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TSRI Scientific Report 2003

The Inner Space of Molecules


J. Rebek, Jr., P. Ballester, S. Biros, W.-D. Cho, S. Conde Ceide, J. Friese, A. Gissot, S. Gu, F. Hof, A. Job, D. Johnson, Y. Kim, L. Kröck, L. Palmer, B. Purse, A. Scarso, A. Shivanyuk, L. Trembleau, E. Ullrich, M. Yamanaka

Self-assembled host capsules that can more or less surround simple target guests create molecules within molecules. We are concerned with the following questions: What is it like inside a molecule? Is there space for more than a single guest? How do guests get in and out? What are the relationships between 2 or more guest molecules inside? Does it matter if the guest is a gas or liquid? We use nuclear magnetic resonance methods for study of these systems in solution and, when appropriate, x-ray crystallography for the solid state. The results are giving a new picture of the different stable phases of matter.

Cylindrical capsules offer many advantages for our investigations. A cylindrical capsule has a sizable volume of more than 400 Å3 and the shape of the cavity shown in Figure 1. It also has an uncanny ability to select guests that fill the right amount of space in the host structure. For example, 3 molecules of chloroform or 3 molecules of isopropyl chloride will fill a cylindrical capsule. However, coencapsulation can also occur: as chloroform is added to a solution of a capsule containing isopropyl chloride, new capsular assemblies appear with successive replacement of one guest by another. These assemblies create new forms of isomerism that we termed isomeric constellations. Because the solvent molecules are too large to squeeze past each other while in the capsule, the lifetime of these isomers (about 1 second) is long enough to distinguish them by using nuclear magnetic resonance spectroscopy. The different constellations also represent a form of information. When the precise arrangements can be controlled, maintained for longer times, and retrieved readily, nanoscale data storage will be at hand.

Even though cylindrical capsules have high symmetry, they can be used for asymmetric recognition. Placement of chiral guest inside a cylindrical capsule (Fig. 2) leaves a chiral space, and that space can select between enantiomers of another molecule. The success of the recognition depends on the positioning of asymmetric elements of the 2 guest molecules near each other. This positioning can be enhanced by placing functional groups near the center of the capsule where the groups can interact with the polar residues. Currently, diastereomeric excesses are modest, about 25%, but the simplicity of the procedure promises that a large number of coguests can be screened for an optimal fit, particularly when attractive forces exist between the 2 guests.

Coencapsulation also allows the interaction of a single solvent with a solute at room temperature and in the solution phase. The capsule amplifies the interaction of the 2 guests. With unsymmetrically substituted benzene derivatives and a typical solvent, 2 isomeric forms known as social isomers exist. Their relative concentrations reflect the affinity of the smaller solvent molecule for a particular functional group on the larger solute. For example, in Figure 3, 1-pentanol prefers the polar end of N-methyl toluidine, whereas the larger benzene prefers the methyl group. Previously, these single-molecule solvation studies were limited to the gas phase at very low pressures.

Earlier, we determined that about 55% of the space in liquids is occupied by matter and that the rest is free volume. We have now made determinations for the gas phase as well. Although common gases are not encapsulated alone, the presence of a larger molecule allows coencapsulation of the gas. In Figure 3, anthracene and methane are coencapsulated. Studies with a series of gases led us to conclude that only about 40% of the space is occupied in the gas phase with these guests.

We also made progress in surrounding biological molecules in that most biorelevant of solvents: water. For example, the open-ended receptor shown on the right in Figure 3 attracts positively charged guests via electrostatic interactions with the 4 external carboxylates. The cation-¼ interactions available on the inside of the cavity subsequently draw the guest within. For acetylcholine, the limited volume of space acts as a sieve to exclude larger ammonium ions. Consequently, the selectivity for the trimethylammonium group is very high.

Publications

Ballester, P., Shivanyuk, A., Rafai Far, A., Rebek, J., Jr. A synthetic receptor for choline and carnitine. J. Am. Chem. Soc. 124:14014, 2002.

Craig, S.L., Lin, S., Chen, J., Rebek, J., Jr. An NMR study of the rates of single-molecule exchange in a cylindrical host capsule. J. Am. Chem. Soc. 124:8780, 2002.

Hayashida, O., Sebo, L., Rebek, J., Jr. Molecular discrimination of N-protected amino acid esters by a self-assembled cylindrical capsule: spectroscopic and computational studies. J. Org. Chem. 67:8291, 2002.

Hof, F., Trembleau, L., Ullrich, E.C., Rebek, J., Jr. Acetylcholine recognition by a deep, biomimetic pocket. Angew. Chem. Int. Ed. 42:3150, 2003.

Scarso, A., Shivanyuk, A., Hayashida, O., Rebek, J., Jr. Asymmetric environments in encapsulation complexes. J. Am. Chem. Soc. 125:6239, 2003.

Shivanyuk, A., Rebek, J., Jr. Isomeric constellations of encapsulation complexes store information on the nanometer scale. Angew. Chem. Int. Ed. 42:684, 2003.

Shivanyuk, A., Scarso, A., Rebek, J., Jr. Coencapsulation of large and small hydrocarbons. Chem. Commun. 11:1230, 2003.

 

 







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