encapsulation complexes are synthetic receptors that more or less completely surround
their target guests. They provide a window through which molecular behavior can
be seen in extremely small spaces. They have revealed phenomena never before observed,
such as coiled alkanes, stabilization of reactive intermediates, places where new
forms of stereochemistry can emerge, and reaction chambers with well-defined shapes.
We found that some capsules, such as shown in Figure 2, can incorporate spacer elements
known as glycolurils in response to the presence of guests. The expanded capsules
shown are present only when a suitable guest is able to fill the space inside. The
shape of the space inside is shown in the figure, and narrow functional groups such
as primary alkenes and acetylenes can fit in the tapered ends of the space.
With 2 different guests inside a capsule,
the contact points between the guests can be mapped out by using nuclear magnetic
resonance techniques. For example, with ethane and heptane coencapsulated, as shown
in Figure 3, we found that the 2 ends of heptane are alternately in contact with
the ethane. This contact is achieved by the flipping of the heptane inside the capsule, rather than by the exchange
of places of the 2 guests inside.
Cavitands With Introverted Functionality
Cavitands are open-ended molecular vessels
that allow relatively rapid motions of guests inside and out. Figure 4 shows a system
held together by hydrogen bonding that features a seam of hydrogen bonds that maintain
the vaselike shape. The cavitand is attached to an anthracene that delivers a carboxylic
acid to the inside space. We have used this system to trap reactive intermediates
such as those involved in reactions of isonitriles. The intermediates have only
microsecond lifetimes in solution but are stabilized inside the cavitand for up
to 15 minutes, long enough to characterize them by using nuclear magnetic resonance
and infrared spectroscopic techniques.
Ajami, D., Rebek, J., Jr. Gas behavior in self-assembled capsules. Angew. Chem. Int. Ed. 47:6059, 2008.
Ajami, D., Rebek, J., Jr. Longer guests drive the reversible assembly of hyperextended capsules. Angew. Chem. Int. Ed. 46:9283, 2007.
Ajami, D., Rebek, J., Jr. Reversible encapsulation of terminal alkenes and alkynes. Heterocycles 76:169, 2008.
Ajami, D., Schramm, M.P., Rebek, J., Jr. Translational motion inside self-assembled encapsulation complexes. Tetrahedron, in press.
Mann, E., Moisan, L., Hou, J.-L., Rebek, J., Jr. Synthesis of pyridazines functionalized with amino acid side chains. Tetrahedron Lett. 49:903, 2008.
Moisan, L., Odermatt, S., Gombosuren, N., Carella, A., Rebek, J., Jr. Synthesis of an oxazole-pyrrole-piperazine scaffold as an α-helix mimetic. Eur. J. Org. Chem. 10:1673, 2008.
Restorp, P., Rebek, J., Jr. Reaction of isonitriles with carboxylic acids in a cavitand: observation of elusive isoimide intermediates. J. Am. Chem. Soc. 130:11850, 2008.
Restorp, P., Rebek, J., Jr. Synthesis of α-helix mimetics with four side-chains. Bioorg. Med. Chem. Lett. 18:5909, 2008.