COVER STORY
CHEMISTRY HIGHLIGHTS 2003 Key advances were reported this year across a broad span of chemistry subdisciplines, ranging from carbohydrate chemistry to surface science
STU BORMAN, C&EN WASHINGTON
A
STEADY STREAM OF NEWS ON THE LATEST CHEMI-
cal research developments flows by us with dizzying speed all year, every year. In C&EN's annual Chemistry Highlights, we recall some of the impressive advances we've reported on during the year. In selecting developments to be included in this year-end review, we look for studies that have an identifiably superlative quality or element of uniqueness—such as the first time something was done, an order-of-magnitude improvement, or a capability that was just not possible before. Our list is meant to be representative, not comprehensive. So we're by no means implying that it's not important if it's not here. Our hope is merely that our selections, when considered as a HTTP://WWW.CEN-ONLINE.ORG
whole, help provide greater perspective on the enormous scientific and technical strides—and consequent benefits to society—made by the chemistry research enterprise each and every year. ORGANICS & CARBS. Exemplifying new organic reactions devised this year, Noritaka Mizuno of the University of Tokyo and coworkers developed a hydrogen peroxide-based system for converting a range of linear and cyclic olefins to epoxides with high selectivity and high atom economy [Science, 300,964 (2003)}. It's an advance over earlier epoxidations with expensive peroxides and peracids or with environmentally polluting chlorine. And a strategy to prepare molecular crystals with perfectly predictable architecture—by carrying out reactions on molecular crystals with porous interiors containing reagent-accessible reactive sites —was demonstrated by a group led by C & E N / D E C E M B E R 2 2 . 2003
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COVER STORY positives when screening such compounds, sites with nonspecific radical damage, as and Shoichet's group determined a mo had been thought. lecular mechanism for aggregation-in In a finding with possible implications duced inhibition [J. Med. Chem., 46,3448 for antibiotic resistance,Jon S. Thorson of and 4265 (2003)}. Both findings could aid the University ofWisconsin, Madison, and drug discovery coworkers discovered that the bacterium In combinatorial chemistry there's been that biosynthesizes the antibiotic calian increasing focus on synthesis of naturalcheamicin has a bodyguard protein that product-like compound collections (li sacrifices itself (via calicheamicin-induced braries) as potential founts of bioactive cleavage) to disable free calicheamicin that agents. Stuart L. Schreiber of Harvard Uni might damage the bacterium [Science, 301, versity and coworkers devised a strategy 1537(2003)}. for making natural-product-like libraries In research on protein-folding diseases, of unprecedented diversity [Science, 302, Surachai Supattapone and coworkers at 613 (2003)}· They use core structures ("la Dartmouth Medical School, Hanover, tent intermediates") that react with pe N.H., found that RNAhelps convert nor ripheral groups ("skeletal information ele mal endogenous "cellular prion protein" to ments") to generate compounds having all the infectious form that causes transmis possible combinations of a set ofboth core sible spongiform encephalopathies [Naskeletal frames and peripheral groups. ture, 425,717 (2003)}. The cellular factors In pharmaceutical chemistry, Immuinvolved were previously unknown. cillin-H (BCX-1777) became "the first drug Small-molecule compounds that inhib designed from an experimentally deter it protein misfolding related to neurode mined transition state to make it to the generative amyloidoses were identified by clinic," according to Vern L. Schramm of Jeffery W Kelly and coworkers at Scripps Albert Einstein College of Medicine, Research Institute [Science, 2 9 9 , 713 Bronx, Ν. Υ, who led a group that created (2003)}. the leukemia agent. Carl Τ Wild of Panacos Pharmaceuti Synthetic erythropoiesis protein (SEP, cals, Gaithersburg, Md., and coworkers shown)—created by total synthesis (red discovered PA-457, the first clinical de velopment candidate that targets H I V as sembly and maturation [Proc. Natl Acad. Set. USA, 100,13555 (2003)}. It could be come the first in a new class of AIDS drugs: maturation inhibitors. Richard A. Lerner and Paul Wentworth a: Jr. of Scripps and coworkers found that ozone is generated in arteriosclerotic plaques and may contribute to arterial dis ease via oxidation of cholesterol, low-den sity lipoproteins, and lipids found in such plaques [Science, 302,1053 (2003)}. The findings add ozonation to several other and green) and modified with a polymer proposed mechanisms for how plaque (blue)—could turn out to be the first com components become oxidized and cause pletely synthetic protein-based compound disease. MEDCHEM. Medicinal and combinatorial to become a commercial pharmaceutical [Science, 299, 884 (2003)}. Designed and chemistry has increasingly become a main synthesized by Gerd G Kochendoeifer of stay of chemical research, accounting in BIOSCIENCE. Capping more than a Gryphon Therapeutics, South San Fran part for the growing evolution of chem decade of international effort, the goals of cisco, and coworkers, SEP has longer last istry departments into departments of the Human Genome Project were com ing activity and is more potent in an ani chemistry and biology pleted successfully this year, two years mal model than is the anemia drug ahead of schedule. The "finished" genome One significant finding in 2002 was a re erythropoietin, which has a comparable sequence covered 99% of the genome and port by Brian K. Shoichet of Northwest backbone. closed 995% of the gaps in the rough draft ern University and coworkers that the po announced about two years earlier. tency of some inhibitory compounds Among chemistry-related studies on depends on their tendency to form aggre A new field called "ionomics"—the infectious diseases this year, the mecha gates —and not simply on the affinity with study of how genes regulate levels of sin nism of action of the antimalarial agent which they bind to their targets, as had a r t e m i s i n i n was revised by Sanjeev gle-element ions in cells —was conceived by generally been believed [J. Med. Chem., 45, Krishna of St. George's Hospital Med David E. Salt of Purdue University and 1712 (2002)}. This year, Chun-wa Chung coworkers [Nat. Biotechnol, 21, 1215 ical School, London, and coworkers [Na of GlaxoSmithKline, Stevenage, England, (2003)}. Mapping ion-regulating genes ture, 4 2 4 , 957 (2003)}. They found that and coworkers showed that detergents, could aid phytoremediation of pollutant the drug targets a calcium-pumping en which break up aggregates, can reduce false trace elements and lead to the engineerzyme, instead of attacking malarial para James D. Wuest of the University of Mon treal [Angew. Chern. Int. Ed., 4 2 , 5303 (2003)}. In organic catalysis, the first metal complexes that catalyze transamidation (amide-exchange reactions) efficiently un der moderate conditions were identified by Shannon S. Stahl, Samuel H. Gellman, and coworkers at the University of Wis consin, Madison \J. Am. Chem. Soc, 125, 3422 (2003)}. These complexes could ex pand the range of synthetically accessible amide-based compounds. R. Morris Bullock and Vladimir K. Dioumaev of Brookhaven National Labo ratory discovered an organometallic tung sten complex that precipitates at the end of a ketone hydrosilylation reaction—pro viding a new way to separate catalyst from product [Nature, 424,530 (2003)}. In carbohydrate chemistry this year, the first enzymatic method for the synthesis of sulfur-linked oligosaccharides—an ap proach that could be useful for construct ing thioglycosylated proteins—was de veloped by Stephen G Withers and coworkers at the University of British Co lumbia, Vancouver [Angew. Chem. Int. Ed, 42,352(2003)}. A novel way to identify proteins derivatized with O-linked N-acetylglucosamine (O-GlcNAc) or O-linked iV-acetylgalactosamine groups was devised by Carolyn R. Bertozzi of the University of California, Berkeley, and coworkers [Proc. Natl Acad. Set USA, 100,9116 (2003);Proc.Natl.Acad. Set. USA, published online Dec. 1, http://wwwpnas.org/cgi/content/abstract/ 2335201100vl}.The m e t h o d - i n which azides are used as handles for introduc ing detectable probes selectively into either type of glycosylated p r o t e i n could prove useful for high-throughput proteomics.
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C & E N / D E C E M B E R 2 2 . 2003
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ing of crop plants with enhanced nutritional value. In a study that could promote effi ciencies inpaper production, Vincent L. Chiang of Michi gan Technological University, Houghton, and coworkers used agene-transfer technique to create
ico, and coworkers reported hav ing used X-ray crystallography at very low temperatures to trap a high-energy oxyphosphorane intermediate in the active site of an en zyme that catalyzes phosphoryl transfer [Science, 299, 2067 (2003)}. The work appeared to re solve the
but mammals are unable to biosynthesize it, qualifying it as a vitamin.
STRUCTURE. In structural biochemistry in late 2002, Lucio Frydman and cowork ers at Weizmann Institute of Science, Rehovot, Israel, developed ultrafast multidi mensional nuclear magnetic resonance (NMR) spectroscopy, which shortens by orders of magnitude the time required to obtain 2-D and 3-D NMR spectra [Proc. Natl. Acad. Set. USA, 99,15858 (2002)}. The technique could speed studies of chemical structure and dynamics. And this trees that year a technique called G-matrix Fourier contain about transform NMR was devised by Thomas UP IN THE AIR Does halfthe usual amount Szyperski and postdoc Seho Kim of the ^ J t ^ this trigonal bipyramidal of lignin, which must State University of New^brk, Buffalo, al oxyphosphorane structure be chemically removed to so for the purpose of speeding multidi obtained by Allen, Dunaway-Mariano, make paper, and up to 30% mensional NMR [J. Am. Chem. Soc, 125, more cellulose [Proc. Natl. Acad. Set. USA,and coworkers represent an enzyme 1385(2003)}. caught in the act of phosphoryl 100,4939(2003)]. Using a 2-D NMR correlation ap An analytical technique for detecting transfer? The issue is in dispute. proach, the first high-resolution NMR DNAat femtomole levels without any need (Phosphorus = purple, oxygen = red, spectra ofdisordered solids—such as glass forprior DNAamplificationwas developed and carbon = yellow.) es, polymers, and biomaterials— were ob by M. Reza Ghadiri and coworkers at tained by Lyndon Emsley of Ecole Nor Scripps [J.Am. Chem. Soc, 125,344 (2003)}. question of how the enzyme performs this male Supérieure, Lyon, France; Alexander In the technique, complementary base physiologically important reaction. Howev Pines at the University of California, Berkepairing activates an enzyme that generates er, some believe Allen, Dunaway-Mariano, ley; and coworkers [jf.Am. Chem. Soc, 125, an optical signal. Potential applications in and coworkers may have trappedMgF3~ in 4376(2003)}. clude point-of-care diagnosis of diseases stead ofoxyphosphorane [Science, 301,1184 Using X-ray crystallography and kinetcaused by DNA defects or infectious (2003)}, and the issue remains undecided. ics, Dan S. Tawfik of Weizmann Institute agents. Andreas Pluckthun of the University of Science and coworkers found that a sinResearch on RNA interference of Zurich, G. Michael Blackburn of the gle antibody can take on two different con(RNAi)—a technique in which short RNA University of Sheffield, England, and formations, enabling it to bind two unrestrands are used to shut down gene ex coworkers devised an improved way to lated antigens [Science, 299,1362 (2003)}. pression selectively—has been experienc obtain highly efficient catalytic anti Agroup led by Daniel E. KoshlandJr. of ing explosive growth. Among other appli bodies [Nat. Biotechnol, 21,679 (2003)}. the University of California, Berkeley, decations, the technique provides a way to The technique combines turnover-based termined the first structures that show rapidly assess the consequences of gene chemical selection from a synthetic an drugs complexed with a bacterial mulsuppression in living animals, as a New tibody library with directed in vitro pro tidrug-transporter protein and proposed 'York City-based group showed this year tein evolution. [Nat. Struct. Biol., 10,91 (2003)}. Richard R. Schrock and Dmitry V YmResearchers of an enzymological per dulov of Massachusetts Institute of Tech suasion catalyzed a number of impressive nology developed "the most mechanisti advances in 2003. In a study to determine cally well-defined system that reduces N 2 how an enzyme with only a single active to NH 3 under modest temperature and site catalyzes a multistep DNA-repair pressure in a catalytic fashion,,, accord process, Gregory L. Verdine and cowork ing to a published comment on the work. ers at Harvard University revealed what They used a molybdenum aryltriamiappeared to be the first reported exam doamine complex to mimic the natural ple of product-assisted enzymatic catal process by which nitrogen-fixing enzymes ysis: a multistep process in which the produce NH 3 from N 2 [Science, 301, 76 product of an enzymatic reaction is used (2003)}. by the same enzyme to catalyze subse In a nutrition-relatedfindingthis year, quent steps [Nat. Struct. Biol, 10, 204 Tadafumi Kato's group at the RIKEN (2003)}. Substrate-assisted enzymatic Laboratory for Molecular Dynamics of catalysis had been observed previously, Mental Disorders, Saitama, Japan, dis but not the corresponding product-as covered that pyrroloquinoline quinone is ELEVATOR Koshland and coworkers sisted process. a new member of the family of Β vitamins obtained the first structures of drugs Karen Allen of Boston University [Nature, 422, 832 (2003)}. The com complexed with a bacterial multidrugSchool of Medicine, Debra Dunaway- pound is required for proper functioning transporter protein and proposed an Mariano of the University of New Mex of an enzyme that breaks down lysine, "elevator" mechanism. HTTP://WWW.CEN-ONLINE.ORG
C&EN
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COVER STORY an "elevator" mechanism of action [Science, 300,976(2003)}. A structural and mechanistic study of a voltage-dependent potassium ion channel by Roderick MacKinnon of Rockefeller University, New Ifork City, challenged a long-standing view about the mechanism by which this type of channel opens and closes in response to charge-distribution changes [Nature, 423, 33 and 42 (2003)}. MacKinnon shared the 2003 Nobel Prize in Chem istry with Peter Agre ofJohns Hopkins
Tel Aviv University and coworkers) and the Schultz of Scripps and coworkers [J.Am. reaction center/light-harvesting 1 complex Chem. Soc, 125,935 (2003)}. The modified of purple bacteria (by Neil W. Isaacs, bacteria synthesize proteins using a 21st Richard J. Cogdell, and coworkers at the amino acid,/>-ammophenylalanine, in ad University of Glasgow) revealed previous dition to the 20 that are common to all ly unknown details about photosynthetic other life forms. And thefirstmethod for systems [Nature, 426,630 (2003); Science, adding nonnatural amino acids to the ge netic code of aeukaryotic organism (yeast) 302,1969(2003)}. was devised by the same group and demon BIOENGINEERING. Sometimes, chemists strated by expressing proteins with 21 just won't let well enough alone—especially amino acids each, instead of the usual 20 when they think they can improve on na [Science, 301, 964 (2003)}. "We have ef ture. For example, Homme W. Hellinga fectively removed a billion-year constraint on our ability to manipulate the structure and function of proteins," Schultz said. After long-standing efforts by several groups, Tillman U. Gerngross of Dart mouth College and coworkers there and at GlycoFi Inc., Lebanon, N.H., geneti cally engineered yeast to produce proteins with glycosylation patterns similar to those in human proteins [Science, 301, 1244 (2003)}. The technique could lead to the production of novel therapeutics. In work with potential implications for DNA sensing and genetic tissue typing, Eric T. Kool and coworkers at Stanford University created an alternative genetic system based on DNA bases of expanded size [Science, 302,868 (2003)}. TRANSPORTERS Kaback, Iwata, and coworkers determined the structure of In the area oftissue engineering, the use LacY (left), and Wang's group obtained that of GlpT. ofbiodegradable polymer scaffolds to grow 3-D tissues from embryonic stem cells was University School of Medicine for re and colleagues at Duke University used demonstrated by Robert S. Langer ofMIT search on cell membrane channels. computational chemistry to redesign pro and coworkers [Proc. Natl. Acad. Sci. USA, Two groups obtained high-resolution teins to perform newnonnatural functions 100,12741(2003)}. structures of previously elusive members [Nature, 423,185 (2003)}. When the pro A collaborative French team sponsored of a family of membrane transporter pro teins were synthesized, they indeed worked by Aventis produced hydrocortisone bioteins [Science, 301, 610 and 616 (2003)}. as planned. synthetically in recombinant yeast from The structure ofLacY was solved by a team David Baker of the University ofWash- simple carbon compounds. Hydrocorti led by H. Ronald Kaback of the Universi ington, Seattle, and coworkers conceived sone, an anti-inflammatory steroid and key ty of California, Los Angeles, and So Iwa a large protein with a previously unknown synthetic intermediate, has been made in ta of Imperial College, London. And Da- shape, designed it computationally, syn dustrially using multistep chemistry and Neng Wang and coworkers at New %rk thesized it, determined its structure, and microbial bioconversion [Nat. BiotechnoL, University School of Medicine obtained found it to be an extremely close match 21,143(2003)}. the structure of GlpT. with the original conception [Science, 302, Another French group—Bilal Camara of Université Louis Pasteur, Strasbourg, Three independent teams determined 1364(2003)}. the unusual structure of the antibacterial Thefirstmicroorganisms that produce and coworkers—discovered the mechapeptide microcinJ25, one of the few a nonnatural amino acid and incorporate nism of biosynthesis of the commercially known natural molecules that block bac it into proteins were created by Peter G. important plant pigment bixin and planned to use the pathway to make bixin-producterial RNApolymerase [J.Am. Chem. Soc, ing tomatoes [Science, 300,2089 (2003)}. 125,12382,12464, and 12475 (2003)}.The studies were carried out by Gaetano Τ CLOSE MATCH Baker and Montelione of Rutgers University's Cen coworkers found that the crystal SENSORS & ANALYSIS. In the ter for Advanced Biotechnology & Medi structure (red) of a syn analytical realm this year, a cine and Richard H. Ebright of Howard thesized protein with a method for optical detection Hughes Medical Institute and the Waks- new "fold" was a of the activities of single man Institute at Rutgers; DavidJ. Craik at remarkably good molecules, even when the University of Queensland, Brisbane, match with the present at relatively high Australia; Seth A. Darst ofRockefeller Uni computationally concentrations, was versity and coworkers. designed model devised by Watt W. Webb and Harold G. Earlier this month, crystal structures of (blue) on which it plant photosystem I (by Nathan Nelson of was based. Craighead of Cornell SCIÊMCÉ
"\J
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COVER STORY technique makes it possible to detection was developed by J. Michael separate and analyze reaction Ramsey and coworkers at Oak Ridge Na intermediates and other tran tional Laboratory [Anal Chem., 75,5646 (2003)}. The apparatus makes it possible sient chemical species. Metal film A sensitive and selective to analyze single cells at rates of seven to \ colorimetric sensor for lead 12 cells per minute—more than 100 times developed by Yi Lu and a faster than the standard CE approach. Po coworker at the University tential applications include clinical diag of Illinois, Urbana-Cham- nosis and fundamental studies on cell-topaign, could lead to a long- cell heterogeneity sought simple and inexpen sive test kit for leaded paint INORGANIC CHEMISTRY. Novel struc \J.Am. Chem. Soc, 125,6642 tures continue to be a mainstay of inor (2003)}. The sensor—based ganic chemistry research. For example, the on gold nanoparticles and a first thermally stable, crys selective DNAzyme—may talline trisilaallene SiMe3 Collected fluorescence also prove useful for measur derivative (shown) | \^-—SiMe3 SINGLE-MOLECULE DETECTOR Webb, ing other metals, nonmetals, containing a for- M e 3 s , -y^ S j Craigheadp and coworkers developed this and compounds. mally sp-hybrid- Me3Si ^ "zero-mode waveguide" technique for £' The first electrochemical ized silicon atom β3 detecting single-molecule phenomena. . "\ s} DNAanalysis technique that's was synthesized by Me Sl 3 " ~ | ^_. S i M e 3 sensitive, specific, reagentless, chemistryprofesand reusable was developed by sor Mitsuo Kira SiMeo University and coworkers [Science, 299, Chunhai Fan, Kevin W Plaxco, and Alan and coworkers at Tohoku 682 (2003)}. Their "zero-mode wave J. Heeger of the University of California, University, Sendai [Nature, 421, 725 guides"—holes in a metal film that are Santa Barbara [Proc. Natl. Acad. Sci USA, (2003)}. The Si=Si=Si skeleton is bent (with a bond angle of about 136°) and re 100, 9134 (2003)}. It could provide smaller than the wavelength oflight—cre markably fluxional, in contrast to the rigid ate detection volumes as small as the basis for a portable, linear framework of carbon aliènes. Such trisilaallene derivatives could be useful as synthetic reagents and building blocks for functional materials. A novel metal dinitrogen complex, ^ M e ^ U i N ^ , is "the first monometal10 zepto- JIFFY TUBE lic f element complex of N 2 of any kind," liters(lzL=10-21L), Hourglass-shaped capillary made according to William J. Evans and it possible for Shear and coworkers to : the smallest ever reported. coworkers at the University of CaliforIn another development of miniature achieve microsecond electrophoretic nia, Irvine [J.Am. Chem. Soc, 125,14264 : proportions, Thomas G. Thundat and Lai separations. (2003)}. The work could lead to insights ! A. Pinnaduwage of Oak Ridge National | Laboratory and the University of Ten continuous analyzer for medical and mili into f element coordination chemistry and nitrogen fixation. nessee created a highly miniaturizable de tary applications. Alexander I. Boldyrev ofUtah State Univice for detecting plastic explosives with a Chad A. Mirkin of Northwestern Uni I sensitivity higher than that of any existing versity and coworkers devised an ultra versity, Lai-Sheng Wang of Washington : technology [Appl. Phys. Lett, 83, 1471 sensitive protein detection method that State University and Pacific Northwest (2003)}. Large and expensive instruments may be useful in cancer diagnosis [Science, National Lab, and coworkers reported a like ion mobility spectrometers are cur 301,1884 (2003)}. The target protein is Li3Al4" anion they prepared to be the first rently used to detect plastic explosives in captured by antibodies, separated mag inorganic antiaromatic species ever idenairports and other locations. netically, and identified by encoded DNA, tified [Science, 300,622 (2003)}. However, some others believe that overall the Two groups—Bernhard Lendl at Vi which provides an amplifying effect. enna University of Technology, in Aus Combining fluorescent monomers and species is aromatic, not antiaromatic [J. tria, and coworkers and Staffan Nilsson polymers that undergo temperature-in Am. Chem. Soc, 125,13930 (2003)}, and at Lund University, in Sweden, and duced phase transitions in water produces the issue is currently unresolved. coworkers—developed the first surface- "by far the most sensitive fluorescent mo enhanced Raman spectroscopy tech lecular thermometers known," according ENVIRONMENT. Among key developniques for measuring vibrational spectra to Seiichi Uchiyama and Kaoru Iwai of ments in environmental chemistry this of samples in tiny airborne droplets Nara Women's University, in Japan, and year, a thermophilic catalase purified and [Anal. Chem., 75,2166 and 2177 (2003)}. coworkers [Anal Chem., 75,5926 (2003)}. characterized byVicki S. Thompson ofthe Jason B. Shear's group at the University The devices can potentially be used as bi Department of Energy's Idaho National of Texas, Austin, achieved capillary elec ological nanosensors or as monitors of mi- Engineering & Environmental Laboratotrophoresis separations in less than 10 mi croreactor temperature. ry, Idaho Falls, and coworkers could help croseconds—about 100-fold faster than In microfluidics, a device that combines make industrial bleaching processes more any previous CE procedure [Proc. Natl cell handling, rapid-cell lysis, electro bemga[Biotechnol.Prog., 19,1292 (2003)}. Acad. Sci. USA, 100, 3853 (2003)}. The phoretic separation, and fluorescence The enzyme converts the environmentalHTTP://www.CEN-ONLINE.ORG
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COVER STORY ly safe bleaching agent hydrogen peroxide ence, 300,1127 (2003)}. It's a step toward to water and oxygen under the high-tem the practical use of hydrogen as a fuel. perature and high-pH conditions of in Among other materials breakthroughs dustrial processes —which wasn't possible in 2003, a procedure for spinning com previously— so process water can be reused posite carbon nanotube fibers that are or returned to the environment. tougher than spider silk and any other nat Chlorinated hydrocarbons are com ural or synthetic organic fiber reported monly destroyed by incineration above previously was devised by Ray H. Baugh1,300 °C, but a lanthanide oxide-based man of the University oflexas, Dallas, and catalytic system developed by chemistry coworkers [Nature, 423, 703 professor Bert M. Weckhuysen and co (2003)}. The newfibersmaybe workers at the University of Utrecht, in useful for advanced supercathe Netherlands, destroys them at much pacitors and textiles. lower temperatures and could thus save Since thefirstreport in 1986 energy and money [Angew. Chem. Int. Ed.,of high-temperature super 41,4730(2002)}. conductivity in layered copper Plants are usually considered a sink for oxides, researchers have nitrogen oxides (NOx), not a source. But searched without success for Pertti Hari of the University of Helsinki similar behavior in other layand coworkers found that exposure to ul traviolet rays causes pine trees to emit LAYERED LOOKTakada NOx—suggesting that forest emissions of and coworkers found that these smog-forming compounds could be this cobalt oxide-based significant [Nature, 422,134 (2003)}. layered complex exhibits MATERIALS. Materials science advances can also sometimes be used to help solve environmental problems. An example is the class of "green" zeolites developed this year. Ralph T. "Yang and coworkers at the University of Michigan, Ann Arbor, dis covered zeolites that adsorb aromatic sul fur compounds from commercial fuels at ambient temperature and pressure [Science, 301, 79 (2003)}. The zeoliteswhose selectivity and capacity for sul fur are at least 40 times higher than those reported previously—could help refineries meet strict air-quality regulations. Mark E. Davis and colleagues at Caltech and Chevron recendy created zeolitetemplating structure-directing agents (SDAs) that can be disassembled after ze olite synthesis at relatively low tempera tures, allowing the molecular fragments to be removed, recovered, and reused [Na ture, 425,385 (2003)}. The work advances green chemistry because SDAs usually have had to be burned off at high temper atures, which is wasteful, expensive, and sometimes detrimental to the zeolites themselves. In another materials chemistry ad vance with potential environmental ap plications, Omar M. Yaghi of the Uni versity of Michigan, Ann Arbor, and coworkers designed and constructed met al-organic framework crystals with an ex tended porous structure that can adsorb up to 2% by weight of hydrogen at room temperature and 10 atm of pressure and up to 4.5% at lower temperatures [Sci 66
C & E N / D E C E M B E R 2 2 , 2003
superconductivity, just like the layered copper oxides that created a sensation when they were discovered in 1986.
ered transition-metal oxides. In 2003, KazunoriTakada ofNational Institute for Materials Science, Tsukuba, Japan, and coworkers found a cobalt oxide that be comes superconducting at about 5 Κ [Nature,
[Science, 300,2072 (2003)}. Aida's group also helped integrate biomolecular motion into materials science by demonstrating that large barrel-shaped chaperonin pro teins can entrap and stabilize a quantum dot (semiconductor nanoparticle) as a guest and release it in response to adeno sine triphosphate binding—the usual trig ger for chaperonins to release a refolded protein [Nature, 423, 628 (2003)}. Liquid-crystal compounds that are Janus-like (with two chemically different halves) and self-organize into materi als with desirable chemical functionality and physical properties at nano- and mesoscopic length scales were de signed, synthesized, and char acterized by Isabel M. Saez and John W. Goodby of the Uni versity of Hull, in England [Chem. Commun., 2003,1726}. A beautiful purple glass, in which nanoscale-size magnetic particles of a Co(II)/Fe(III) Prussian blue complex form spontaneously in a single-pot sol-gel reac tion, was developed by Albert E. Stiegman of Florida State University and coworkers [Angew. Chem. Int. Ed., 42,2741 (2003)}. The material is transparent and super paramagnetic—each nanoparticle be haves like an independent magnetic domain—and it exhibits tunable
JANUS Goodby and Saez designed the "two-faced" • v X r- dendritic compounds at left, ^ & ^ n > C o - o - < r r ^ which have chemically 422,53(2003)}. different components (yellow Takuzo Aida of the Uni vêrsity of Tokyo, Takanori Fukushima of and blue) that form liquid crystals. Japan Science & Technology Agency, and Below, X-ray diffraction "pole figures" coworkers discovered that carbon nano- of two copper oxide films tubes and room-temperature ionic liquids electrodeposited on a gold substrate can be blended to form gels that may be by Switzer and coworkers are used to make novel electronic devices, nonsuperimposable mirror images, coating materials, and antistatic materials showing that the films are chiral.
HTTP://WWW.CEN-ONLINE.ORG
photomagnetism, suggesting magnetic switch applications. Gerard C. L. Wong and coworkers at the University of Illinois, Urbana-Champaign, developed a biomineralization procedure in which molecular details of biological molecules are replicated on inorganic crystals by electrostatically guiding crystallization at the nanoscale [J.Am. Chem. Soc, 125, 11786 (2003)}. Such custom-designed crystals could have useful electronic, magnetic, and optical properties. Anew way to create solid chiral surfaces having catalytic properties may make it easier to synthesize or sense chiral molecules. A team led by Jay A. Switzer of the University of Missouri, Rolla, discovered how to electrochemically deposit a copper oxide film with either right- or lefthanded chirality onto an achiral gold surface [Nature, 4 2 5 , 4 9 0 (2003)]. YbGaGe, the first electrically conductive compound that maintains its roomtemperature volume when heated, was prepared and characterized by Mercouri G. Kanatzidis and coworkers at Michigan State University East Lansing [Nature, 425, 702 (2003)}· Potential applications of such electrically conducting zero-thermal-expansion materials include multilayered printed circuits. SUPRAMOLECULAR CHEMISTRY. Some
of the super supramolecular advances this year involved ion recognition, fullerenes, molecular motors, and dendrimers. The first single molecule to completely encapsulate an ion pair in polar media was synthesized byJerry L. Atwood and a
TRAPPED Atwood and coworkers synthesized this ion-pair trap—the first single molecule to completely encapsulate an ion pair in polar media. HTTP://WWW.CEN-ONLINE.ORG
The first single-trigger, multiple-release dendrimers were reported this year [Angew. Chem. Int. Ed., 42,4490 and 4494 (2003)}. F. M. H. (Vincent) de Groot of Syntarga B.V, Nijmegen, the Netherlands, and colleagues call their structures "cascade-release dendrimers," and Doron Shabat and coworkers at Tel Aviv University call theirs "self-immolative dendrimers." A similar "dendritic amplification" technique was reported subsequently by Dominic V McGrath of the University of Arizona, Tucson, and coworkers [J.Am. Chem. Soc, published online Nov. 26, http:// dx.doi.org/10.1021/ja0386694}.Potential applications include drug delivery or chemical amplifiers. NAN0TECH & MOLECULAR ELECTRON-
HYDROGEN CAPSULE Komatsu and coworkers synthesized this opencage fullerene, which can be filled with hydrogen (white spheres). coworker at the University of Missouri, Columbia [Chem. Commun., 2 0 0 3 , 940}. Anion-sensing applications are possible because the cation complex forms first and then attracts the anion selectively EXPLODING DENDRIMER Single activation of dendrimers designed independently by groups led by de Groot and Shabat causes spontaneous release of multiple end groups. T h e first open-cage fullerene derivative with an orifice large enough to allow a hydrogen molecule to be inserted into the cage in 100% yield was prepared by Koichi K o m a t s u and coworkers at Kyoto University, Japan [J. Am. Chem. Soc, 125,7152 (2003)}. Hydrogen storage applications are possible. A supramolecular motor with components that rotate in only one direction was developed by David A. Leigh of the University of Edinburgh, in Scotland, and coworkers [Nature, 424,174 (2003)}. It's the first molecular motor to be made of components that do not share covalent bonds.
ICS. Although the question of whether nanorobots can exist remains unresolved, progress nevertheless continues apace on a range of nanoscale techniques and molecular electronic devices. The first nanoscale light source based on a single carbon nanotube (acting as a field-effect transistor) was demonstrated by Phaedon Avouris, James A. Misewich, Richard Martel, and coworkers at IBM'sT J. Watson Research Center, Yorktown Heights, N.Y. [Science, 300, 783 (2003)}. An IBM group including Avouris, Martel, and Marcus Freitag also generated an electrical current in a single carbon nanotube by shining light on it [Nano Lett., 3,1067 (2003)}. Both studies have implications for miniature photonic and optoelectronic devices. A technique for changing nanotube electrical properties was devised by Robert G Haddon and coworkers at the University of California, Riverside. They showed that functionalizing conductive metallic nanotubes with dichlorocarbene caused the nanotubes to take on semiconducting properties [Science, 301,1501 (2003)}. Michael S. Strano of the University of Illinois, Urbana-Champaign, James M. Tour and Richard E. Smalley of Rice University, and coworkers found this year that functionalizing nanotubes with diazonium reagents differentiates metalC & E N / D E C E M B E R 2 2 . 2003
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COVER STORY tory [Nature, 4 2 4 , 4 0 8 (2003)1. Four-armed CdTe nanocrystals made by .Électrons A. Paul Alivisatos and coworkers at the University of California, Berkeley, and Lawrence BerkeNanotube ley National Laboratory [Nat.Mater, 2,382(2003)1 Silicon oxide were described as "one of the best controlled nanocrystal systems with Gate electrode complex shapes." T h e nanocrystals could find use in solar cells or as TOTALLY TUBULAR By injecting charge carriers polymer additives. (holes and electrons) at opposite ends of a carbon nanotube, Avouris, Misewich, Martel, and coworkers Molecular electronics display-related developat IBM produced polarized infrared light. ments this year included a polymer-based electroluminescent delie and semiconducting single-walled carvice that can be switched between glowing bon nanotubes and makes it possible to red or green by reversing the direction of separate and manipulate them, based on differences in electronic structure [Science, current flow It was produced by Luisa De Cola at the University of Amsterdam, 301,1519 (2003)}. And Ming Zheng of Klemens Brunner at Philips Research LabDuPont Central Research & Developoratories, Eindhoven, the Netherlands, ment, Wilmington, Del., and coworkers and coworkers [Nature, 421, 54 (2003)1. showed that certain sequences of D N A The device could simplify the fabrication can wrap helically around single-walled carand increase the brightness of displays, bon nanotubes and also permit them to be light sources, and color switches. separated, based on optical features [SciA new solution-processing method can ence, 302,1545 (2003)1 be used to pattern red, green, and blue elecVictor I. Klimov and coworkers at Los troluminescent polymers with resolution Alamos National Laboratory showed that that exceeds what's required for flat-screen, amplified spontaneous emission—an imfull-color organic light-emitting diode disportant step toward tunable IR lasers— plays. Formerly, the resolution of wetcan be achieved in the near-IR region using nanocrystals oflead salts [J. Phys. Chem. chemical patterning processes for electroluminescent polymers wasn't high B, published online Nov. 21, http://dx. enough to create such displays. The new doi.org/10.1021/jp0311660]. method was developed by Klaus Meerholz In a moving development, the first at the University of Munich (now at the nanometer-sized, electriUniversity of Cologne); Heinrich Becker of cally driven synthetic Covion Organic Semiconductors, Frankmotor— a gold rotor and a multiwalled carbon n a n o t u b e NAN0TETRAP0D These CdTe axis on a silicon nanocrystals were created by Alivisatos chip—was built by and coworkers. Alex Z e t t l and coworkers at the Unifurt; Oskar Nuyken at the Technical versity of California, University ofMunich; and coworkBerkeley, and Lawers [Nature, 421,829 (2003)]. rence Berkeley NaA novel technique for aligning tional Laboraliquid crystals—developed by RoelandJ. M. Nolte of the University of Nijmegen, the Netherlands, and coworkers—eliminates the current need for clean-room conditions in liquid-crystal display manufacture [Angew. Chem. Int. Ed., 4 2 , 1812 (2003)1. Chemistry professor C & E N / D E C E M B E R 2 2 , 2003
James R. Heath of California Institute of Technology and coworkers devised a method for producing ultrahigh-density arrays of aligned nanowires and nanowire circuits [Science, 300,112 (2003)1. And a Technion-Israel Institute of Technology team led by Erez Braun and Kinneret Keren created a field-effect transistor by binding a single-wall carbon nanotube to a D N A strand and fabricating gold leads to the nanotube [Science, 3 0 2 , 1380 (2003)1- Techniques like this "will pave the way for integration of molecular components into useful microelectronics," a researcher commented. In addition, many research teams are working to develop soft, flexible electronic technologies based on conducting fibers or organic thin-film materials. In one such study, Xiangfeng Duan and coworkers at Nanosys, in Medford, Mass., and Palo Alto, Calif, devised a low-cost, low-temperature process for fabricating high-performance thin-film transistors on flexible substrates [Nature, 425,274 (2003)1- The technology takes "nanoelectronics in a new direction," Duan tells C&EN, "exploiting nanomaterials not for electronic miniaturization, but for better and cheaper electronics over large areas." POLYMER CHEMISTRY. Polymer science developments this year included advances in polymer synthesis, tailoring of polymer properties, and plastics processing. Guillermo C. Bazan of the University of California, Santa Barbara, and coworkers devised a three-component catalyst system to prepare branched polymers with structures that cannot be obtained with a single catalyst or catalyst pair [J.Am. Chem. Soc, 124,15280 (2002)1. The group's study was facilitated by a novel high-throughput screening technology developed by researchers at SymyxTechnologies and Dow Chemical who used the technology to rapidly discover hafnium-based complexes that catalyze olefin polymerization [J.Am. Chem. Soc, 125,4306 (2003)]. The SymyxDow team found that some of the complexes performed as well as or better than DoVs workhorse metallocene polyolefin catalyst system. In a potentially blessed development, H. YUdirim Erbil of Kocaeli University, in Turkey, A. Lèvent Demirel of Koç University, Istanbul, and coworkers devised a simple, inexpensive method for converting polypropylene into a coating whose surface strongly repels water, much like the leaves of the sacred lotus plant [Science, 299,1377 (2003)]. In the past, such efforts have generally involved expensive materiHTTP://WWW.CEN-ONLINE.ORG
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als and complex, time-consuming process es. The coatings could be useful in microfluidic devices and to protect outdoor surfaces from icing or fouling. A new high-pressure component-mix ing technique developed by Anne M. Mayes and coworkers at M I T makes it pos sible to mold plastics at room temperature [Nature, 426,424 (2003)]. It could lead to energy savings in industrial plastics pro cessing and promote plastics recycling. PHYSICAL & SURFACE CHEMISTRY. This was also a busy year for those who like to "get physical" and to focus on the surface of things. The speed of aqueous proton transfer from acid to base was measured and a de tailed mechanism proposed by Ehud Pines of Ben-Gurion University of the Negev, Is rael; Erik Τ J. Nibbering of Max Born In stitute for Nonlinear Optics & Short Pulse Spectroscopy, Berlin, Germany; and coworkers {Science, 301,349 (2003)].They found an extra stage of the mechanism that had never been observed previously Also awash with significance were find ings by Anne Willem Omta of the F O M Institute for Atomic & Molecular Physics, Amsterdam, the Netherlands, and cowork ers that ion solvation affects water's hy drogen-bonding network only in the sin gle layer of water molecules surrounding the ion [Science, 301,347 (2003)}. This con tradicts existing views that ions cause nonlocalized water-structure effects throughout an en tire solution. A truly momentous de velopment was the deter mination of the largest transient dipole moment ever measured—150 debyes (D), in a caroteneporphyrin-fullerene arti ficial photosynthetic system—by Sergei N . Smirnov of New Mexico State University; Devens Gust, Ana L. Moore, andThomas A. Moore of Arizona State University; and cowork ers [J.Phys. Chem.A, 107,7567 (2003)1. The previous record was 100-120 D.The study is of fundamental interest and could have implications for ultrafast switching. In surface science this year, a switchable surface created by MIT's Robert S. Langer and coworkers was hailed as "amaz ing" by one observer. The self-assembled alkanethiolate monolayer can be made to stand or collapse by applying an electrical potential to reversibly switch its confor mational state [Science, 299,371 (2003)}.
BEND OVER BACKWARD Langer's group created this controllably switchable selfassembled monolayer surface. Such surfaces might be useful for microfluidics, drug delivery, electro-optics, or offset printing. Little has been known about the atom ic-scale dynamics of defects on transitionmetal oxide crystal surfaces. But using time-lapse scanning tunneling microscopy, Flemming Besenbacher of the University of Aarhus, in Denmark, and coworkers showed this year that oxygen vacancies dif fuse across a surface along specific crystal directions; these findings * could aid the ability to * control the number and d distribution of oxygen « vacancies on such suri5 faces [Science, 299, 377 | (2003)}. A method to profile polarity changes across water-oil interfaces was developed by Robert A. Walker and William H.
>
Steel of the University MOLECULAR RULERS Walker and Steel developed surfactants (green oval linked to red circle) capable of profiling polarity changes across water-oil interfaces (surrounding molecules). of Maryland, College Park[Nature, 424, 2 9 6 (2003)}. It's based on "molecular rulers": surfactants that each contain a hydrophobic probe, a spacer, and an an ionic head group. The technique has im plications for phase-transfer catalysis, drug bioavailability, and other interfacial phenomena. • HTTP://WWW.CEN-ONLINE.ORG
