Chemical Synthesis A New Lab Gets It Together

ECAUSE SYNTHETIC CHEMISTS are basically chairman of the new laboratory's steering Bmolecule builders - all kinds of committee. "A lot of new science is molecules - they cross the classical bound­ emerging. " ary between organic and inorganic chemistry. Beckman Instruments, Inc., the firm that By emphasizing this commonality, the new Arnold Beckman founded 50 years ago, has Arnold and Mabel Beckman Laboratory of been an integral part of this revolution in Chemical Synthesis at Caltech makes a chemistry and chemical biology. So it's par­ significant departure from tradition, reorgan­ ticularly felicitous that a $6.5 million gift izing (one could even say synthesizing) chem­ from Arnold and Mabel Beckman made the istry in a region where organic and inorganic new Caltech laboratory possible. The firm belong together. has played an important role in the history of The new laboratory, fully stocked with world science, creating the equipment that state-of-the-art equipment in six customized science required. Although Beckman main­ labs, also reflects a revolution in the way tains that luck played a part in his company's research in synthetic chemistry is done: in the rapid growth, the phenomenal success of the past few decades it has become instrumenta­ company wasn't just good fortune, according tion-intensive. The tremendous growth in to Dervan. "As a scientist, Beckman under­ analytical instrumentation has expanded pro­ stood where science was going, and as a busi­ ductivity and precision by orders of magni­ nessman, he set out to fulfill the need that he tude, making it possible now to design and foresaw." build complex polyatomic molecules to Before Beckman was a businessman, he atomic specifications. Specific properties can taught chemistry at Caltech - and applied be designed into the molecules - properties his inventiveness to a number of other tasks with the potential for extraordinary applica­ as well. He worked with the architect and tions in medicine, industry, and research. contractor who built Crellin Laboratory of With the instrumentation available today, the Chemistry and personally helped design the Caltech research groups are developing such laboratory furnishings. He also provided cru­ novel products as new catalysts to convert cial chemical evidence in a horse-doping case simple chemicals into more complex and that resulted in the donation of the Norman valuable compounds, new enzymes W. Church Laboratory for Chemical Biology. engineered to possess useful properties not It's historically appropriate, then, that Crellin found in nature, and new molecules to trans­ (1937) and Church (1955) have now been port drugs in the body. "Synthetic chemistry reincarnated as the Arnold and Mabel Beck­ has reached a new level of sophistication," man Laboratory of Chemical Synthesis. says Peter Dervan, professor of chemistry and The idea began several years ago when

4 ENGINEERING & SCIENCE / MAY 1986 Harry Gray, the Arnold O. Beckman Profes­ visualize and manipulate these models. sor of Chemistry, was chairman of the Divi­ Although the synthetic inorganic chemists sion of Chemistry and Chemical Engineering. had modern labs in Noyes Laboratory of The synthetic organic chemists, housed in the Chemical Physics (the area into which they half-century-old Crellin Laboratory, felt their fell by tradition), they too were feeling the facilities were inadequate to keep pace with pinch. They also needed an array of equip­ the modern advances in instrumentation. ment (such as x-ray structure-analysis and They needed more instrument rooms, state­ electrochemical instrumentation) - equip­ of-the-art analytical facilities, computers, and ment that was very expensive. better safety features. And they needed such Even though they worked in separate equipment as high-performance liquid buildings, the organic and inorganic chemists chromatographs, DNA synthesizers, and were already loosely allied in a chemical syn­ high-field NMR spectrometers, as well as thesis group. The alliance had been fostered computer graphics to keep track of the hun­ by the rise of organo-metallic chemistry, in dreds of atoms in modeled molecules and to which the molecules that the researchers work

5 with are hybrids - pan organic and pan inorganic. The horderline between organic and inorganic disappears in this case. Profes­ sors Robert Grubbs (organic) and John Ber­ caw (i norganic) were both doing the same son of work in organo-metallic chemistry. work that Grubbs claims has caused him "identity problems" ever since he strayed across the artificial line into inorganic chemistry. The existence of "these two major groups that you can't put a label on," says Gray, facilitated the communicati on between the organic and inorganic chemists that led ultimately to their unification. "We've evolved to the point where we consider ourselves one communi­ ty," says Gray. The new lab "recognizes and makes fonnal what we've been doi ng for some time. We're highlighting it now. We're going to drop the labels and admit that we're all making new molecules." The old dividing line between organic and inorganic was largely a "turr' problem, ac­ cording to Gray. Whereas in the past chem­ ists were divided up into physical, organic, Celller- Pl'ler Dl'n'{U/ c/te(b inorganic, and analytical, now some chemi sts {'xper/mellta! setup ill lIell think a more rational division would be into six~roOi hood. synthesis (making molecules), chemical phys­ ics (measuring propenies and structures), and theory (applying computational techniques to says Grubbs, "and have students good enough structure and reactivity). Cal tech's effon to that they can do this son of thing - cross diminish the anificial boundaries may lead over and not get hung up on defining what the way to a new definition of chemistry sub­ they are. Our group is defined by how we groups. According to Derva n, "Already we' re think about chemistry, how we approach being sought out by synthetic chemists at problems, and also by com mon other universities who want to see what we've instrumentation. " Graduale j /lfdelll Em' . lmlYII h'orkJ ""lIh highly n'au/I'{' done." Caltech is probably the ideal place to As the molecules that synthetic chemists com/xJlllul3 ill a dry bux" change definitions. "We're small enough," build have grown more complex, the sophisti­ cated equipment they need has become more expensive, a fact that made cooperati on al­ most essential. Why not share? This also goes against the tradition that research labs have their own eq uipment, but the chemical synthesis group is quite satisfied with the con­ cept. "By getting together. pooling every­ thing, we hope to do better science," says Gray. As the orga ni c group's renovation plans began to take shape and they realized what they would need, not just to make their facili­ ti es adequate, but to playa leading role in chemical synthesis, the need for cooperation became clear. What also became clear was the need for more money than could be obtained from division funds and from grants. Arnold Beckman became interested in the project; he came out to visit with the chemical synthesis researchers and warmed to

6 ENGINEERING & SCIENCE / MAY 1986 Crellin's windows were saved by constructing Den'a" bui/ds a model of the walls for the ductwork between the designed. synthetic. seqUl'IICC­ openings. specific. DNA-binding 1I1 0/e(' lI/es \\'illl dOll ble-helical Each of the six research groups has 16 DNA. spaces for undergraduate and graduate stu­ dents and postdocs. Each research group has its own instrument room and computer room (something organic labs never had before, says Grubbs), but beyond this basic frame­ the idea. From that point on he was inti­ work, every lab is different. Each of the mately involved with planning the new faculty members (Dervan, Grubbs, Dennis laboratory. "A lot of the design - the way Dougherty, associate professor of chemistry, it's put together - came from sitting down and John D. Roberts, Institute Professor of and discussing it with Arnold Beckman," Chemistry) has customized his own. "It's a according to Gray. tremendous opportunity," says Dervan, ~ ~ to Of the Beckman gift, $460,000 per year tailor the labs for what you're doing." Der­ over five years (a total of $2.3 million) is van , for example, who shares the top floor of going toward instrumentation. Caltech will what used to be Church with Roberts, has match this with an equal amount from grants pioneered methods for understanding how and equipment funds. The rest of the gift small molecules bind and recognize a specific Bob Gru bbs inspecTs on£' 0/ was used to renovate Crellin and Church into sequence of DNA. His group needs such spe­ lite m el/ifill lilies the east and west wi ngs of the new Beckman cial equipment as high-speed centrifuges and in his lIew lab. Laboratory - a total of 46,000 sq uare feet, providing new labs for the organic synthesis faculty and students. The first phase of the lab, the top two floors of the west wing, is already complete; the three floors of the east wing will be finished in July; the last phase will be renovation of the west wing's first floor for a new senior faculty appointment yet to be made. The buildings were gulled and the new labs designed from scratch. Preserving the exterior architectural detail posed some prob­ lems that wouldn't occur in new laboratory buildings. The hood ducts, for example, are usually built into double walls in new labs, leaving them windowless. Church and

7 DNA synthesizers, as well as the high­ unusual structures in order to create new performance liquid chromatographs that are types of bonds and electronic structures. His common to the other laboratories. Roberts's quarters, which contain a large computer area of research is nuclear magnetic reso­ facility used to model bonding, are in what nance spectroscopy and its applications to used to be Crellin. problems in organic and bio-organic chemis­ Also in Crellin is the "big" instrument try (E&S January 1986), which requires a room, containing the instruments (such as different laboratory setup and such equip­ mass spectrometers) that are shared by all ment as high-field NMR spectrometers. members of the chemical synthesis group, The second floor houses three research which includes, from the inorganic side, pro­ groups that span the two wings of the facility. fessors Fred Anson and John Bercaw, assis­ In Grubbs's lab each of the 16 stations has its tant professor Terrence Collins, and Gray. own vacuum line. Besides dry boxes and Faculty offices for the organic group (includ­ infrared and ultraviolet spectrometers, Grubbs ing an office for visiting scholars) will be also has a setup he has dubbed his "molecular located all together in Crellin, giving them weight room," for determining the properties "places to run into each other." Everywhere of the polymers he builds, which have molec­ in the new lab "getting together, facilitating ular weights of up to 50,000-100,000. He communication" is emphasized; there's a shares the second floor of Church with large common seminar room and a number Andrew Myers, an assistant professor just of smaller meeting rooms. Dividing walls in hired from Harvard, whose research will be the laboratories, necessary to cut down on directed toward the synthesis of complex noise, have big windows to make the separa­ molecules of biological importance. Myers's tion less rigid. quarters cross the bridge (with the Calder Division chairman Fred Anson will have arches on the facade) between the two wings his office in the east wing (Crellin) - the and tie the two sections together; his instru­ first-floor, northeast-corner room that origi­ ment room is behind the lower level of the nally was Linus Pauling's office when he was arches. (The third floor, directly behind the division chairman. The first floor will also sculptures, will house a computer graphics contain a classroom and a stockroom. It has lab.) Dougherty and his research group con­ been exciting to Grubbs to watch it all hap­ centrate on designing and building water­ pen. "At one point a stockroom is just a soluble organic "host" molecules that contain square drawn on a piece of paper, and then a hydrophobic receptor sites. They also work couple of years later there it is. At Caltech an on the synthesis of organic molecules with idea doesn't get lost." D

Beckman Awarded Tolman Medal On April 24, 1986, the day before the dedica­ "His career properly reflects the qualities tion of the Arnold and Mabel Beckman sought in the recipient of the medal named Laboratory of Chemical Synthesis, the South­ after him. His interests were extremely ern California Section of the American broad, and he made outstanding contribu­ Chemical Society awarded its 1985 Richard tions to the development of chemistry in C. Tolman Medal to Arnold O. Beckman southern California. In addition. he served "for the invention and development of instru­ his nation well, acting in various capacities of ments that have greatly advanced the fron­ national scope and international importance." tiers of chemistry. " Tolman came to Caltech in 1921 as pro­ Nominees for the prestigious award are fessor of physical chemistry and mathematical judged for their achievements in chemistry, physics. Beckman, who had studied under significant practical applications of technol­ him at the University of Illinois, followed two ogy, and dedicated service to the profession. years later, primarily influenced in that deci­ Other Caltech recipients include Ernest Swift, sion by Tolman. The development of chem­ Arie Jan Haagen-Smit, James Bonner, John istry in southern California has clearly D. Roberts, and Harry Gray. benefited from that double migration Of Tolman the ACS local section writes: westward. D '

8 ENGINEERING & SCIENCE I MAY 1986