MIT Chemists Create 'Softball,' 'Jelly Doughnut' Molecules That Can Encapsulate Others


CAMBRIDGE, Mass.--Researchers in the lab of Dr. Julius Rebek, Camille Dreyfus Professor of Chemistry at MIT, have recently reported synthesizing two different cage-like molecules consisting of linked identical units that can then encapsulate smaller "guest" molecules. The work could lead to better understanding of similar naturally occurring molecules, including virus protein coats.

The results, reported in Science magazine, are a continuation of Dr. Rebek's study of self-assembling molecules and molecular encapsulation. In 1993, his lab reported the creation of a molecular "tennis ball," in which two identical C-shaped molecules, or monomers, join each other in solution at right angles by means of eight hydrogen bonds to form a hollow dimer (a molecule made of two identical subunits). This larger assembly is able to surround smaller molecules such as noble gases, methane and methylene chloride.

In the December 1, 1995 issue of Science, Dr. Robert S. Meissner, a postdoctoral fellow with Professor Rebek, reported creation of a larger self-assembling molecule dubbed a "softball." Its greater size (at 10 angstroms, nearly double the interior diameter of the "tennis ball") is a result of the monomer's longer central spacer between its two bulkier terminus units.

The "softball" can also encapsulate two guest molecules from the surrounding solution such as benzene, or one larger one such as an adamantane. The "softball" was featured on the cover of Science and was also chosen by the journal as runner-up Molecule of the Year. It came in second to the Bose-Einstein condensate, the subject of research by MIT Assistant Professor of Physics Wolfgang Ketterle (MIT Tech Talk, November 29, 1995).

Co-authoring the paper, along with Drs. Meissner and Rebek, was Dr. Javier de Mendoza of the Universidad Autonoma de Madrid in Spain, who also worked with Professor Rebek on the "tennis ball" molecule.

Robert M. Grotzfeld, a graduate student with Professor Rebek, was the first author of a January 26 Science paper describing another self-assembling molecule in which the monomer components have three termini instead of two. The resulting dimer, a flattened sphere or "jelly doughnut," is held together more strongly than the previous molecules by virtue of having 12 hydrogen bonds rather than eight. With an interior diameter of about 10 angstroms, it is capable of encapsulating disc-shaped guest molecules such as benzene or cyclohexane. Co-authors were Professor Rebek and Neil Branda, a former graduate student with Professor Rebek who is now working with Nobel laureate Jean-Marie Lehn in France.

When a new and more chemically attractive type of guest molecule is introduced into a solution containing the "jelly doughnut" and an initial guest molecule, the host molecule will "unstitch" and exchange guests, though the process can take several hours. It takes much less time for the two monomers to come together--in the case of the "softball," less than a tenth of a second, Dr. Meissner noted. The researchers can detect and record the processes of self-assembly and guest encapsulation by means of nuclear magnetic resonance spectroscopy.

One of the biggest challenges of synthesizing self-assembling molecules is building in electronic attractions and repulsions so that the monomers will assume the crescent shape that allows them to fit together in one specific way, the researchers noted. Further research may shed light on how building-block molecules "recognize" each other as they assemble.

In attempting to replicate the naturally occurring phenomena of molecular self-assembly and encapsulation on a simpler and more controlled scale, the researchers hope to gain understanding of how these processes work. "These molecules aren't biological in nature, but they mimic biology," Dr. Meissner explained. The tobacco mosaic virus, for example, assembles 2,130 identical units to build a protein coat for self-protection and transportation, resulting in a tube 3,000 angstroms in length and 180 angstroms in diameter. Hemoglobin, with four subunits, is another example; the molecule exists in assembled and disassembled forms in the body, but performs its oxygen uptake and delivery functions only when assembled.

Another application of the work is in the study of catalysts--agents that enhance the rate of chemical reactions. When two guest molecules are inside a host molecule and are thus forced into close proximity with one another, they could react more quickly, Dr. Meissner noted. Farther into the future, the research could result in a new method of drug delivery in which a self-assembling molecule encapsulates a drug molecule and carries it to the targeted area of the body. Some drug molecules are small enough to make encapsulation feasible, "but what we want to have is a system in which the host molecule recognizes only the infected cell, and we're far away from that," Mr. Grotzfeld said.

The research was funded by the National Institutes of Health.


Topics: Chemistry and chemical engineering

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