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