M., Rebek, J., Jr. "Deep-cavity" resorcinarenes dimerize through hydrogen bonding and self-inclusion. J. Am. Chem. Soc. 120:4977, 1998.

O'Leary, B.M., Grotzfeld, R.M., Rebek, J., Jr. Ring inversion dynamics of encapsulated cyclohexane. J. Am. Chem. Soc. 119:11701, 1997.

Rebek, J., Jr. Reversible encapsulation and its consequences in solution. Accounts Chem. Res., in press.

Rivera, J.M., Martín, T., Rebek, J., Jr. Structural rules governing self-assembly emerge from new molecular capsules. J. Am. Chem. Soc. 120:819, 1997.

Rojas, C.M., Rebek, J., Jr. Convergent functional groups: Intramolecular acyl transfer through a 34-membered ring. J. Am. Chem. Soc. 120:5120, 1998.

Rudkevich, D.M., Hilmersson, G., Rebek, J., Jr. Intramolecular hydrogen bonding controls the exchange rates of guests in a cavitand. J. Am. Chem. Soc. 119:9911, 1997.

Tokunaga, Y., Rebek, J., Jr. Chiral capsules: 1. Softballs with asymmetric surfaces bind camphor derivatives. J. Am. Chem. Soc. 120:66, 1997.

Tokunaga, Y., Rudkevich, D.M., Rebek, J., Jr. Solvation and the synthesis of self-assembled capsules. Angew. Chem. 36:2656, 1997.