AWARDS
2005 ACS NATIONAL AWARD WINNERS Recipients are honored for contributions of major significance to chemistry
F
ollowingis thefinal'setof'vignettesof Kennedy, so as a teenager I was fascinat recipients of awards administeredby ed by space and the stars. Astronomy was the American Chemical Society for my secret love." A high school chemistry 2005. An article on George A. Olah, teacher changed his mind, and soon Nico 2005 Priestley Medalist, is scheduled laou set off for London, where he studied to appear in the March 14 issue of C&ENalong chemistry at Bedford College. He went on to earn his Ph.D. in organic chemistry with his award address. at University College, London. After post K. C. Nicolaou, winner of the Arthur C Cope Award, and most other national award doctoral stints at Columbia University and winners will be honored at an awards ceremo Harvard University, Nicolaou landed a job ny, which will be held on Tuesday, March 15, in at the University of Pennsylvania. He conjunction with the 229th ACS nationalmeet- spent more than a decade at Penn before ingin San Diego. The Arthur C. Cope Scholar moving to Scripps in 1989. awardees will be honored at the 230th ACS Today, Nicolaou, 58, "stands at the top national meeting in Washington, D.C, Aug of the field of synthetic organic chem 28-Sept. 1. istry," notes Harvard chemistry professor The Cope Award recognizes and encourages E.J. Corey He points out that Nicolaou excellence in organic chemistry; it consists of ahas forged synthetic paths to an extraor medal, a cash prize of $25,000, and an unre dinarily broad range of natural products, stricted research grant of $150,000 to be as from antitumor agents to antibiotics. No signed by the recipient to any university or re table successes include the endiandric search institution. Each Cope Scholar Award acids, amphotericin B, calicheamicin γχ1, consists of $5,000, a certificate, and an unre- rapamycin, paclitaxel, brevetoxins A and strictedresearch grantof$40,000. Arthur C B, the epothilones, vancomycin, colomCope and Arthur C Cope ScholarAwards are biasin A, bisorbicillinoids, diazonamide A, azaspiracid-1, and thiostrepton. "The sponsored by the Arthur C Cope Fund. synthesis of any one of these molecules would be the high point in the career of Arthur C. Cope Award most synthetic chemists," Corey says. "The fact that Nicolaou has synthesized A closet history buff, chemistry professor K. C. Nicolaou of Scripps Research Insti tute and the University of California, San Diego, professes a deep admiration of Alexander the Great. Nicolaou likens the qualities that have led to his own success in total synthesis to those that led to Alexander's success in battle: his perse verance, his ability to motivate war-weary soldiers, and his courage to engage even the most daunting of enemies. Nicolaou is careful to point out that he's no Alexander the Great. But Nicolaou's successful career in natural product total synthesis certainly owes much to his per sistence, his talent for motivating students "even when things look bleak," and his courage to tackle the most synthetically daunting molecules. As a kid, Nicolaou—who was born and raised in a tiny town on the northern coast of Cyprus—wanted to be an astronaut. "I grew up in the era of Sputnik and John F. Nicolaou 60
C&EN / FEBRUARY U ,
2005
all of them testifies to his extraordinary creativity and scientific ability" Nicolaou owes much ofhis success to his remarkable knack for picking interesting and highly relevant synthetic targets. "Nicolaou selects his targets carefully and with exquisite taste for unique and im posing molecular architecture," says Madeleine M. Joullié, an organic chemistry professor at Penn. "I look for molecules that have several features, including an unusual molecular architecture and some interesting biological activity," Nicolaou says. 'At the same time, I look for molecules that provide an opportunity to discover or invent new science —be it chemistry or biology" As a result, "his research delights synthetic organic chemists while being at the same time highly relevant to cutting-edge biology and medicine," notes Penn chemistry professor Ralph F. Hirschmann. Nicolaou says his favorite targets are ones that "look impossible atfirstglance." Among those that at first seemed impossible: the anticancer antibiotic calicheamicin, which features a strained bicyclic ring system containing an enediyne moiety, and the marine neurotoxic chemical brevetoxin B, a monster of a molecule with 11 fused ether rings. "The more difficult the molecule is, the more eager I am to find a solution," he says. Joullié also points out that while pursuing a given natural product, Nicolaou invariably develops new synthetic methodologies that often find far wider applications. Nearly all of Nicolaou's synthetic hunts have yielded novel synthetic strategies and new chemical reagents, beginning with his introduction of a selenium-induced cyclization reaction in the 1970s while pursuing a synthetic path to the prostacyclin class of natural products. Since then, his total syntheses have continued to yield valuable synthetic methodologies, including a variety of highly sophisticated biomimetic cascade reactions in which the product of a reaction provides the substrate for the next reaction. Nicolaou has devised elegant biomimetic cascades to make the endiandric acids (plant natural products) and the CP molecules (a pair of fungal natural products with potent antitumor activity). Not content with simply synthesizing a natural product, Nicolaou often goes on "to design and synthesize biological tools and mimics of the naturally occurring substance for biological and medical investigations," Joullié says. "His contributions reflect a new duality in the field of natural products, where the target itself affords the opportunity to create new science in HTTP://WWW.CEN-ONLINE.ORG
organic chemistry and natural-product like mimics enable exploration of prob lems in biology and medicine." Nicolaou has devised solid-phase meth ods for generating a large number of nat ural-product-like structures, each marked with a radio-frequency-encoded tag for structural identification. He's used this methodology to make libraries of analogs of the epothilones, an important class of anticancer agents; vancomycin, "the an tibiotic of last resort"; and the benzopyran class of natural products, a diverse group of biologically active molecules. All three libraries have yielded molecules of pharmaceutical interest. His achievements in total synthesis, synthetic methodology, combinatorial chemistry, and chemical biology have earned Nicolaou a slew of international awards, including the ACS Award for Cre ative Work in Synthetic Organic Chem istry, the Guenther Award in the Chem istry of Natural Products, the Tetrahedron Prize for Creativity in Organic Chemistry and the Bodossaki Prize, Greece's high est scientific honor. He is a fellow of the American Academy of Arts & Sciences and a member of the National Academy of Sciences. He's also the coeditor-in-chief ofChemistry & Biology. "But what I am most proud of is my stu dents," Nicolaou says. He has trained hun dreds of students and postdoctoral fel lows. In recognition of his mentoring skills, Nicolaou shared ACS's Nobel Lau reate Signature Award for Graduate Edu cation in Chemistry with former Scripps graduate student Phil S. Baran. He's also coauthored, with former students Erik J. Sorenson and Scott A. Snyder, two vol umes of the widely used text "Classics in Total Synthesis," which Corey calls "ex traordinarily effective pedagogic tomes." Nicolaou, ever grateful for the guidance his own early mentors provided, says he is most satisfied by the recognition that the "torch of knowledge" that he has passed on to his students burns "more brilliantly than when I received it from my own teachers."—AMANDA YARNELL
Blackmond, 46, is chair in catalysis and professor of chemistry and of chemical engineering at Imperial College of Sci ence, Technology & Medicine, in London. She "entered the field of organic chem istry from a rather unusual direction," Ja cobsen says, because Blackmond was trained as a chemical engineer with ex pertise in heterogeneous catalysis. After studying chemical engi neering at the University of Pittsburgh, Blackmond re ceived a Ph.D. in chemical engineering from Carnegie Mellon University, Pitts burgh, in 1984. Jacobsen believes this background provided Blackmond "with a completely unique and wonderfully lucid perspec tive on how to think about asymmetric catalytic reac tions," leading her "to make surprising ... discoveries Blackmond about the nature of these catalytic reactions." One example is the work she accom plished at Merck & Co., Rahway, Ν J., as associate director of technical operations from 1992 to 1995, show ing striking kinetic influ ences on enantioselectivity in Ru(BINAP)-catalyzed asymmetric hydrogénations. Blackmond has also made significant contributions to the study of nonlinear effects in asymmetric catalysis. According to Stephen L. Buchwald, Camille Dreyfus Professor of Chemistry at Massachusetts Institute of Technology, Blackmond's Borden work has "demonstrated the previously unrecognized major kinetic consequences of using nonenantiomerically pure catalysts." One such consequence is sacrificing reaction rate, often significantly, to improve optical activity. "As such, one may conclude," he adds, "that the use of nonenantiomerically enriched catalysts might not be as atArthur C. Cope tractive as has often been suggested." Scholar Awards Buchwald has collaborated with Blackmond on papers that bring valuable insights Donna G. Blackmond "is in the process of into the mechanism of transition-metalcatalyzed coupling reactions. In a recent reinvigorating the field of physical organic example, they investigated the mechanism chemistry" says Eric N. Jacobsen, Sheldon of the Pd-BINAP-catalyzed amination of Emery Professor of Chemistry at Harvard aryl halides and found that—"contrary to University "She is making discoveries of what had been proposed previously by othsuch great importance that the entire field ers and assumed by nearly everyone—oxof selective catalysis has been impacted." HTTP://WWW.CEN-ONLINE.ORG
idative addition of aryl halide does not precede amine complexation in the catalytic cycle,"Jacobsen explains. "This changes our way of tliinking about one of the most useful and widely practiced reactions of modern organic chemistry" Andreas Pfaltz, professor of chemistry at the University of Basel, in Switzerland, says he has benefited from collaboration with Blackmond "since the time we were both at the Max Planck Institute." Blackmond was group leader at Max Planck Institute of Coal Research, Mulheim an der Ruhr, Germany, from 1996 to 1999. Pfaltz comments, "I was always impressed by her strong interest in complex organic transformations and her ability to deal with structurally and mechanistic ally very complicated systems, in contrast to many other kineticists who restrict their research to simple model reactions." Among the awards that Blackmond has won are the North American Catalysis Society's Paul H. Emmett Award in Fundamental Catalysis (2001), the National Science Foundation Presidential %ung Investigator Award (1986-91), the Max Planck Society Award for Outstanding Women Scientists (1998), the Royal Society of Chemistry Award in Process Technology (2002), and the Paul N. Rylander Award of the Organic Reactions Catalysis Society (2003). Blackmond was on the advisory board of Chemical ^Engineering News from 2002 to 2004. She currently serves on the editorial advisory boards of four journals. —DEAN Ν A MILLER Asking questions pays. That could be Weston T. Borden's motto. This renowned physical organic chemist says that when he began his career, "I was convinced that I was never going to be able to answer any of the scientific questions I asked, but I kept asking anyway" As it turned out, Borden—who on Nov 1 became the first Welch Professor of Chemistry at the University of North Texas, Denton—needn't have worried. "Borden's masterful combination of the oretical insight and incisive experiments C&EN / FEBRUARY U ,
2005
61
AWARDS has made him the world's expert on the electronic structure and properties of diradicals," according to Josef Michl, who is a chemistry professor at the University of Colorado, Boulder. These compounds "play an important role in numerous or ganic thermal and photochemical reac tions," he explains. Michl adds that Borden has con tributed to many other areas of theoreti cal organic chemistry. "His results on monoradicals and radical ions, carbenes and nitrenes, cubane derivatives, phos phorus- and siHcon-containing molecules, and on the mechanism of the Cope re arrangement, and his ingenious solutions to many puzzles involving strain and smallring chemistry, substituent and isotope ef fects, reactivity comparisons, structural issues, and most recently, organometallic reactivity, have endeared him to numer ous organic chemists who find his papers readable, insightful, and useful." And Borden doesn't play it safe in those papers. "Given his penchant for publish ing untested predictions, his essentially perfect record of success over 35 years is truly remarkable," Michl notes. Borden, 61, says the computational re search in his lab "is aimed not only at mak ing quantitative predictions but also at de veloping a qualitative understanding of organic chemistry" Cornell University chemistry professor Barry K. Carpenter says Borden has a unique ability to "find the essential message in the mass of numbers that come out of a typical ab initio molecular orbital calcula tion. A journeyman theorist could carry out the same calculations—it is under standing and generalizing the results that is the creative, scholarly, and difficult part." Borden has worked with many collab orators, including Carpenter and Michl. "When I encounter results that I cannot understand," Carpenter says, "the person I call first is always Wes Borden." Michl, too, has benefited from Borden's input. "I find his intellect amazing, his en thusiasm inexhaustible, and his compan ionship enriching," Michl observes. Born in New York City in 1943, Bor den earned a B.A. in chemistry and physics at Harvard College in 1964. An M.A. (1966) and a Ph.D. (1968) in chemistry, both from Harvard University, followed in short order. He launched his academic career at Harvard University as an in structor and assistant professor. He moved to the University ofWashington as an as sociate professor in 1973 and became full professor in 1977. Two years later, while attending a con 62
C&EN / FEBRUARY U ,
2005
ference in Japan, he fell in love with the coun try Borden and his family have returned for several extended stays. He celebrates spe cial occasions by hostingjapanese tea cere monies and also practices Japanese flower arranging. Borden is drawn by the sim plicity and lack of clutter of the Japanese aesthetic— qualities that also character ize the type of chemistry conundrums he chooses to work on. He notes that the key to solving these prob lems is first, to "recognize that there's a question to be asked," and then to "ask the question in away that makes the answer obvious. That's Cravatt the hard part!" Borden's honors include fellowships from the Guggenheim and Humboldt Foundations and the Japanese Society for Promotion of Science.—SOPHIE ROVNER The fields of enzymology and proteomics might have been different had Benjamin F. Cravatt III run just abit faster in the 1993 Portland Marathon. While he was a grad uate student at Scripps Research Institute, Cravatt, a lifelong runner but never a marathoner, made a bargain with himself: "I promised myself if I could run it in 2 hours and 26 minutes—four minutes off the Olympic qualifying time—I'd postpone grad school and train for the Olympics," Cravatt says. He turned in a time just four minutes shy of his goal and replaced his Olympic dreams with scientific ones. Now a professor of cell biology and chemistry at Scripps, Cravatt, 35, can't imagine doing anything else. "Everyday I learn something new," he says. Born in Houston and raised in Los An geles, Cravatt went to college at Stanford University hoping to become a physician. He majored in both history and biology, but when his undergraduate mentor urged him to try research, he ended up doing pep tide chemistry with bioorganic chemist John H. Griffin. "I had no idea what re search was about when I went to college," Cravatt says. "This experience turned me on to a research career." He quickly de cided to go to graduate school, applying mostly to biology programs but also to Scripps's then-nascent Ph.D. program "be cause it dedifferentiated between chem istry and biology" As a graduate student, Cravatt initially designed catalytic antibodies in Richard A. Lerner's lab. Itching to do more discoverybased research, Cravatt later switched gears
and began tracing the biochemical fate of oleamide, a fatty acid amide lipid that in dicates an organism's need for sleep. His quest led him to discover and characterize fatty acid amide hydrolase (FAAH), a novel mem brane-associated enzyme that controls the levels of oleamide and related signal ing lipids in the brain. Soon after he earned his P h D . in 1996, Cravatt was offered a faculty job at Scripps's newly opened Skaggs Institute for Chem ical Biology There, Cravatt has continued to explore the structural, functional, and physiological properties of FAAH. His lab has revealed FAAH's unusual catalytic mechanism, characterized its structure via X-ray crys tallography and created mice that lack the FAAH enzyme. His analysis of the physiological effect of knocking out FAAH in mice has re vealed that this enzyme is the "off switch" for fatty acid amide signaling in vivo. Cra vatt suggests that FAAH may be an at tractive pharmaceutical target for the treatment of pain and neuropsychiatrie disorders, and his structural and functional studies point to ways to design potent and selective FAAH inhibitors. Cravatt's work with FAAH inspired his lab's second major thrust: the design of a chemical strategy to determine which en zymes in a given cell are active, regardless of their abundance. Standard proteomics techniques simply measure the abundance of proteins in specific cells or tissues and fail to detect which of these proteins are active. To overcome this limitation, Cra vatt developed a method—dubbed activ ity-based protein profiling—that relies on active-site-specific reagents to capture ac tive members of particular enzyme fami lies in complex proteomic mixtures. Cravatt hopes to come up with a menu of chemical probes that will allow dynamic profiling of the hundreds to thousands of enzymes that are active in a given cell or tissue. So far, he's developed activity-based probes for more than 10 different enzyme families. Cravatt—with ActivX, the com pany he founded to commercialize the technology—is using these probes to dis cover novel disease-related enzymes. "Cravatt has shown the two facets of a scholar who will change the standards in the field," comments Christopher Τ Walsh of Harvard Medical School. "The first is deep scholarship and commitment HTTP://WWW.CEN-ONLINE.ORG
to high experimental standards. The second is creativity and nonlinear thinking." Walsh notes that Cravatt's novel chemical method for sorting out the complexities of the proteome typifies his creative approach to problems.—AMANDA YARNELL Huw M. L. Davies has rapidly emerged as a major contributor to synthetic methodologies and asymmetric catalysis involving metal carbene intermediates. His work has resulted in new, highly efficient strategies for the construction of complex chiral molecules. He has focused on the chemistry of donoracceptor-substituted rhodium-carbenoid intermediates and their application to the design of new practical catalytic methods for enantioselective transformations. Davies'group developed a general method for the synthesis of seven-membered rings through the Davies rhodium-catalyzed decomposition of the appropriate diazo compounds. Predictable control of stereochemistry is possible because the reaction proceeds through a two-step mechanism, which is cyclopropanation followed by a Cope rearrangement. He also found that dirhodium tetraprolinates can function as exceptional chiral catalysts for the donor-acceptor-substituted carbenoids. His methods have achieved impressive turnover numbers, and the immobilized catalysts can be recycled many times without loss. The firstgeneration catalysts are now commercially available. Davies, 48, is a native of Wales. After undergraduate studies at University College Cardiff (now Cardiff University, Wales), he received a Ph.D. in organic chemistry from the University of East Anglia, England, in 1980. Davies began his research with catalytic metal-carbene chemistry as a postdoc in E. C. Taylor's laboratory at Princeton University He remained in this field as he established his academic career, first at Wake Forest University, Winston-Salem, N.C., and then at the State University of New^brk, Buffalo, where he is now Larkin Professor of Organic Chemistry "When I began my academic career, I expected our studies into rhodium carbenoid chemistry to last just two or three years, but this has not been the case," Davies recalls. "Instead, the chemistry has been full of surprises and has continued to HTTP://WWW.CEN-ONLINE.ORG
open exciting new avenues for synthesis." In the past few years, Davies has shown that intermolecular C - H insertion ofrhodium carbenoids is arguably the most general method to date for catalytic enantioselective C - H activation. Prior to his work, asymmetric C - H insertions were limited to intramolecular versions because the standard rhodium-carbenoids were too reactive andunselective for application toward practical intermolecular C - H insertions. Davies found that donoracceptor-substituted carbenoids have a very different reactivity profile from that of conventional carbenoids. Much more stable, substituted carbenoids display greater chemoselectivity than conventional carbenoids and are capable of effective intermolecular C - H activation. Having designed effective and reliable catalysts, the Davies group developed a series of useful catalytic enantioselective transformations that have been employed in the synthesis of complex natural products and pharmaceuticals. These transformations include enantioselective C - H activation, combined asymmetric C - H activation/Cope rearrangement sequences, and {3 +2]- and [4 +3]-cycloaddition reactions. Use of these transformations has allowed his group to expand into multidisciplinary research, such as the design of neuroimaging agents and the development of medications for cocaine addiction and other central nervous system disorders. "Davies' pioneering work in the asymmetric functionalization of unactivated C - H bonds is of fundamental importance. It opens the Ismagilov door to entirely new types ofchemical reactions, and it has led to commercially important products. It is rare when one's research wins such a trifecta," a colleague says.—MELISSA BRADDOCK T h e overarching theme of Rustem F. Ismagilov's research is using microfluidic devices to control complex reaction networks in space and time, thereby maintaining them for study far from equilibrium. Such networks provide potential models for a variety of processes in living systems. "There is a gap between organic chem-
istry as we teach it and biology," says Ismagilov, an assistant professor at the University of Chicago. "In principle, all biology is just organic chemistry, but in fact there is something magical separating biology from organic chemistry." Biology emerges from the complexity of networks of organic reactions, Ismagilov says. Ismagilov inspires both professional and personal accolades from mentors and colleagues. In addition to being described as a brilliant and innovative physical organic chemist, he is often described as "sincere," "modest," and "a leader." Harvard University chemistry professor George M. Whitesides, with whom Ismagilov did a postdoc, says Ismagilov "is absolutely first-rate—someone who is certain to be at the top of the chemical profession and to be one of the people who lead it into new areas. He is very imaginative, committed to science, hardworking, efficient, modest, and unafraid of unconventional and difficult problems. He is also an entirely decent person." Ismagilov's education seems to have led inevitably to his current research interests. WHtesides points out that Ismagilov received his B.Sc. in chemistry in 1994 from the Higher Chemical College of the Russian Academy of Sciences, in Moscow. As a result, Whitesides says, Ismagilov "is very strong in applied mathematics, which gives him a real advantage in some of the types of work he is doing. His ability in mathematics is very unusual for an organic chemist." Ismagilov received his Ph.D. in 1998 withStephen F. Nelsen from the University of Wisconsin, Madison, where he worked in classic physical organic chemistry primarily in electron transfer and the chemistry of radical cations derived from hydrazines. In WTiitesides' lab, he worked in two areas: laminar flow in microfabricated capillaries and complexity Two areas of research have been pursued in Ismagilov's lab since he arrived at Chicago in 2001, both involving microfluidic devices. One is the development of a device that makes microdrops containing two or more liquids suspended in a second fluid. In these devices, submillisecond mixing can be achieved. The devices have been used to control reaction networks in time, to measure millisecond kinetics, and for protein crystallization. The other area has been the developC & E N / FEBRUARY U ,
2005
63
AWARDS ment of a minimal function model of hemostasis —that is, blood clotting—in a biomimetic microfluidic system [Angew. Chem. Int. Ed., 43,1541 (2004)}. In this re search, Ismagilov and coworkers showed that hemostasis, which consists of ap proximately 80 coupled biochemical re actions, can be successfully modeled with only three reactions. In ad dition to providing insights into how hemostasis may have evolved from a rela tively simple system into the complex system that ex ists today, the research has provided a microfluidic sys tem for studying hemosta sis involving real blood. "The microfluidic de vice is our round-bottom flask," Ismagilov says. "It is a tool we are still developing and making better and en- Iverson joying all the things it allows us to do. I cannot stress enough that this work is being carried out by a very talent ed group of students and postdocs work ing in my lab. "One might ask, this being a Cope Scholar Award, what this has to do with or ganic chemistry," Ismagilov says. "My view is that organic chemists have become in credibly adept at synthesizing molecules and in using physical organic chemistry to determine how they behave. We are doing something very similar with networks of reactions, using many of the same princi ples to understand them." Although it is early in his career, Is magilov has already received numerous awards and honors, including a National Science Foundation CAREER Award (2004) and the 2001 Camille & Henry Dreyfus New Faculty Award. In 2003, he was named a Beckman^ung Investigator, an Office of Naval Research Young In vestigator, and a DuPont Young Profes sor. In 2002, he was a Searle Scholar.— RUDYBAUM
"I am an organic chemist at heart," says Brent L. Iverson, a professor in the de partment of chemistry and biochemistry at the University ofTexas, Austin. "In the end, even when working with large pro teins or nucleic acids, I always care about all of the atoms—including the hydrogens." Nevertheless, along with recently pub lishing an organic chemistry textbook and more than a decade of teaching organic chemistry Iverson is cofounder, along with George Georgiou, of a protein engineer ing lab at the university's Institute for Cel 64
C&EN / FEBRUARY U ,
2005
lular & Molecular Biology He estimates that currently three-quarters of his re search is built around protein research. For nearly 20 years, he has worked at the interface of bioorganic chemistry and molecular biology The common theme, he explains, has been folding and assem bling large molecular systems in water. The foundation of his research is the belief that a logical direction for organic chemistry is the realm of large molecules, including entirely synthetic systems, natural proteins, and nu cleic acids. In a 1995 Nature article, Iverson was one of the first chemists to describe an abiotic synthetic folding molecule, later termed a "foldamer," and he was the first to describe a synthetic folding system in aque ous solution. Aromatic donor-acceptor in teractions, which provided the basis for folding in Iverson's synthetic systems, have proven to be especially powerful in water, and he has been systematically exploring their use for folding, assembly, and even D N A binding. Aqueous solutions are a hallmark of his research. Rather than using organic sol vents, he says, he uses water because it provides an envi ronmentally friendly medi um and enables interactions with biological structures and molecules to be studied as part of an integrated mo lecular system. Ifa chemistry works in water, Iverson be lieves it stands a much bet ter chance of being impor tant down the road, when environmental concerns will be even more compelling than they are today Knοch eI Iverson's protein engi neering lab has focused on developing new technologies to enhance protein function, initially antibodies. The lab's research has led to development of an engineered an tibody for use as an antidote for anthrax. Two years ago, the antibody was patent ed and licensed to the New Jersey com pany Elasys. Aversion of the same patent ed technology used to improve the anthrax antidote antibody has more recently been applied to modulate enzyme substrate specificity, taking the Iverson lab into the area of biocatalysis engineering. Iverson, 44, got his start in chemistry
as an undergraduate inJames P. Collman's lab at Stanford University He received his doctorate from California Institute of Technology, where he studied under chemist Peter B. Dervan. He did post doctoral work at Scripps Research Insti tute with Richard A. Lerner. All three pro fessors, Iverson notes, were early leaders in chemical-biological research. Along with research, Iverson says, teaching is quite important to him, as is his membership in the University of Texas Academy of DistinguishedTeachers. "This is a public university, and it's here to edu cate the citizens of Texas as well as carry out important research," he notes. He predicts that his future research will draw him deeper toward applications, and for synthetic systems, that means into ma terials sciences. "We are looking at mate rials in every sense of the word," he says, adding that he will continue exploring the use of organization based on molecular folding as well as the use of noncovalent intermolecular interactions to create new properties.—JEFF JOHNSON Paul Knochel can trace his passion for organic synthesis to his schoolboy days in Strasbourg, France. As a young chemist working in his homemade labo ratory, Knochel loved to transform foulsmelling carboxylic acid compounds in to sweet-smelling esters. T h e 49-year-old chem istry professor at Munich's Ludwig-Maximilians Uni versity also remembers how he once raised his father's ire by washing his glassware in the kitchen after one of these early experiments. The strong fruity smell of the butyl butyrate he had made that day permeated the kitchen and ruined the dinner that his m o t h e r was cooking. Knochel soon graduated to more auspicious experiments. After fin ishing his undergraduate studies at the Uni versity of Strasbourg, he earned his Ph.D. at the Swiss Federal Institute ofTechnolo gy, Zurich, under the guidance of Dieter Seebach. Knochel then returned to France, only to find that his native country did not recognize his Swiss Ph.D. Unfazed, Knochel decided to pursue a second doc toral degree withJean-François Normant at Paris' University Pierre & Marie Curie. He followed this with a year of postdoctoral study with Martin F. Semmelhack at Princeton University before taking an assistant HTTP://WWW.CEN-ONLINE.ORG
professor's position at the University of Michigan. Knochel moved to Marburg, Germany, in 1992 to take a post at Philipps University and in 1999 he moved to his cur rent position in Munich. While he was working in Seebach's lab, Knochel took note of the new titaniumbased reagents that some of his colleagues were developing. "I was very impressed by this work," he says, "but I thought one of the drawbacks was that you couldn't do this chemistry with functionalized organics." Then, while studying in Paris, Knochel noticed that organozinc com pounds could tolerate functional groups that other organometallics could not. These two events, Knochel says, mark the beginning ofhis distinguished career in venting and developing zinc-, magnesium-, and copper-based organometallics that bear functional groups previously thought to be too labile to be part ofan organometallic compound. The organometallic reagents he has developed over the past 15 years bear cyano, phosphonate, and α-oxygen func tionalities, to name a few. Some of the organozinc compounds even carry relative ly acidic C H protons. "These new organometallic reagents considerably increase the scope of organ ometallic chemistry for organic synthe sis, avoiding many protection-deprotection steps in complex organic syntheses," remarks Ilan Marek, a chemistry profes sor at Technion-Israel Institute of Tech nology, in Haifa. Bruce H. Lipshutz, a chemistry professor at the University of California, Santa Barbara, adds, "It is hard not to find references to Knochel proce dures in essentially any journal that caters to organic chemistry" Along with his extensive work on organometallic reagents, Knochel has de veloped new synthetic methodologies for organometallic reactions, asymmetric synthesis, and stereoselective radical chemistry "Knochel is not interested in following the latest fashions of organic chemistry but instead tries to create his own original fashion," comments Univer sity of Chicago chemistry professor Hisashi Yamamoto. Marek adds: "Paul is blessed with a very fertile imagination and a great sense ofwhat will and will not work. His productivity is simply outstanding, and the range and scope ofhis work are nothing short of inspirational." Although chemistry keeps Knochel busy, he admits that he has a real passion for photography In fact, his first published photograph will appear on the cover of Angewandte Chemie this year. —BETHANY HALFORD
HTTP://WWW.CEN-ONLINE.ORG
Referred to by his colleagues as a "tow ering figure" in the field of organic pho tochemistry, Frederick D. Lewis, 61, credits much of his success to fruitful collaborations. Lewis first became fascinated by the in teraction of light with molecules at a sum mer job after graduating with a bachelor of arts in chemistry from Amherst College, in Massa chusetts. He worked in a group at American Cyanamid looking for practical applications for p h o t o chromic spiropyrans. Lewis went on to earn a Ph.D. in organic chemistry at the University of Roch ester in the laboratory of William H . Saunders Jr., where he studied azide pho tolysis. After a postdoc at Columbia University with Lewis Nicholas J. Turro, he joined the Northwestern University faculty in 1969, where he is currently professor of chemistry Michael R. Wasielewski, a colleague in the Northwestern chemistry department, says that one of Lewis' earliest contribu tions to photochemistry came through his study of α-cleavage and γ-hydrogen abstraction from alkyl and cycloalkyl phenyl ketones. Lewis "helped mold the way chemists think about excited-state reactivity" by showing that these excit ed-state processes were governed by tran sition-state theory concepts. Lewis fur ther shed light on the excited state by establishing that excited-state complex es, including excimers and exciplexes, and radical ions can be intermediates in pho tochemical reactions. Lewis says one of the features that in trigues him about the excited state is that it can be approached using a combination of theoretical studies, spectroscopic stud ies, and chemical studies. He takes advan tage of all three approaches by forging a broad range of collaborations with spectroscopists, theoreticians, and synthetic organic chemists. "He adapts diverse meth odologies" through those collaborations, Wasielewski says, which permit him to "tackle highly complex problems." Lewis' well-known study of D N A elec tron transfer is a fine example ofhis abil ity to create successful collaborations. While Lewis was serving on the board of editors for nit Journalof theAmerican Chem ical Society, he observed the budding con troversy over whether D N A acted as a molecular wire.
"Lewis was one of a handful of scientists well positioned to assess the claim that DNAis a molecular wire," remarks Gary B. Schuster, professor ofchemistry at Georgia Institute oflechnology. Lewis' earlier work on exciplexes, as well as his creativity in or ganic synthesis, Schuster says, led to "a bril liant set of experiments using DNA hair pins formed with loops composed of light-trig gered, one-electron oxi dants or reductants." Design and synthesis ofthe hairpins and analysis of the experi ments were possible only through collaborative work with synthetic chemist Robert Letsinger, spectroscopist Wasielewski, and biochemist Martin Egli, all at Northwestern. DNA, it turns out, is no wire, al though it transfers electrons better than proteins do. Last year, Lewis' contributions to pho tochemistry were recognized with the dedication of an issue of the international journal Photochemical & Photobiological Sciences for Lewis' 6 0 t h birthday. He was also given the 2003 Award in Photo chemistry from the Inter-American Pho tochemical Society and this year, in addition to the Cope Scholar Award, he received the Northwestern Alumni Association's 2004 Excellence in Teaching Award. Wasielewski notes that in the past year, Lewis has made further significant con tributions to D N A molecular photonics and the photoisomerization reactions of aryl olefins. "Rather than becoming pre dictable or slowing down, Fred remains at the cutting edge of organic photochem istry"—LOUISA D ALTO Ν Steven M. Weinreb, Russell & Mildred Marker Professor of Natural Products Chemistry at Pennsylvania State Univer sity, has focused his career on the devel opment of new synthetic methods and to tal synthesis of natural products. Hailing from N e w a r k City, Weinreb received his bachelor of arts degree from Cornell Uni versity in 1963 and a Ph.D. from the Uni versity of Rochester in 1967. Postdocs at Columbia University and at Massachu setts Institute of Technology were fol lowed by his first post as assistant profes sor of chemistry at Fordham University, 1970-75, and as associate professor of chemistry, 1975-78. In 1978, he moved to Penn State as an associate professor of chemistry, and he has been there ever since. Weinreb beC & E N / FEBRUARY U ,
2005
65
AWARDS came professor of chemistry in 1980, and in 1987 he was named Marker Professor, a chair he continues to hold. He was also head of the department of chemistry for four years, from 1994 to 1998, and interim dean of Eberly College of Science at Penn State in 1998. Weinreb has made a number of seminal contributions to the field of synthetic organic chemistry during his career. One colleague says, "His research can best be characterized as the development of innovative and broadly useful synthetic methodology, which is then elegantly ap- Weinreb plied to the total synthesis of structurally complex natural products." He has achieved several notable total syntheses during his career, including the natural products cephalotaxine, methoxatin, streptonigrin, 7-epicylindrospermopsin, and olivin. His cephalotaxine synthesis, this colleague says, is still considered "the most efficient route to this unique alkaloid, which is of potential value in cancer chemotherapy "The streptonigrin project utilized an imino Diels-Alder reaction as a key step and was the impetus for the future development of groundbreaking hetero DielsAlder methodology He has pioneered the development and application of hetero Diels-Alder chemistry in organic synthesis, and he coauthored, with Dale L. Boger of Scripps Research Institute, a widely cited book on the subject. Weinreb has shown that cycloadditions using imino and N-sulfinyl dienophiles are valuable in the synthesis of diverse types of nitrogen heterocycles and alkaloids. Weinreb has also invented several general methods that have been widely adopted by the synthetic community Perhaps his best known methodology involves use of so-called Weinreb amides in acylation reactions. In addition, he has demonstrated that aluminum amide reagents of various types are valuable in converting esters to amides and nitriles. Another colleague says Weinreb has a knack for selecting targets. "He is a nononsense guy who easily and quickly dispenses his work and completes the task at hand," the colleague says. "His naturalproducts total syntheses, his methodology development, and his approach to science are practical and bear a signature creative solution to a challenging practi66
C&EN / FEBRUARY U .
2005
cal problem," involving a target "of contemporary or practical importance." Weinreb was president of the International Society of Heterocyclic Chemistry in 2002-03. He was also a senior editor of the Journal of Organic Chemistry from 1990 to 1997, among other editorships. In addition to a host of publications, Weinreb has built up a distinguished list of invited and plenary lectures to both universities and corporations, particularly pharmaceutical companies. Some of the most recent have taken him to South Korea, Japan, Canada, the U.K., and N e w Zealand, as well as to various locations in the U.S. —PATRICIA SHORT Although he is receiving one of organic chemistry's highest honors, J a m e s D. Wuestp 56, thinks t h a t many people would be surprised to learn that he nearly skirted disaster in his academic career. Wuest studied under Roald Hoffmann when he was an undergraduate at Cornell University and did his doctoral work with Robert B. Woodward at Harvard University. So it might have seemed that Wuest was predestined to take a smooth path to a successful career in chemistry Not so, according to Wuest: "I struggled a bit as ayoung professor. I had trouble turning ideas into concrete projects," he says. "I think it's fair to say that my survival in academics, and even in research, is something that wasn't guaranteed." The turning point, Wiiest says, came in 1981, when he joined the chemistry department at the University of Montreal, where he currently holds the Canada Research Chair in Supramolecular Materials. And, as a scientist working in Canada, Wuest Wuest is particularly proud ~~ that he's been singled out by the American Chemical Society He acknowledges that the move was a gamble at the time. The school's official language is French, and even though Wuest spoke no French when he accepted the position, he was expected to conduct courses in that language. Even with the language barrier, Wuest found the opportunity too good to pass
up. He was particularly attracted to the way that Canadian funding agencies support science. In Canada, he explains, it's easier to find support for long-range projects. "Grant renewal is more about developing a career than short-term results," Wuest says. "Some of the things I wanted to do in science, I thought, would take a particularly large amount of time." More than 20 years later, it's clear that Wuest has managed to master these longrange projects along with the French language. His distinctive research, which reaches into the fields of supramolecular chemistry and materials science, aims to use weak interactions in order to control molecular association. For example, he pioneered the synthesis and study of multidentate Lewis acids—compounds with multiple Lewis acidic sites that can be strategically placed to recognize, bind, and chemically activate molecules with complementary arrangements of basic sites. "The contributions that Wuest and his group have made to our understanding of the coordination chemistry of complex Lewis acids reveal a flair for designing and synthesizing novel molecules and an ability to work creatively with a large part of the periodic table," remarks Stephen Hanessian, a colleague of Wuest's at the University of Montreal. "Wuest's designed acid catalysts are among the most thoughtful physical organic chemistry that has been done in this area," adds George M. Whitesides of Harvard University "He is not following anyone. He has produced ideas, based on his own imagination, that are making a substantial difference." Wuest has also been working in the area of molecular tectonics, in which organic building blocks are used to design and engineer the structure of crystals. According to Steven C. Zimmerman, a chemistry professor at the University of Illinois, Urbana-Champaign, "Wuest's early use of ~~ directed hydrogen bonding to control aggregation in solution and molecular solid-state packing in crystals had an enormous impact on researchers in the field and inspired a legion of new researchers to enter the field of crystal engineering."The research has led to hydrogenbonded networks with exceptional porosity and robustness, crystal engineering with subnanometer precision, and highly deformable crystals.—BETHANY HALF0RD HTTP://WWW.CEN-ONLINE.ORG
