ALLISON L. BYRUM,C&EN WASHINGTON

COURTESY OF UCLA

In 1987, in his 69th year, Donald J. Cram received the Nobel Prize in Chemistry from King Carl XVI Gustaf of Sweden. Uncharacteristically dressed in a tuxedo, the usually casual scientist graciously represented the University of California, Los Angeles, and the U.S. on the world's stage. Cram, however, did not view the Nobel Prize as the culmination of his career. The ceremony was simply a temporary distraction, but one that was accompanied by a prize that allowed him to continue his work.

J. Fraser Stoddart, Saul Winstein Professor of Chemistry at UCLA, recalls Cram commenting that he felt "privileged to be born into a time when a large number of people, taxpayers, were willing to pay for him to practice his hobby."

Cram's "hobby" was revolutionizing organic chemistry. Upon his death from cancer on June 17 at age 82, Cram had spent more than 50 years at UCLA pursuing that hobby, with an intensity that only increased with every passing year.

Cram's youth was spent in rural Vermont. When he was four, his father died, leaving Cram the man of a house that included four sisters and his mother. Cram was a happy and playful child. In the autobiography he penned following receipt of the Nobel Prize, Cram wrote that his sisters recalled a young boy always curious and frequently causing or getting into trouble.

His childhood interests ranged from rough-and-tumble outdoor sports to reading the works of Dickens, Kipling, and Shakespeare. To aid his family, Cram acquired numerous odd jobs, including shoveling snow, picking apples, and mowing lawns. His resourcefulness and hard work resulted in his having had 18 different employers by the time he was 16 years old.

Cram graduated from Winwood, a small private school on Long Island, and earned a four-year scholarship to Rollins College in Winter Park, Fla. It was at Rollins that he decided to pursue chemical research. He once commented: "When I first heard the word 'research,' it meant to me that the only limitations are your own resourcefulness and creativity, and that was precisely what I wanted."

 FROM ROLLINS, Cram's interest in chemistry and research took him through master's work at the University of Nebraska, a stint as a research chemist at Merck, and on to a Ph.D. from Harvard University, before he joined UCLA in 1947.

Cram's energy pervaded his early work. The same mischievousness that marked the little boy infused the work of the chemist. Always smiling with a twinkle in his eye, the tall scientist filled a room with his enthusiasm. M. Frederick Hawthorne, University Professor of Chemistry at UCLA and Cram's fifth Ph.D. student, remembers that enthusiasm and vigor spreading contagiously through his students and colleagues.

Cram began his career at UCLA under Saul Winstein, who had a strong influence on his work. Cram soon made a name for himself with the discovery of phenonium ion intermediates, his work on the stereochemistry of sulfur compounds and cyclophanes, and asymmetric induction (Cram's rule). Variations on this work took Cram to the forefront of carbanion chemistry.

"When I first heard the word 'research,' it meant to me that the only limitations are your own resourcefulness and creativity, and that was precisely what I wanted."

EYES ON THE PRIZE Cram received the Nobel Prize in Chemistry from King Gustaf of Sweden in Stockholm on Dec. 10, 1987; a young Cram sketches structures on a blackboard, early evidence of his predilection toward visual representations and models. PHOTOS COURTESY OF UCLA

In 1959, Cram, with George S. Hammond of California Institute of Technology, published a textbook called simply "Organic Chemistry." One of his seven books, "Cram and Hammond" (as it became known), revolutionized the teaching of the subject by reorganizing the presentation of organic chemistry.

By the 1960s, Cram had already earned a reputation as a respected organic chemist. His work on carbanions and stereochemistry was well known. However, this phase of his career proved to be only an introduction to the revolutionary changes Cram made in his field.

Cram was "my chemistry hero," says Kendall N. Houk, professor of chemistry at UCLA. "He'd take unusual ideas, stick with them, and convert them into reality." One of these "unusual ideas" was host-guest chemistry, born out of a class of macrocyclic polyethers called "crown ethers" that was first described in the literature in 1967. Cram immediately recognized the significance of such molecules and, in a stunning career move, decided to make them the focus of his research.

"People were astounded and skeptical," Houk explains, "but he had the fortitude and passion to pull it off and synthesized quite unusual things."

The field of host-guest chemistry suited Cram ideally. It was innovative, challenging, and required massive amounts of creativity and determination. Cram seemed to be endowed with an endless supply of both.

Cram viewed scientific research as the "last bastion of real challenge," Stoddart explains. He valued creativity highly and felt that research granted him opportunities to be more creative "than any painter, artist, musician, or sculptor." Stoddart points out that Cram was a sculptor. His medium was not clay or stone, but atoms and molecules; his tools were not chisels, but the plastic molecular models that were constantly by his side--models that helped him work out the problems of host-guest chemistry.

Cram recognized the power of visual representations; his more than 400 handwritten manuscripts not only reflected his extensive knowledge of literature but were always well illustrated. Using his deep understanding of three-dimensional space, Cram set about building, first as models, then as molecules, synthetic hosts that attracted and bound specific guest molecules. Some of these host-guest complexes are designed to mimic the actions of enzymes.

FOR HIS WORK on host-guest chemistry, Cram shared the Nobel Prize with Jean-Marie Lehn of Louis Pasteur University and Charles J. Pedersen of DuPont. What had been perceived as a risky career move proved to be anything but.

In a chapter on supramolecular chemistry in "The New Chemistry" (see page 43), Lehn and chapter coauthor Philip Ball explain Cram's contributions to host-guest chemistry. In the beginning, host-guest chemistry involved designing circular chains of ethers to surround another species, usually a metal ion. Depending on the physical properties of the ether ring, or host, species of different sizes and shapes can serve as guests. Cram advanced the field by adding rigid benzene rings to the host structures so that the binding of guests required less energy. Cram and his colleagues succeeded in designing and synthesizing more than 1,000 chemically and physically unique hosts.

Cram's love of a challenge was evident in every aspect of his life. Outside of the classroom and his laboratory, Cram loved to surf, play tennis, snow ski, and swim. In every instance, he tackled the sport as if he were competing. Stoddart notes that his biggest competitor was himself. "When he swam laps in the pool, Cram would set high goals for himself--X laps in Y minutes. When he played tennis, he trained under the top tennis coach at UCLA. In every task he undertook, he worked hard to become even better."

Surfing was a passion. Stoddart recalls the surfing pictures Cram often used at the end of lectures to relate scientific challenges to surfing. The relationship between the board and the water embodied competition for him, and he often described how, in his research, he liked being "on the crest of a wave." One wave was never enough, however, and Cram was not content to end his adventure with a Nobel Prize.

FOLLOWING HIS Nobel Prize, Cram further advanced the field of organic chemistry with the inception of "carceplex" chemistry. The process involves one molecule encasing another.

Carceplex chemistry grew out of his previous work in host-guest chemistry. Cram's original structures, Lehn explains, were rigid rings that bound a guest but left it exposed to an outside solution. Carceplexes involved two cup-shaped molecules lined with hydrophobic benzene rings and joined together. The result is a molecular prison called a carcerand. When a molecule becomes trapped inside a carcerand, the complex is called a carceplex.

Cram took the carceplex concept one step further and created hemicarcerands, which are characterized by a small gap in the wall of the carcerand. Molecules can travel through this gap only if the temperature is high enough. Once inside, however, the molecules cannot escape if the temperature has been lowered.

JAIL CELL Cram found this carcerand could imprison a number of species.

The ultimate test of hemicarcerands came when Cram allowed a molecule of a-pyrone to pass into the carcerand cage. Inside, the a-pyrone underwent a photochemical reaction, yielding cyclobutadiene. Under normal conditions, cyclobutadiene is so highly reactive that it cannot be isolated or studied. Cram's carceplex, however, kept it from reacting and allowed the molecule to be observed for the first time.

Hawthorne says, "I view carceplexes as the culmination of Cram's career--the finest thing he ever did."

Carceplex chemistry has allowed chemists to capture and study other unstable molecules such as benzyne and cycloheptatetraene for the first time. Ronald Breslow, chemistry professor at Columbia University, praises Cram for his inventiveness. He characterizes carceplex chemistry as a "completely original and exciting creation of molecular containers--a brilliant post-Nobel contribution."

Cram had an enormous impact on organic chemistry worldwide. François Diederich of the Swiss Federal Institute of Technology, Zurich, describes Cram as an excellent coach and mentor to students and fellow faculty. According to Diederich, there is an international "Cram school," bearing the hallmark of Cram's continuous search for innovation, originality, and quality.

Diederich recalls Cram explaining his "dreams for science and for chemistry in particular." He says of his hero, Cram "has abundantly shown that these dreams never abandoned him and that he had the skills and vision to transpose them into reality."

Cram's life will be celebrated with a symposium at UCLA on March 28–30, 2002, titled "Fifty Years of Cram's Rule: The Chemistry and Chemical Legacy of Donald J. Cram." Houk and his colleagues are also planning a gathering on Oct. 8 to "remember Don and share stories of him and his impact on all of our lives." For additional information on either event, contact Houk at houk@chem.ucla.edu or at (310) 206-0515.

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Copyright © 2001 American Chemical Society