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COVER STORY INDIA ON THE RISE Approaching a year in office, the Indian prime minister promises less regulation of the country’s chemical makers. PAGE 10

QUOTE NEWS OF THE WEEK GOVERNMENT & POLICY OF THE WEEK 5 HARNESSING TRANSCRIPTION FACTORS 22 CONCENTRATES “If you are Smuggled into cells, they might be used 23 HIGH COURT TO RULE ON AIR POLLUTION following therapeutically, researchers say. Justices hear arguments on EPA’s regulations on science, it is 6 REFORMING THE LAW ON CHEMICALS mercury and other toxic air pollutants. like following Senate takes a giant stride to reform the Toxic 25 MICHAEL E. ROGERS your favorite Substances Control Act. C&EN talks with the recently retired National TV drama 6 CHORUS OF DUPONT CRITICS GROWS Institute of General Medical Sciences division because there Two of three shareholder advisory services back director. is always a new some change for firm’s board of directors. development.” 7 BOMBARDIER ’S TOXIC SPRAY SCIENCE & TECHNOLOGY MICHAEL E. X-ray imaging reveals new details of how critter’s 26 CONCENTRATES ROGERS; RECENTLY internal reactor whips up bursts of hot irritant. 28 FROM THE SCENES RETIRED DIRECTOR 7 ASIA-PACIFIC TRADE AGREEMENT 29 A FIGHT OVER SMELL OF THE DIVISION OF Fight over fast-track authority imperils deal. New research rebuts evidence for the vibrational PHARMACOLOGY, 8 NEURONS’ RISKY MOVES theory of olfaction. PHYSIOLOGY & BIOLOGICAL CHEMISTRY; DNA methylation by neurons may be a maneuver 30 HAPPY 25TH NATIONAL INSTITUTE tied to learning and memory, researchers say. BIRTHDAY, HUBBLE! ▶ OF GENERAL MEDICAL 8 ROADBLOCK FOR EPA HARDENS Groundbreaking space SCIENCES PAGE 25 Legislation would force regulators to release telescope has revealed confidential clinical health data. surprising stellar 23 9 GRAPHENE INK chemistry. Aerogels with graphene flakes can print three 32 SHIPWRECKED dimensionally for numerous applications, CHAMPAGNE developers say. ANALYZED 9 BASF CELEBRATES 150 YEARS Bubbly that’s 170 years Firm’s lavish party was dampened by a blunt old reveals 19th-century winemaking methods speech from German Chancellor Angela Merkel. and tastes.

BUSINESS THE DEPARTMENTS 16 CONCENTRATES 2 LETTERS 35 MEETINGS 18 FIGHTING HEPATITIS B 3 EDITOR’S PAGE 36 ACS CAREER TIPS Michael Sofia, inventor of a huge-selling 33 ACS COMMENT 36 CLASSIFIEDS hepatitis C drug, sets his sights on hepatitis B. 34 AWARDS 40 NEWSCRIPTS 20 WAFER-THIN ADVANTAGE Wacker Chemie hopes a granular polysilicon COVER: A BASF chemical plant in Mangalore, India. process can give the firm a competitive edge. BASF

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in regional events, or contributing to educational programs. If IT’S OFFICIAL: you would like to see the petition and support us with a signature, CANNABIS CHEMISTRY COMMITTEE please go to tinyurl.com/naonap7. Ezra M. Pryor AN EFFORT TO ESTABLISH a cannabis chemistry division at the Chair, Cannabis Chemistry Committee American Chemical Society has been under way since September Ontario, Calif. 2014 (C&EN, Nov. 10, 2014, page 4). Great strides were made at the ACS national meeting in Denver. The Cannabis Chemistry Committee was established as an official committee of the Small CASTING DOUBT ON SYRIA’S GUILT Chemical Businesses Division (SCHB). I was elected chair; addi- tional members will be found among many of the individuals who “WHEN CHEMICALS Became Weapons of War” claims that expressed strong interest in active membership. “hundreds of Syrian civilians [were] killed by their military’s use The greatest student interest (undergraduate and graduate) of sarin” (C&EN, Feb. 23, page 21). Not to put too fine a point on it, comes from schools in the Northwest and Southeast. These will but the attribution of responsibility for this atrocity has been far likely be the first locations for networking events that will bring from unanimous. The French government, former colonial ruler of students face-to-face with industry leaders, academic researchers, Syria, led the charge in accusing the Syrian government of having and like-minded peers. launched the attack. The petition for division formation received more than 300 sig- An article on the website truth-out.org, on April 29, 2014, sum- natures—50 signatures are needed. marizes evidence that casts doubt on this rush to judgment. The The committee will plan programming at upcoming meetings author writes that “the debate over the Aug. 21 attacks has focused and will hold networking events. At the 2016 spring ACS national primarily on a series of assertions about ‘smoking guns’ that al- meeting in San Diego, a full-day symposium cohosted by SCHB and legedly proved Syrian government guilt.” The article proceeds to the Agricultural & Food Chemistry Division will be organized. The quote evidence that the areas within a radius of 2 km from the im- first networking events will take place in June. pact sites were controlled by rebels. For those who were not able to meet us in Denver but would like Credible alternatives to C&EN’s version of events in Syria do to participate, please contact us at acscannabischemistry@gmail. exist. com. Member activities could include mentoring, participating Karl H. Hiller Spring Valley, N.Y.

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CEN.ACS.ORG 2 MAY 4, 2015 CHEMICAL & ENGINEERING NEWS 1155—16th St., N.W., Washington, DC 20036 FROM THE EDITOR (202) 872-4600 or (800) 227-5558 EDITOR-IN-CHIEF: Bibiana Campos Seijo MANAGING EDITOR, EDITORIAL: Amanda Yarnell MANAGING EDITOR, PRODUCTION: Rachel Sheremeta Pepling EDITOR-AT-LARGE: Rudy M. Baum SENIOR ADMINISTRATIVE OFFICER: Marvel A. Wills ‘Nothing Goes On Forever’ NEWS William G. Schulz, Editor BUSINESS THAT’S THE FIRST SENTENCE NEW YORK CITY: (212) 608-6306 Michael McCoy, of a great stone: that of August Kekulé’s cyclohexatri- Assistant Managing Editor, Rick Mullin (Senior Editor), Angewandte Chemie article by George M. ene representation of the structure of ben- Marc S. Reisch (Senior Correspondent), Alexander H. Tullo (Senior Correspondent), Rachel Eskenazi Whitesides in which he looks at the evolu- zene. Kekulé was a chemistry professor at (Administrative Assistant). CHICAGO: (917) 710-0924 Lisa M. Jarvis (Senior Correspondent). HONG KONG: tion of chemistry from World War II until Belgium’s University of Ghent when at the 852 9093 8445 Jean-François Tremblay (Senior Correspondent). HOUSTON: (281) 486-3900 Ann M. now (2015, DOI: 10.1002/anie.201410884 ). beginning of 1865 he revealed his molecular Thayer (Senior Correspondent). : 44 1494 564 The postwar years were very kind to vision of benzene in a short article present- 316 Alex Scott (Senior Editor). WASHINGTON: (434) 202-1986 Melody M. Bomgardner (Senior Editor) chemistry. Efforts to analyze and under- ed at a meeting of the Société Chimique de GOVERNMENT & POLICY stand complexity gave birth to academic Paris ( Bull. Soc. Chim. de Paris 1865, 3, 98) . Cheryl Hogue, Assistant Managing Editor Britt E. Erickson (Senior Editor), Steven K. Gibb chemistry, while society’s need for essen- The empirical formula for benzene had (Senior Editor), Glenn Hess (Senior Correspondent), Jeff Johnson (Contributing Editor), Jessica Morrison tial chemicals such as high-octane fuels or been known for some time, but its highly (Assistant Editor), Andrea L. Widener (Associate Editor) synthetic rubber created a vibrant chemical unsaturated structure was challenging to SCIENCE/TECHNOLOGY/EDUCATION industry. But of course, “nothing goes on determine. In the preceding years, other WASHINGTON: Lauren K. Wolf (Assistant Managing Editor), Celia Henry Arnaud (Senior Editor), Stuart A. Borman (Senior forever,” and by the time we get to the 1980s, scientists had suggested structures con- Correspondent), Andy Brunning (Contributing Editor), Matt Davenport (Associate Editor), Stephen K. Ritter (Senior Whitesides deems this prolific era “over.” taining multiple rings or double bonds, but Correspondent). BERLIN: 49 30 2123 3740 Sarah Everts He argues that the public perception of the evidence at the time was insufficient to (Senior Editor). BOSTON: (973) 922-0175 Bethany Halford (Senior Editor). CHICAGO: (847) 679-1156 Mitch Jacoby chemistry today remains “unarguably essen- pinpoint the correct structure. So chem- (Senior Correspondent). WEST COAST: (626) 765-6767 Michael Torrice (Deputy Assistant Managing Editor), (925) tial, but not exciting.” But he also points to ists of Kekulé’s day had to rely on evidence 226-8202 Jyllian Kemsley (Senior Editor), (206) 595-4788 Deirdre Lockwood (Contributing Editor), (510) 390-6180 opportunities. In fact, he goes on to describe from chemical reactions (wet chemistry) Elizabeth K. Wilson (Senior Editor) JOURNAL NEWS & COMMUNITY: many of these as “urgent necessities,” in- rather than using instrumental methods. (510) 768-7657 Corinna Wu (Senior Editor) cluding rational design of drugs, determin- Kekulé suggested that benzene con- ACS NEWS & SPECIAL FEATURES ing how the brain works, and more. White- tained a six-membered ring of carbon Sophie L. Rovner, Assistant Managing Editor Linda Wang (Senior Editor). DALLAS: sides offers chemistry as “the most plausible atoms with alternating single and double (972) 529-4351 Susan J. Ainsworth (Senior Editor) expertise” to resolve these challenges. bonds. But it wasn’t until 1929 that the EDITING & PRODUCTION Kimberly R. Bryson, Assistant Managing Editor But if there is little appreciation of a cyclic structure of benzene was finally con- Craig Bettenhausen (Associate Editor), Sophia L. Cai field, there is little public support for it firmed by crystallographic analysis. (Senior Editor), Mitch A. Garcia (Assistant Editor), Manny I. Fox Morone (Assistant Editor), and ultimately little money. I agree this is In any case, Kekulé’s idea of assigning Arlene Goldberg-Gist, Senior Editor Jeff A. Huber (Associate Editor), a serious and real risk: Little support will certain atoms to certain positions within Gail M. Mortenson (Senior Editor) influence the decisions made by govern- the molecule and connecting them using CREATIVE ments, whose preference in terms of areas what we now call bonds makes him the Robert Bryson, Creative Director Tchad K. Blair, Deputy Creative Director to invest in may fluctuate with public opin- founder of the theory of chemical struc- Robin L. Braverman (Senior Art Director), Ty A. Finocchiaro (Senior Web Associate), ion, which will of course directly affect the ture. He was hailed as one of the most Yang H. Ku (Senior Associate Designer), William A. Ludwig (Associate Designer) monies that go to funding bodies. prominent chemists in Europe at the time.

DIGITAL PRODUCTION Interestingly, Whitesides notes that oth- The new understanding of benzene, and Renee L. Zerby, Manager, Digital Production er scientific fields “manage to be exciting.” hence of aromaticity, was very important Luis A. Carrillo (Web Production Manager), Marielyn Cobero (Digital Production Associate), I spoke about this during the American for both pure and applied chemistry. To Joe Davis (Lead Digital Production Associate), Krystal King (Lead Digital Production Associate), Chemical Society Board of Directors open this day, aromaticity is a matter of discus- Shelly E. Savage (Senior Digital Production Associate), Cesar Sosa (Digital Production Associate) meeting at the recent ACS national meeting sion for the chemical science community in Denver. I argued that other sciences are as evidenced by the arguments expressed PRODUCTS MANAGER: Pamela Rigden Snead perceived as “sexier.” Physicists talk about in “Aromaticity for All,” a recent article SALES & MARKETING Stephanie Holland, Manager, Advertising Sales & Marketing the stars, the origin of life, black holes, and by C&EN Senior Correspondent Stephen Natalia Bokhari (Digital Advertising Associate), Kirsten Dobson (Marketing Coordinator), the Big Bang Theory; biologists talk about Ritter about how the concept should be in- Sondra Hadden (Senior Digital Marketing Specialist) Earth, oceans, and all living things includ- voked. You can follow and contribute to the ADVISORY BOARD ing cute furry that make people go debate at http:// cenm.ag/aromaticity . Gary D. Allred, Seth M. Cohen, Kendrew H. Colton, Cathleen Crudden, Michelle M. Francl, Paula T. Hammond, “ooooh.” But chemists talk about chemi- Matthew Hartings, Christopher Hill, Abraham M. Lenhoff, Scott P. Lockledge, Cheryl A. Martin, Peter Nagler, cals and man-made stuff, terms that often Michael O. Okoroafor, Dan Shine, Michael Sofia, Michael Strem, William Tolman, Jill Venton, Linette M. Watkins, carry negative connotations. So I’d agree Christopher Welch, Geofrey K. Wyatt, Vicki Wysocki that chemistry has a serious image problem Published by the AMERICAN CHEMICAL SOCIETY and advocate that individual chemists and Thomas M. Connelly Jr., Executive Director & CEO Brian D. Crawford, President, Publications Division organizations and societies like ACS need Kevin A. Davies, Vice President, Business Development & Publisher, C&EN to work together to turn that around. A. Maureen Rouhi, Director, Editorial & Business Development, C&EN Asia 150 YEARS OF BENZENE EDITORIAL BOARD: Stephanie L. Brock (Chair); ACS Board of Directors Chair: Pat N. Confalone; ACS Besides BASF’s 150th anniversary (see President: Diane Grob Schmidt; Cynthia J. Burrows, Michael P. Doyle, Nicole S. Sampson, Gary B. Schuster page 9), 2015 marks another 150-year mile- Editor-in-chief Copyright 2015, American Chemical Society Canadian GST Reg. No. R127571347 Volume 93, Number 18 Views expressed on this page are those of the author and not necessarily those of ACS.

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cells, where it turned on protective genes that pre- DNA CONJUGATES vented liver injury. DART INTO CELLS These DARTs contained a short DNA sequence that binds Nrf2. To this DNA strand, the researchers at- DRUG DISCOVERY: tached hydrophobic alkyl chains that are protected by New acid-sensitive linkers and galactose end-caps. Mask- method delivers therapeutic ing the hydrophobic alkyl chains prevents them from transcription factors to cells disrupting membranes in nontarget cells, which could cause side effects. The galactoses also allow the DARTs to bind to receptors on liver cells and then scoot into RANSCRIPTION FACTORS control how cells liver-cell endosomes. Once inside, the acidic environ- work because they activate specific genes to pro- ment breaks the acid-labile linkers. This unmasks the T duce proteins. If used as drugs, the factors could hydrophobic alkyl chains, allowing them to disrupt en- be equally powerful by boosting underperforming dosome membranes by a surfactant-like process. En- cellular activities or turning on genes to treat medical dosome disruption releases DARTs into the cytoplasm conditions or diseases. and then the nucleus, where they activate antioxidant But delivering transcription factors to specific cells and anti-inflammatory genes that protect against liver or tissues without toxic side effects has proven diffi- damage.

cult. Now, bioengineer Niren Murthy of the University Nrf2

OH HO OH HO O O O HO O HO OH N N OH N N N O O N N N O O N O N OH N O N O HO O N O N OH HO H H O O N N O O O N N HO N N HO OH OH

Galactose group Acid-labile linkage Endosomal disruption DISRUPTIVE TECHNOLOGY This DART consists of the transcription factor Nrf2 bound to a DNA of California, Berkeley, and coworkers demonstrate strand, a hydrophobic group that disrupts endosome how to safely smuggle transcription factors into liver MATER. NAT. membranes, an acid-labile linkage, and a galactose cells using a method that could also work for a wide group to target the assembly to liver cells. range of other cell types. The Murthy group’s concept involved targeting José Manautou of the University of Connecticut, an

transcription factors to specific cell-surface receptors FROM ADAPTED expert on liver toxicity who has studied Nrf2 activa- on liver cells that would shepherd the cargo into cell tion, comments that the technique seems powerful compartments called endosomes. The factors would for deterring liver toxicity following acetaminophen then break out of the endosomes so they could enter administration. But he points out that the mice were the cytoplasm and then the nucleus, where they could treated with DARTs only an hour after administration perform their gene-activation magic. of acetaminophen—sooner than would be practical for To make the magic happen, the researchers designed addressing most cases of acetaminophen poisoning in and synthesized DNA-assembled recombinant tran- people. It remains to be determined, he says, if DARTs scription factors, or DARTs (Nat. Mater. 2015, DOI: will work as well if administered later, when they might 10.1038/nmat4269 ). A DART has a set of three major need to reverse liver damage, not just prevent it. Nev- components that can bind the transcription factor of ertheless, it’s “a novel and promising technology that choice, deliver it to endosomes in a specific cell type, warrants further evaluation,” he says. and then break apart endosomes to give the factor ac- The modular structure of DARTs makes it possible cess to the nucleus. to customize them to carry other transcription factors The researchers tested the technique by inject- besides Nrf2 and target other types of cells besides liver ing DARTs into mice that had been given a dose of cells by changing the DNA strand and end-caps, respec- acetaminophen sufficient to cause liver damage. The tively. Murthy says his team is improving DARTs’ effica- DARTs delivered a transcription factor called nuclear cy and testing them in mice with chronic liver disease in erythroid 2-related factor (Nrf2) directly to the liver hopes of moving them to clinical trials. — STU BORMAN

CEN.ACS.ORG 5 MAY 4, 2015 NEWS OF THE WEEK

authority to restrict significant new uses of a chemical.” CHEMICAL REFORM The chemical sector, on the other hand, is applauding BILL ADVANCES lawmakers for hammering out a bipartisan deal. Calvin M. Dooley, president and CEO of the American Chemis- CONGRESS: try Council, an industry group, says the compromise bill Senate panel clears “reflects a carefully balanced approach that incorporates compromise that would update interests of several Democratic senators and maintains law on commercial substances important priorities for manufacturers.” “Updating the outdated, inefficient TSCA will better

U.S. CONGRESS (BOTH) CONGRESS U.S. protect the safety of our families and also advance inno- AWMAKERS ON Capitol Hill have taken a major vation in our economy,” says Sen. David B. Vitter (R-La.), step toward overhauling the nation’s outdated who introduced S. 697 with Sen. Tom S. Udall (D-N.M.) L law governing commercial chemicals. A Senate in March. committee on April 28 approved a bipartisan bill to re- Initially, the bill didn’t sit well with other Demo- form the 1976 Toxic Substances Control Act (TSCA). crats. But Sens. Jeff A. Merkley (D-Ore.), Sheldon Vitter Because a handful of Democrats support the mea- Whitehouse (D-R.I.), and Cory A. Booker (D-N.J.) sure, the legislation, S. 697, stands a solid chance of pas- negotiated a compromise with Republicans that ad- sage by the Republican-controlled Senate. dresses a number of concerns activists and some state Both the and advocacy groups officials raised about state laws on chemicals. In par- for years have pressed Congress to modernize TSCA, ticular, the newly approved bill would allow states, in though they don’t see eye to eye on S. 697. certain circumstances, to regulate chemicals while EPA Environmental and health activists say the measure, is evaluating the safety of those substances. which the Senate Environment & Public Works Com- “This bipartisan agreement greatly strengthens the mittee approved 15-5, is an improvement over previous ability of states to protect citizens from toxic chemi- TSCA reform bills. But they say it still falls short in some cals when the federal government has failed to do so,” provisions. For instance, Andy Igrejas, director of Safer Merkley says. Chemicals, Healthy Families, an environmental and pub- Senate leaders have yet to decide when to bring the Udall lic health coalition, says S. 697 would “roll back EPA’s bill to the chamber’s floor for a vote. — BRITT ERICKSON

are onto something in their critique.” Trian aggres- ADVISORY SERVICES sively promotes change at companies in which it takes a BACK DUPONT FOE stake. Its targets have included PepsiCo, industrial con- glomerate Ingersoll Rand, and food maker Danone. STRATEGY: In a letter to DuPont shareholders, Trian hails ISS’s Two of three advisers say voting recommendations, saying it is pleased that the Trian Fund Management should advisory service agrees that “change is needed on the get seats on DuPont’s board DuPont board.” But Trian added that all four of its nominees “are needed in the DuPont boardroom.” Peltz and Trian have argued that DuPont’s overhead CTIVIST INVESTOR GROUP Trian Fund Man- costs are too high and that the firm ought to be broken agement has won the partial backing of two vot- up. ISS gives some credence to that take: “Operating effi- A ing advisory services in its contest to win seats ciency is not what it should be, yet instead of addressing on DuPont ’s board of directors at the company’s May 13 the core issues, the [DuPont] board and management, annual meeting. However, a third service rejected all at least in their communications with shareholders, are four Trian candidates. more inclined to obfuscation than accountability.” DuPont is downplaying the value of the support for DuPont disagrees. “We strongly believe ISS reached Trian’s directors and says shareholders will make up the wrong conclusion,” the company says. The com- their own minds when they vote. pany also says Glass, Lewis erred “in failing to recom- The most influential of the three advisory services, mend a vote for all 12 DuPont nominees.” JASON COHN//NEWSCOM JASON Institutional Shareholder Services (ISS), recommends In attempting to unseat four DuPont directors, Trian Peltz that shareholders elect two of Trian’s four board “would deprive DuPont’s board of critical skills that are nominees, including Trian CEO Nelson Peltz. Advisory central to DuPont’s purpose and value proposition,” service Glass, Lewis & Co. recommends a vote for Peltz the company claims. but none of the other Trian nominees, while the third DuPont also points out that institutional sharehold- service, Proxy Mosaic, rejects all four Trian nominees. ers, who control about 70% of its stock, don’t always In its assessment of DuPont, ISS notes that “this is accept advisory service recommendations. “We are not a broken company,” as Peltz has suggested, but con- confident that shareholders will do their own analysis,” tends “there is compelling evidence that the dissidents the firm says. — MARC REISCH

CEN.ACS.ORG 6 MAY 4, 2015 NEWS OF THE WEEK

used by the beetle,” says Andrew McIntosh , a thermo- BEETLE’S dynamics professor at England’s University of Leeds. McIntosh has studied bombardier but was not SPRAY REVEALED involved in the current work. He notes that the study confirms earlier research that suggested valves play a BIOWEAPON: Pulsed mechanism role in the beetle spray explosions. driven by chemical reaction The experiments were carried out by Massachusetts Institute of Technology graduate student Eric M. Arndt and professor of materials science O FEND OFF PREDATORS, bombardier beetles and engineering Christine spray a hot, irritating liquid from a gland that Ortiz, University of Arizona T behaves like a microscopic chemical reactor. entomology professor Wen- Researchers have now used synchrotron X-ray imag- dy Moore, and Brookhaven ing to reveal details about how the beetles control National Laboratory scien- their built-in weapon ( Science 2015, DOI: 10.1126/ tist Wah-Keat Lee. science/1261166 ). The method they devel- The beetles’ pygidial glands have multiple parts, oped was to anesthetize a including a reservoir chamber, a reaction chamber, beetle by cooling it down, and an exit channel. The reservoir chamber contains then use modeling clay to hold it on an aqueous solution of 25% , 10% a mount. “When the beetle warms up, it realizes that Bombardier beetles p-, and 10% alkanes. The reaction it’s fixed in place, so it gets scared” and releases its (top) produce a hot, chamber contains peroxidase and enzymes. explosive spray, Ortiz says. The researchers were able irritating spray of benzoquinones When a beetle goes into defensive mode, it transfers to obtain X-ray images of the spray explosions at 30 to from their the reservoir fluid into its reaction chamber, where 2,000 frames per second. pygidial glands, enzymatic reactions produce p -benzoquinones—the Muscles within the reservoir chamber contract to shown stained irritating component of its spray—along with oxygen push fluid into the reaction chamber. But only a little in a micrograph and heat. Water vaporizes, pressure builds up, and the fluid goes in at a time, in the form of 5-nL droplets, (bottom). spray explodes from the exit channel. For one particu- the team found. As soon as fluid lar group of bombardier beetles, spray explosions come enters the reaction chamber, the

out at about 100 °C, with a velocity of 10 meters per enzymes within immediately go (BOTH) second and a range of several centimeters. They also to work, and the rising pressure pulse as quickly as 700 Hz. serves both to close a valve be- But how the beetles control their complex machin- tween the reservoir and reaction SCIENCE ery has been a mystery. The new work “is the first inter- chambers and to blast the spray nal experimental analysis of the intricate mechanism out the exit. Then the reduced pressure allows the valve to re- open for another cycle. “It’s a very VIDEO ONLINE efficient way of controlling the View X-ray video of a beetle ejecting its defensive pulse explosion,” Ortiz says.— spray at cenm.ag/beetle. JYLLIAN KEMSLEY

EXPORTS Trade fight looms as key bills head for House and Senate votes

Congressional committees recently completed TPP deal to Congress for an P. Walls, vice president of regulatory agreed to give President Barack Obama up-or-down vote, rather than allowing and technical affairs at the American the authority he needs to wrap up the lawmakers to amend it. Chemistry Council, an industry trade Trans-Pacific Partnership (TPP), the pro- Without this fast-track procedure, ana- association. posed free-trade pact between the U.S., lysts say that no trade partner will make The fast-track mechanism will “help Japan, and 10 other countries mostly in concessions to U.S. negotiators because open markets and ensure the U.S. chemi- the Asia-Pacific region. Congress could pick the deal apart. cal industry can capitalize on its massive But the real fight over the legislation The chemical industry, one of the na- export potential,” Walls adds. (S. 995 and H.R. 1890) will occur in the tion’s top exporting sectors, supports But the legislation faces strong op- coming weeks when the controversial both the legislation and the TPP. position from the labor movement and its measure comes up for final votes in the “For U.S. chemical manufacturers to Democratic allies, who argue that trade Senate and the House of Representa- succeed in today’s global economy, we agreements have caused an outflow tives. The trade promotion bill would must be able to compete effectively in of manufacturing jobs from the U.S. to allow President Obama to submit the international markets,” says Michael other nations. — GLENN HESS

CEN.ACS.ORG 7 MAY 4, 2015 NEWS OF THE WEEK

which help remove methyl groups from cytosine bases in NEURONS TWEAK DNA, are involved in memory formation. DNA CONSTANTLY In the new study, Hongjun Song of Johns Hopkins University School of Medicine and colleagues found EPIGENETICS: that one of these enzymes, Tet3, helps tune how neurons Demethylation respond to signals from their neighbors ( Nat. Neurosci. enzyme helps regulate 2015, DOI: 10.1038/nn.4008 ). When the researchers neuronal communication reduced the amount of Tet3 expressed in cultured neu- rons, the cells’ responses to incoming signals got larger. Overexpressing the enzyme had the opposite effect. EURONS MAY MODIFY their DNA on a regular Through further experiments, the team found that basis to adjust their level of activity, a new study Tet3 influences neuronal responses by somehow con- NH 2 N reports. The cells change the pattern of methyl trolling the number of glutamate receptors at a nerve N groups on their DNA to strengthen and weaken the cell’s synapses. For example, adding receptors strength- connections—or synapses—they make with ens synapses and allows cells to amplify their responses. O N their neighbors. Changing the strength of synapses, neuroscientists DNMT Tet The findings provide more support think, is a key step in learning and memory. And Tet3 ap- Methylation 5-mC Oxidation for the idea that DNA modifications, pears to tune synapses as part of a process to ensure neu- known as epigenetics, may play a ronal activity doesn’t get too high or too low. If neurons DNA m ethyltransferases fundamental role in learning become excessively active or inactive, they are less able NH NH 2 (DNMT) add methyl groups 2 and memory. to respond to signals from their neighbors. N to cytosine. Tet enzymes N OH For a long time, biologists Neurons are taking some big risks using demethyl- oxidize 5-methylcytosine, thought DNA methylation was ation to control their activity, says Li-Huei Tsai, a neu- O N generating bases such as O N 5-hydroxymethylcytosine, static in fully developed cells roscientist at Massachusetts Institute of Technology. which then get replaced such as neurons. But in the past Demethylation requires oxidizing methylated DNA, so Cytosine with cytosine. 5-hmC decade, researchers have found there are plenty of opportunities for the cellular machin- evidence that these DNA methyla- ery to accidentally damage DNA and create mutations. tion patterns are more fluid than previ- “I wonder if by engaging in this risky business, neu- ously thought. In particular, some studies rons set themselves up for degeneration over time,” Tsai Tet + DNA repair enzymes have shown that enzymes called Tet proteins, says. — MICHAEL TORRICE

White House has threatened to veto the legislation. ROADBLOCK FOR Sen. John Barrasso (R-Wyo.), sponsor of S. 544, says POLLUTION RULES the measure “will give Americans more confidence that EPA’s policies will deliver the environmental and public CONGRESS: health benefits the agency has promised.” Senate panel advances Republicans are pushing the bill in large part because bill requiring EPA to use only publicly EPA failed to provide congressionally requested raw Critics say a bill available and reproducible data would hamper health data from studies the agency used to review the EPA’s ability to risks of particulate matter air pollution. The agency says regulate air and information about individual participants remains un- other pollution. EGISLATION THAT WOULD undercut EPA’s abil- der the control of the institutions that did the research. ity to regulate pollution in air, water, and soil got “It would be good to see thoughtful legislation that Lapproval from a Senate panel last week. The bill advances data access while addressing the complexity would force EPA to rely only on health research that is and costs of doing so,” says Dan Greenbaum, president publicly available and reproducible. of the nonprofit Health Effects Institute, which is jointly The bill seemingly would impose uncontroversial funded by EPA and the automotive industry. The Con- SHUTTERSTOCK data-sharing requirements on EPA. But the legislation gressional Budget Office says S. 544 would cost EPA would force the agency to ignore credible health data $250 million a year to implement, but the bill only pro- because of the need to protect patient confidentiality, vides $1 million in funding, Democrats say. critics charge. “It’s a catch-22 to say you may not release Researchers are concerned that new mandates on health data and therefore you may not regulate based on EPA to release confidential health data would also that information,” says Andrew Rosenberg at the Union constrain recruitment for clinical health studies. Insti- of Concerned Scientists, an advocacy group. tutional review boards that examine plans for studies The Senate Environment & Public Works Commit- involving human subjects “would take this very seri- tee’s 11-9 party-line vote on S. 544, the so-called Secret ously and tell researchers, ‘You can’t guarantee subjects’ Science Reform Act, echoes a companion bill, H.R. 1030, confidentiality if Congress wants to access your health which the House of Representatives passed 241-175. The information,’ ” Rosenberg says.— STEVEN GIBB

CEN.ACS.ORG 8 MAY 4, 2015 NEWS OF THE WEEK

gave the gelation agents time to fix the flakes into a po- GRAPHENE THAT’S rous framework. FIT TO PRINT Once the printer finished, the team replaced the iso- octane with air, etched away the silica, and was left with Livermore researchers 3-D MATERIALS: New inks create supercompressible aerogels with large surface areas printed graphene and good conductivities, Worsley says. These proper- aerogels of promising structures for energy ties make the aerogels attractive for batteries, capaci- different shapes

storage and tissue regeneration tors, and hydrogen fuel cells. and sizes. NAT. COMMUN. Instead of printing into a solvent bath, the Northwestern ESEARCHERS HAVE PRINTED inks containing team, led by Ramille N. Shah, nanoscopic graphene flakes to build macroscop- used several solvents in its R ic, three-dimensional objects that they say could graphene ink, along with a bio- benefit numerous fields, including energy storage and compatible elastomer. bioengineering. One of the ink’s solvents, A team at Lawrence Livermore National Laboratory dichloromethane, evaporated has 3-D printed porous, highly compressible aerogels quickly to fix a printed layer in using a graphene oxide ink (Nat. Commun. 2015, DOI: place. But the remaining solvents, 2-butoxyethanol 10.1038/ncomms7962 ). And researchers at North- and dibutyl phthalate, evaporated at a slower rate and western University designed tissue scaffolds with kept that layer wet enough to adhere to the next layer Scientists at ink that contains graphene flakes within a flexible, printed on top of it. Northwestern biocompatible polymer (ACS Nano 2015, DOI: 10.1021/ After the ink dried, two components remained: University acsnano.5b01179). graphene flakes and a polymer called polylactide-co - can print their graphene-based These are not the first examples of graphene inks. glycolide. This allowed the team to print flexible scaf- ink into complex However, scientists are still searching for formulations folds that could be cut to size and sutured into living tis- shapes, such that fully capitalize on the atomically thin material’s sue to support cell growth and tissue regeneration with- as this 1-inch- remarkable properties. For example, some existing out eliciting any severe immune response, Shah says. diameter skull. inks sacrifice mechanical properties for high electrical The conductivity of the scaffolds also appears conductivity. to facilitate cell signaling and differentiation, “We were really trying to avoid making compro- she adds, but the long-term health effects of mises,” says Marcus A. Worsley, who led the Livermore such implants still needs to be evaluated. researchers along with his colleague Cheng Zhu. Their Developing 3-D printable graphene inks is goal was to devise a 3-D printing process that allowed an important undertaking, clearly evidenced conductive flakes to controllably coalesce and ulti- by the attention it’s now receiving, says mately form aerogels: spongelike materials that are Esther García-Tuñon Blanca, a materials about as light as air yet mechanically robust. researcher at Imperial College London who Their ink contained water, graphene oxide flakes, was not involved in either study. “The more silica filler particles, and a gelation agent, such as am- research groups working with it, the sooner monium carbonate. By printing the ink in a bath of we all find out the actual potential graphene

isooctane, the team prevented the ink from drying and has in everyday life.” —MATT DAVENPORT UNIVERSITY LAB/NORTHWESTERN JAKUS/SHAH ADAM

INDUSTRY BASF 150th anniversary event punctuated by sharp words from Angela Merkel

In an event that at times felt more like dience of about 1,000 people by ripping public performance of “Water Dances,” a a wedding than the anniversary of the into the company for inventing chemical symphony written for BASF’s anniversary founding of a major chemical company, weapons used in the First World War and by British composer Michael Nyman. It leaders of German industry and politics for making the gas used to murder Jews was played by London’s Royal Philhar- gathered in Ludwigshafen to toast the in the Second World War. “In the history monic Orchestra. The performance was success that is BASF , the world’s largest of BASF, we see reflections of our country, prefaced by a musical montage, recorded chemical company. including its darker moments,” she said. by Nyman, comprising some of the actual The celebration took place on April 23 , In the end, Merkel managed to receive sounds of BASF—everything from ma- almost 150 years to the day after the a standing ovation from the largely Ger- chines whirring to water flowing . firm was founded. Guests included Ger- man audience by also stressing how im- If there is such a thing as the sound man Chancellor Angela Merkel—who also portant BASF is as a force for innovation of chemistry, then perhaps this was it. If holds a doctorate in physical chemistry— in a world faced with limited resources there was a defining event for celebrating and Bayer Chairman Marijn Dekkers. and a growing population. the chemistry enterprise, then perhaps In her speech, Merkel silenced the au- Merkel’s exit was followed by the first this was it as well. — ALEX SCOTT

CEN.ACS.ORG 9 MAY 4, 2015 COVER STORY INDIA: UNDER NEW MANAGEMENT In power for a year, the administration of Prime Minister Modi is promising to DELIVER CHANGE TO INDIA JEAN-FRANÇOIS TREMBLAY , C&EN HONG KONG

SWORN IN NEARLY a year ago, Prime Minister Narendra Modi has raised expec- GUJARAT tations in India after years of economic and An industry-friendly state within driving distance of Mumbai, Gujarat produces social stagnation under ineffective coali- about half of India’s chemicals. tion leadership. Modi’s ambitious new government 1 Jamnagar Delhi hopes to raise living standards for the poor, Reliance Industries operates India’s largest The city of 16 million is home modernize cities, improve public health oil refinery here. It is integrated with a petrochemical complex that will soon to the national government, and sanitation, improve education, and import U.S. ethane gas to feed its crackers. led by Prime Minister deliver steady and strong economic growth Narendra Modi since without harming the environment. Over 2 Dahej May 2014. Backed by a strong the past year, Modi has toured the world in This port and industry park is the site of electoral mandate, the Modi his quest for foreign friends and investors India’s most-developed government- administration aspires to who can help him achieve his dream for promoted chemical industry zone. boost economic growth by India. 3 Vapi simplifying regulations and Of course all new administrations have This industrial center, which contains many raising government efciency. lofty goals. But according to those who pigment and dye makers, was for years on have met Modi or members of his team, the a list of the world’s 10 most polluted places new government seems to have the disci- (see page 14). pline and work ethic to pull them off. Modi Bhopal is said to hold regular meetings lasting GUJARAT Thousands of people died several days at which he grills senior public in 1984 in the world’s servants on what they are doing to promote 1 worst-ever industrial growth in India. Under pressure to deliver, 2 accident when a cloud of officials are seeking input from industry methyl isocyanate gas executives on how to remove impediments escaped from a Union 3 to growth. Usually ignored, leaders of the Carbide insecticide plant. Indian chemical industry are delighted to Modi’s India be included in the consultation process. Several cities play key roles Modi has taken charge at an auspicious in India’s chemical and time for the chemical industry in India. pharmaceutical industries. Integrated industry zones that have long been discussed are finally coming together. Demand is strong for everything from Mumbai Hyderabad plastics to crop protection chemicals. And With a population of The capital of Andhra Pradesh state is new petrochemical complexes are opening 21 million, India’s business India’s pharmaceutical production hub. across the country, improving local avail- center is home to major Hundreds of plants producing active ability of needed raw materials. chemical and drug ingredients and finished drugs operate in or companies, including near this city of nearly 8 million. Companies The first of the two stories in the pages Reliance Industries, Sun with headquarters here include Dr. Reddy’s to follow offers the chemical industry’s Pharma, and Cipla. Laboratories and Aurobindo. take on where India is going and what it needs to do to succeed. The second is a look at how the Modi administration in- tends to balance environmentalism and economic growth in an Indian city where, in years past, industry ran amok.

CEN.ACS.ORG 10 MAY 4, 2015 Indian Chemicals At A Glance INDUSTRY TURNS ◾ Sixth-largest producer of chemicals in OPTIMISTIC the world, third-largest in Asia after China and Japan Even if it has done little so far, INDIA’S NEW GOVERNMENT ◾ $144 billion total chemical market size, according to the Indian government has improved the outlook for chemicals ◾ Number one in FDA-approved drug manufacturing plants outside the U.S. ◾ 9% chemical industry average growth IT’S CLEAR UPON LANDING on a flight to rennial obstacles to business, executives rate over the past five years Mumbai that things are changing in India. are beginning to shed their doubts. The city, India’s largest, recently completed “Now is the best of times for the Indian the construction of an immense and mod- chemical industry,” said Sudhir Shenoy, ern international terminal. Long lines for head of Dow Chemical’s operations in Haldia passport inspections and security checks India, speaking at a conference organized This small city near Calcutta is home to a are, to the relief of many, a thing of the past. by India’s Chemical Weekly magazine last medium-sized petrochemical maker, Leaving the airport reveals what is still month. “The new government has im- Haldia Petrochemical (now part of Gail), the same. Like most Indian cities, Mumbai proved the outlook, so the industry could as well as MCC PTA India, a producer of lacks an efficient mass transit system, so grow at 10, 15, or even 20% in coming years.” purified terephthalic acid majority-owned only in the dead of night are streets uncon- It will be growth from a small base. by Mitsubishi Chemical. gested. Distances and travel times need to Although India is home to one-sixth of be carefully considered in order to arrive the world’s population and is Asia’s third- on time at appointments in the vast city. largest economy after China and Japan, the Indeed, many of the old stumbling blocks country has a tiny chemical industry that to doing business in India are still there. But accounts for only about 3% of world chemi- for the country’s chemical sector, the out- cal output, according to Tata Strategic Man- look has shifted under the administration agement Group, an Indian consulting firm. of Prime Minister Narendra Modi, who took Dow and other companies seeking to office a year ago. Whereas in years past Indi- increase that figure will be buoyed by Growth Drivers an chemical company executives tended to initiatives championed by the new gov- Infrastructure: The quality of infrastructure see an array of hurdles to economic success, ernment, Shenoy said. For instance, the has long hindered industry growth. The the mood today in Mumbai, also the na- chemical industry can only benefit from government is promoting chemical industry tion’s business capital, is definitely upbeat. the Modi administration’s zones, as well as an improved road and rail Even before Modi’s election, growth goal to build 100 “smart network. in the Indian chemical industry had ac- cities”—places where BUSTLING Government: The new Modi government celerated to an uncharacteristically strong such things as traffic India’s traffic, has boosted business confidence by listening 9% per year, compared with the 2005–10 flow, trash collection, and shown here in to industry leaders. It is promising to spur period when chemical production barely transit system operation Mumbai, is a growth through administrative reforms, sign of both expanded. Now, with a government that are centrally monitored vibrancy and accelerated investment in infrastructure, and appears to be serious about removing pe- and controlled through chaos. increased power generation. Urbanization: Farmers are moving into cities, raising demand for transportation, construction materials, and treated water. The Modi government has called for the creation of 100 “smart cities” that are expected to feature modern urban transit systems and advanced energy and water management. Oil Industry: Indian oil companies are adding petrochemical complexes to their refineries to maximize value. Technology: Farmers, who represent 60% of India’s population, have been investing in crop protection to boost yields. The Indian government is expected to invest in water quality, boosting demand for necessary

SHUTTERSTOCK/C&EN treatment chemicals and polymers. TREMBLAY/C&EN JEAN-FRANÇOIS

CEN.ACS.ORG 11 MAY 4, 2015 COVER STORY

comprehensive information technology. with Singapore, even though the city-state eling 200 miles in small-capacity trucks on Although other executives at the confer- has a small market for chemicals and no in- bad roads. We need pipelines,” he said. ence shared some of Shenoy’s enthusiasm, digenous source of natural gas or crude oil. But on the whole, Stilliard has a posi- many are skeptical that unbridled opti- Industrial growth is hampered by myri- tive outlook for the chemical industry in mism is warranted at this early stage of the ad regulations, such as those that prevent India under the Modi administration. “The Modi administration. The critical problem foreign ships from ferrying cargo from one interest of the Indian government in the of India’s poor infrastructure will take a Indian port to another, added Matthew chemical industry is almost unprecedented long time to solve, they pointed out. George, head of petrochemical exports at anywhere in the world,” said Stilliard, a Stephan Pilz, vice president of busi- Indian Oil Corp., a large state-controlled British-born chemical industry veteran who ness development in India for Germany’s refiner. Using the Indian companies that has been at Huntsman for 15 years. Evonik Industries, noted that the World control coastal shipping is slow and expen- Bank presently ranks the country 134, out sive, he added, and partly explains India’s THE PHARMACEUTICAL chemicals sec- of 183, in ease of doing business. The chem- overreliance on trucks. It’s a dynamic that tor could also shine if certain reforms ical industry in India is challenged by im- won’t be easy to change, George said. “In- are implemented, said Dinesh Dua, chief pediments such as an inverted import duty dia has many lobbies. The local shipping executive officer of Nectar Lifesciences , structure that discourages manufacturing. industry opposes opening the market.” an antibiotics manufacturer. Indian com- “Custom duties are currently 8% on spi- The simple act of sending chemicals from panies have a better understanding than nal implants made with PEEK”—polyether one plant to another is a challenge for for- their Chinese counterparts of regulations ether ketone, an engineering plastic—“and eign companies, concurred Steve Stilliard, in developed countries and how to make 30% on PEEK resin,” Pilz noted. “So who managing director for India at the U.S. complex active pharmaceutical ingredients will import PEEK to make implants in In- chemical maker Huntsman Corp. “Head- (APIs), according to Dua. But in recent dia?” He also observed that India compares quarters will never approve an investment years, generic drug makers in India have unfavorably as an investment destination plan that involves hazardous materials trav- become increasingly reliant on China.

BASF IN INDIA office, BASF has started con- struction near Mumbai of an Local Manager Of World’s Largest Chemical Firm R&D facility that will accom- Is Encouraged So Far By The Modi Administration modate as many as 300 sci- entists when ready in 2017. “As The views of Raman Rama- New Delhi, are now far more ing every Indian access to a the economy expands in India, chandran, managing director disciplined, with emphasis toilet within a few years. BASF will invest to capture of BASF India, have weight on stricter deadlines and be- The Make in India campaign the big growth opportunity given his company’s size—it’s ing approachable. Among its aims to stimulate manufactur- that the country will offer,” Ra- the world’s largest chemical first moves, Prime Minister ing and industrial growth. But machandran says. maker—and its already sub- Narendra Modi’s administra- it’s also a social campaign, giv- Still, BASF is not planning stantial presence tion combined 17 en that manufacturing could one of its major integrated in the country. related ministries provide much-needed employ- Verbund complexes in India to BASF Ramachandran says into seven groups. ment to young adults. Every produce upstream petrochem- he sees a lot to like And bureaucrats year, Ramachandran notes, icals and basic chemicals. He about the new cen- are now empow- 10 million to 20 million youths says the main hurdle is not tral government in ered to make enter the job market. infrastructure, the top chal- India. more decisions, And through his much- lenge cited by most chemical “For the past which he expects publicized trips to foreign company managers in India. year, there has been to speed up the countries, Modi does more It’s mostly that the size of the a sense of optimism implementation of than promote investment and Indian market does not yet in India about the long-planned in- meet Indians living overseas. warrant such a commitment whole economy,” Ramachandran vestment and infra- For instance, during his recent from BASF, Ramachandran he says. “For the structure projects. visit to Germany, he both met says. And when the time first time, the government has The new administration with industry captains and ex- comes, “the issues pertaining come out with a much more has come up with a number plored the possibility of work- to feedstock and raw material comprehensive approach on of initiatives that add up to ing with Germany on skills availability will also have to be a number of social and eco- an integrated approach to development, an area in which addressed,” he notes. nomic aspects of the country economic and social devel- the country excels. But in view of the high and is really trying to make it opment, even if most policy In India, BASF employs growth rates India is expected happen.” details are for the moment close to 2,200 people and op- to experience in the coming To start with, he says, the missing. For instance, a Clean erates nine production facili- years, BASF may well decide to government looks differ- India campaign aims to im- ties across the country. Since tackle those practical challeng- ent. Ministries in the capital, prove public health by provid- the Modi administration took es sooner rather than later.

CEN.ACS.ORG 12 MAY 4, 2015 LEADER Modi, here on a recent trip to Germany, has won the In the near term, Manish Panchal, pand in highly polluted areas (see page 14). confidence of India’s chemical practice head for chemicals and energy at But the government will deliver, Panchal industry. Tata, cautioned that business confidence predicted. “I’ve never seen the Indian gov- is likely to drop in the coming months ernment working so hard,” he said. When because the Modi government has cre- it comes to the economy, the government’s ated sky-high expectations while so far immediate focus is to make it easier to do delivering little except promises. Among business in India. At this juncture, foreign its few concrete changes is a contro- chemical companies that don’t have a pres- versial move to allow companies to ex- ence in India should consider an acquisi-

“I used to make my own intermediates, but Chinese costs are 50% lower,” Dua said. Producers in China have access to the well-developed infrastructure of industrial parks as well as cheap and reliable electric- ity, he noted. If for one reason or another—a crack- down on pollution, for example—Chinese producers of pharmaceutical ingredients stopped shipping to India, the country’s

REYNALDO PAGANELLI/SIPA/NEWSCOM REYNALDO generic drug industry would be wiped out, Dua warned. But he’s heartened that the new government seems to share the drug industry’s concerns about relying on China. The Modi administration has promised to improve infrastructure—including effluent treatment—at seven industrial clusters and to provide financial incentives to the indus- try, Dua said. “If all this is done by this absolutely busi- ness-friendly government, we will not only be self-sustaining in APIs, we will also push China 10 to 15 years behind us,” he said. Experts at prominent consulting firms agree that the Indian chemical industry is positioned for spectacular growth in the near future. Alok Verma, director of strat- egy at PricewaterhouseCoopers , said the overall Indian economy could grow sus- tainably at 9% per year if certain reforms are made. In its latest predictions, the International Monetary Fund said the In- dian economy will expand by 7.5% in 2015, surpassing China’s growth. And if the overall economy expands by 9% annually, the chemical industry should grow at close to 15%, Verma pointed out. The government will do what is required to facilitate growth, he predicted, partly because India’s high birthrate requires it. “If we don’t create 240 million new jobs in the coming 20 years, we will face a demo- graphic nightmare,” he warned.

CEN.ACS.ORG 13 MAY 4, 2015 COVER STORY

ON THE MOVE Industry and citizenry coexist uneasily in the polluted city of Vapi. JEAN-FRANÇOIS TREMBLAY/C&EN JEAN-FRANÇOIS

tion, he advised. And those that are already present should get ready to produce chemi- cals for export. NEW APPROACH IN VAPI The Indian chemical industry is buoyant for reasons beyond the feel-good influ- To promote growth in one of its most polluted cities, ence of the new Modi administration, said India tries lifting a BAN ON INDUSTRIAL EXPANSION Gaurav Moda, a partner at consulting firm KPMG India. For instance, the general move of India’s rural population to cities COMPARED WITH WHAT it was 15 years (CSE), a nongovernmental organization is resulting in demand for transportation, ago, Vapi seems to have cleaned up its act. in New Delhi. Kanchan conducted field re- clean water, and construction materials. Streams no longer change color depending search in Vapi in 2010 to measure pollution Another source of industry growth is on the time of the day. The city’s chemical there. “Government officials had tried to a trend by Indian oil companies to build industry, which includes several dye and implement other action plans before that,” petrochemical complexes alongside their pigment makers, has improved effluent he says, “but they weren’t effective.” refineries to increase the value they get collection so that most wastewater is sent One of India’s oldest chemical indus- out of crude oil. Between 2013 and 2018, he in for treatment instead of being dis- try clusters, Vapi is home to hundreds of expects, India’s petrochemical sector will charged into the closest stream. plants. Besides dyes and pigments, it’s expand by 13% annually. But the city, north of Mumbai in India’s known for materials including agrochemi- Among the companies building new proj- Gujarat state, remains one of the most cals and pharmaceutical ingredients. A few ects are Oil & Natural Gas Corp., Gail India, polluted in India. As a result, a decision big producers such as United Phosphorous and Hindustan Petroleum Corp. Some of last summer by the new administration and Aarti Industries operate there, but the these companies are newcomers to the pet- of Prime Minister Narendra Modi to lift a majority of companies are small to medi- rochemical industry, and their entry means moratorium on industrial expansion has um-sized firms. more options for buyers of basic chemicals. drawn much attention. Even if it’s a clumsy Vapi has long ranked as one of India’s With greater choice, bargaining power will and unfair way to control pollution, the most polluted cities. During a visit in 2000, shift to buyers, Moda expects, and lower blanket ban on industrial expansion had C&EN was easily able to find a stream prices will stimulate industrial growth. proven effective, environmentalists claim. that changed color from red to green at Whether created by the new govern- Lifting it will only raise pollution in a city different times of day and another stream ment or not, tremendous opportunities already saturated with it. that was deeply red ( C&EN, May 15, 2000, are emerging in India’s chemical industry, Vapi (pronounced Wappy) illustrates page 27). In 2013, India’s Central Pollution Moda contends, and the question becomes in vivid ways the challenge the new Modi Control Board ranked Vapi and another whether companies are ready to take ad- government faces in using deregulation Gujarat city, Vatva, as having the worst sur- vantage of them. For example, because the as a means to promote industrial growth. face water quality in India. chemical industry in India is highly frag- Growth in industrial clusters such as Vapi Between 2010 and 2014, companies mented, companies hoping to gain market has been frustrated by the moratorium. But operating in Vapi and other Indian cities share will have to establish a sophisticated lifting it could backfire unless the govern- deemed “critically polluted areas” were marketing and distribution infrastructure. ment remains vigilant. In already-polluted slapped, on and off, with blanket bans on It’s by no means assured that chemical Vapi, allowing expansion again could easily industrial expansion. Last June, less than a companies will rise to the occasion and result in worsening environmental quality. month after the Modi administration took take advantage of new opportunities in In- “In every part of India where a moratori- office, the Ministry of Environment, For- dia. But the government, Moda said, is in- um was put in place, pollution went down,” est & Climate Change lifted the ban in Vapi tent on “extending the red carpet to chemi- says Sanjeev K. Kanchan, a researcher at and seven other badly polluted areas. cal companies, rather than the red tape.” the Centre for Science & Environment The ministry said it lifted the expansion

CEN.ACS.ORG 14 MAY 4, 2015 bans because the Central Pollution Control Perhaps of most spectacular note, the Among its many pledges and slogans, Board in Delhi didn’t follow through on a Vapi water treatment plant, which is owned the Modi administration has advocated promise to review the methods used for by Vapi Industries Association, was hit with “zero defect, zero effect,” meaning that measuring pollution in the eight locations. a temporary suspension order last Decem- India should aim to produce high-quality Rohit Prajapati, an environmental activist ber after the Gujarat Pollution Control products without environmental impact. based in Vadodara, Gujarat, claims that the Board found that posttreatment water did Although environmentalists are skeptical, decision to lift the bans in fact happened not come close to meeting standards for it could be that, given time, a less environ- after intense lobbying by industry. biological and chemical oxygen demand, mentally harmful chemical industry will Although the ban has been lifted, com- two key environmental metrics. take shape in Vapi. ◾ panies hoping to expand in the polluted areas still have to apply for environmental clearance from the ministry.

LIFTING THE MORATORIUM means that the environment in Vapi will not improve, CSE’s Kanchan laments. “You have to hurt producers in their pockets, and then they will do something,” he says. It’s not the first time that the moratorium on indus- trial expansion in Vapi was lifted, he recalls. When it happened a few years ago, pollu- tion in the city quickly worsened. Even during the moratorium, enforce- ment of regulations was lax, adds M. S. H. Sheikh, an environmental activist based in the Gujarat city of Surat. Officers of the local environmental protection bureau rarely in- spect production facilities unless the public complains, he says. After delinquent facili- ties are ordered closed, Sheikh claims, they usually can resume production a few weeks later after a paying a small fine but without doing anything to reduce emissions. But Gaurav Moda, a partner at the con- sulting firm KPMG who works in the com- pany’s Global Chemicals Institute, sees some wisdom in lifting the moratorium. The city may be polluted, he says, but it has improved compared with a few years ago. And the environmental group Blacksmith Institute (now called Pure Earth) removed Vapi in 2009 from a list of the world’s 10 most polluted places. The moratorium served its purpose, Moda adds. Prevented from expanding in Vapi, many companies added facilities in other cities where they were required to use cleaner production processes. Compa- nies can now take these better processes to Vapi and expand without significant envi- ronmental impact, he reckons. And since the lifting of the moratorium, officials in charge of environmental protec- tion have proven to be strict against com- panies that violate regulations. Last month, Gujarat authorities ordered a two-month closure of 42 plants producing paper, phar- maceuticals, agrochemicals, and dyes for not complying with environmental norms and for failing to install monitoring equipment.

CEN.ACS.ORG 15 MAY 4, 2015 BUSINESS CONCENTRATES

CRODA TO PRODUCE BIO-ETHYLENE OXIDE TAKEOVER TRIANGLE AT IMPASSE will spend $170 mil- Generic drug firms Teva Pharmaceutical and Mylan keep upping the ante lion at its New Castle, Del., site to build in a clash of hostile takeover bids but have gotten no closer to ending their what will be the only commercial U.S. facil- impasse. Last week, Mylan rejected Teva’s $40 billion offer as too low and ity to dehydrate ethanol into ethylene and too risky because of stock value and antitrust issues. A merger “would then oxidize it to ethylene oxide. After the expose Mylan to a problematic culture and leadership with a poor record plant opens in 2017, the company plans to of delivering shareholder value,” Mylan’s board maintains. Combining the use the ethylene oxide to make nonionic number-one- and -four-ranked generic drug suppliers would also result surfactants entirely from sustainable feed- in “massive consolidation of supply and manufacturing, creating implica- stocks. Today, Croda produces surfactants tions for pricing power and shortages,” it added. Meanwhile, Mylan has at the site by reacting tropical oil deriva- made three offers to buy Perrigo , the most recent at nearly $36 billion. tives with synthetic ethylene oxide. The Perrigo has rejected all of them as undervaluing the company. With Mylan firm will use technology from Scientific making aggressive moves on Perrigo, Teva will likely have to increase its Design. “This investment represents a tidal offer price to win over Mylan. Teva faces a “long, drawn-out battle” that shift, especially for consumer goods manu- could last several months, says Evercore ISI stock analyst Umer Raffat, facturers who are striving for sustainability who doesn’t expect Teva to go much more than 10% higher. — AMT and performance,” says Croda CEO Steve Foots.— MM

with activist investor Starboard Value . battery electrolyte maker Novolyte Tech- HONEYWELL AND CEPSA Two existing directors stepped aside to nologies, sold to BASF in 2012.— MSR OPEN PLANTS IN CHINA make way for Starboard-backed directors including Louis Massimo, a former Arch Honeywell has started up a plant in Zhang- Chemicals executive. LSB says it now plans MEXICAN AND SPANISH jiagang, China, that will produce catalysts to separate its chemical business from its FIRMS BOOST VENTURE used to convert propane to propylene. In climate control products business and set up a master limited Mexico’s Grupo Kuo and Spain’s Repsol partnership for the are expanding their Dynasol synthetic This phenol and acetone plant is Cepsa’s first outside Spain. CEPSA chemical operations. elastomers joint venture. Dynasol, which In response to the the companies have run since 1999, makes news, credit rat- styrene-butadiene rubber and block copo- ing agency Moody’s lymers in Mexico, Spain, and, soon, China. revised its outlook To that, Kuo will add its Mexican nitrile and on the firm’s debt to emulsion rubber business and a nitrile rub- negative from stable. ber plant that is set to start up later this year Some of the director in Nanjing, China. Repsol will contribute changes are positive, its Spanish vulcanization accelerators busi- Moody’s says, but ness. With the new assets, Dynasol will have the past four years, the company says, it has many directors on the 13-member board about $750 million in annual sales.— AHT licensed its Oleflex process for propane “do not have plant-level manufacturing conversion to 30 companies worldwide, 25 experience.”— MSR of them in China. Propylene production in AIR PRODUCTS ethylene crackers is on the decline, Hon- WORKING WITH SUNY eywell explains, as petrochemical makers ARSENAL CAPITAL switch to natural gas as a raw material. Sep- SELLS OFF ADHESIVES Air Products & Chemicals will work with arately, the Spanish petrochemical produc- SUNY Polytechnic Institute’s Colleges of er Cepsa has started up a 250,000-metric- Arsenal Capital Partners has agreed to sell Nanoscale Science & Engineering and the ton-per-year phenol plant in Shanghai. The Royal Adhesives & Sealants to another pri- nonprofit Sematech to develop chemical facility can also produce up to 150,000 met- vate equity firm, American Securities , for mechanical planarization (CMP) slurries in ric tons of acetone per year.— JFT an undisclosed sum. Arsenal acquired Roy- Albany, N.Y. The CMP Center is expected to al in 2010. After internal investment and attract $5 million in investment over three eight acquisitions, the South Bend, Ind., years and support 50 jobs, according to LSB INDUSTRIES BOWS firm now has annual adhesives and sealants SUNY. At the center, Air Products will work TO ACTIVIST INVESTOR sales in excess of $600 million. Arsenal has on CMP materials for sub-10-nm integrated a long history of buying, building, and then circuit fabrication. Two Japanese com- LSB Industries, a maker of agricultural selling chemical businesses. Among them panies, Mitsubishi Chemical and Hitachi and mining chemicals, has named five new are plasticizer maker Genovique Special- Chemical, also recently agreed to work at members to its board to avoid a proxy fight ties, sold to Eastman Chemical in 2010, and the CMP Center. — AHT

CEN.ACS.ORG 16 MAY 4, 2015 BUSINESS CONCENTRATES

EVONIK INVESTS IN restitution to DuPont. The U.S. Justice De- begin clinical trials next year. Celgene will POLYMER TESTING partment had previously sought a $225 mil- pay $100 million for Quanticel plus mile- lion fine, and an earlier court decision stone payments of up to $385 million.— RM Evonik Industries has opened an applica- found Kolon liable to pay DuPont $920 mil- tion technology center for superabsorbent lion. DuPont filed suit against Kolon in polymers at its Krefeld, Germany, site. 2009. — MM … AND INVESTS IN Built at a cost of about $1 million, the CANCER THERAPIES center will permit efficient testing of the DOW FINDS BUYER FOR Celgene will pay AstraZeneca $450 million AGROFRESH BUSINESS to participate in development of MEDI4736,

EVONIK an anti-PD-L1 inhibitor for hematologic ma- Dow Chemical will sell its AgroFresh busi- lignancies. The pact will focus on combining ness to Boulevard Acquisition, a publicly the AstraZeneca antibody with products traded investment company set up by the in Celgene’s pipeline. Separately, Celgene private equity firm Avenue Capital Group. has paid Northern Biologics, a biotech firm AgroFresh sells a system that uses 1-meth- backed by Versant Ventures, $30 million ylcyclopropene to keep fruit from spoil- for rights to license oncology antibodies in ing. The $860 million price is nine times Northern’s pipeline and to acquire North- AgroFresh’s pretax earnings. When the ern. And Celgene has paid Agios Pharma- deal is completed, AgroFresh will become ceuticals $10 million to expand an earlier a public company traded on the NASDAQ pact to develop AG-881, a small molecule in Evonik’s new highly absorbent exchange, and Dow will initially retain a development to treat brain cancer. —MM lab includes polymers in both 40% stake. The sale is part of a Dow plan mannequins for baby diaper and to divest up to $8.5 billion in businesses by absorbent polymer WUXI CEO SEEKS TO testing. adult incontinence mid-2016.— AHT applications, the TAKE FIRM PRIVATE firm says. A high- light of the lab is a new mannequin test for CELGENE ACQUIRES WuXi Pharmatech, a Chinese provider of incontinence products.— MM GENOMICS SPECIALIST … drug R&D and manufacturing services, has received a takeover offer worth more than Celgene will acquire Quanticel Pharmaceu- $3 billion from founder and CEO Ge Li and KOLON ADMITS THEFT ticals, a privately held specialist in cancer Ally Bridge Group Capital Partners. WuXi OF DUPONT SECRETS drug discovery. The deal will give Celgene will form a committee to consider it. Li access to Quanticel’s platform for the sin- founded WuXi in 2000, expanding it into a South Korea’s Kolon Industries pleaded gle-cell genomic analysis of human cancer research outsourcing behemoth with more guilty in federal court in Alexandria, Va., as well as Quanticel’s lead programs target- than 8,000 employees and sales last year of last week to stealing trade secrets regard- ing specific epigenetic modifiers. The deal $674 million. Last week the firm announced ing DuPont’s technol- caps a 2011 collaboration between the com- that it is building the world’s largest dispos- ogy. The company was sentenced to pay panies, during which time Quanticel gener- able-bioreactor-based mammalian cell cul- $85 million to the U.S. and $275 million in ated several drug candidates expected to ture facility in the city of Wuxi, China.— MM

BUSINESS and construction uses, fermentation-based from Skokie, Ill.-based treat underserved medi- ROUNDUP for about $162 million. processes and systems. LanzaTech. cal conditions using 4D’s Nubiola makes specialty Cargill says it will use the AAV vector discovery EUROCHEM has se- inorganic pigments and technology to expand in BAYER MaterialScience platform. The partnership lected a site in St. John is the world’s largest pro- fermentation products has picked BioAmber was facilitated by QB3, the Baptist Parish, La., ducer of ultramarine blue, outside of food and feed. to supply biobased suc- a University of California for an up-to-$1.5 billion Ferro says. OPX will wind down after cinic acid for a new line of biotech accelerator where nitrogen fertilizer plant it the transition is complete biobased polyurethanes 4D is based. announced in 2013. The AKZONOBEL and ICL are in six to nine months. intended for textile ap- Russian company is now joining to produce 1.5 mil- plications. Bayer says the CALICO, the Google- looking for a buyer for lion metric tons per year CHINA STEEL of Taiwan Impranil waterborne poly- founded company fo- land in Iberville Parish of high-purity vacuum salt has agreed to put $46 mil- urethanes have renewable cused on therapeutics that it had purchased as a at ICL’s mining facility in lion into the construction content as high as 65%. for aging, will support possible site. Catalonia, Spain. The proj- of a 50,000-metric-ton- research at the Buck ect will also yield a smaller per-year ethanol plant ROCHE AND 4D Mo- Institute for Research FERRO CORP. will ac- amount of white potash. that will use as feedstock lecular Therapeutics will on Aging. Calico has the quire Nubiola Pigmentos, off-gases from a steel mill jointly discover and de- option to obtain rights to a Spanish provider of CARGILL has acquired in Kaohsiung, Taiwan. The velop adeno-associated discoveries made under pigments for plastics OPX Biotechnologies’ plant will use technology virus (AAV) vectors to research it supports.

CEN.ACS.ORG 17 MAY 4, 2015 BUSINESS

cripple the virus’s ability to replicate. But HBV has two more survival tricks STRIKING GOLD TWICE that make it more complicated to fight than HCV: The virus can evade detection by After discovering a game-changing pill for hepatitis C, modulating the host immune system, and in MICHAEL SOFIA has turned his attention to hepatitis B its most clever ploy, it leaves a reservoir of LISA M. JARVIS , C&EN CHICAGO viral DNA in the liver of its host. As Sofia ex- plains, even if replication is shut down, the reservoir allows the virus to bounce back THE CHANCES of any one chemist dis- zation. Although a handful of antivirals are with new viral proteins, genomic material, covering a drug that works—a molecule approved to treat HBV, they don’t work for and, ultimately, new viral particles. that is safe and improves people’s lives in a most people; those who do respond aren’t Sofia and his OnCore partners were meaningful way—are small. The chances of actually cured and have to take the pills for convinced that eliminating the virus would discovering an actual cure? the rest of their lives. require a drug cocktail that addresses each Minuscule. Sofia first started con- of those survival mechanisms—viral rep- Medicinal chemist Mi- templating how to cure hep- lication, immune system control, and the chael Sofia has managed to TEKMIRA atitis B while at Pharmasset, liver viral reservoir. With that goal in mind, beat the odds. He invented the Princeton, N.J.-based they set out to assemble a portfolio. what is now one of the most biotech where he discov- successful drugs in the ered sofosbuvir. THE TINY COMPANY was self-funded pharmacopoeia: sofosbuvir, Then, in 2011, Gilead put until mid-2014, when one of the original better known as Gilead Sci- down $11 billion to acquire investors in Pharmasset provided its first ences’ blockbuster hepatitis Pharmasset. Although Sofia round of external funding, allowing Sofia C virus treatment Sovaldi. was offered a job at Gilead, and his team to quickly acquire a collection For many people with HCV, he had learned during earli- of assets. the pill sliced the treatment er stints at big pharma firms One of their first purchases was OCB- time for the virus from a Sofia that he prefers a more en- 030, a sangamide-based cyclophilin inhibi- year to just 12 weeks while trepreneurial environment. tor from Stockholm’s NeuroVive Pharma- eliminating the harsh side effects of older, He stayed on as an adviser to Gilead during ceutical. Cyclophilin inhibitors were also less effective therapies. a transitional period but was already start- explored in HCV, but Sofia points out that That quick cure made Sovaldi the biggest ing to think about a hepatitis B-focused OCB-030 is structurally very different than drug launch in history. Approved late in start-up. the molecules tested in HCV. Moreover, it 2013, Sovaldi brought in more than $10 bil- In mid-2012, Sofia, along with three has proven more potent in preclinical stud- lion for Gilead last year. other Pharmasset veterans, launched On- ies, he says. Now, Sofia has set his sights on the hepa- Core in Doylestown, Pa. The idea was to Other acquisitions include Enantigen titis B virus, another serious liver infection. build on their collective experience in HCV Therapeutics, another Doylestown-based He’s spent the past three years thinking to tackle HBV. start-up. It brought surface antigen secre- about what a cure for HBV might look like They knew that a cure for HBV would tion inhibitors, meant to tackle viral im- and, through a biotech firm he cofounded likely require a combination of drugs, just mune control, and capsid assembly inhibi- called OnCore Biopharma, acquiring prom- as the HCV cure did. And as for HCV, an tors, which target the viral reservoir. ising molecules. effective HBV treatment would need to OnCore also licensed several projects In January, OnCore from the Blumberg Insti- was acquired by Canada’s tute, a nonprofit research Tekmira Pharmaceuticals, TACKLING HEPATITIS B institute associated with which has its own HBV The combined pipeline of Tekmira and OnCore addresses the the Hepatitis B Founda- activities. Now at the multiple ways the hepatitis B virus survives in its host tion that is also located in helm of Tekmira’s R&D Doylestown. Two of those operation and in charge of VIRUS SURVIVAL TARGET projects focus on other VIRAL IMMUNE VIRAL a broad new drug pipeline, CANDIDATE REPLICATION CONTROL RESERVOIR DEVELOPMENT STAGE ways to attack the viral Sofia faces the challenge TKM-HBV x x Phase I reservoir, which is com- of repeating the success of OCB-030 x x IND-enabling studies posed of covalently closed Sovaldi. No pressure. CYT003 x IND-enabling studies circular DNA. Despite an available Capsid assembly inhibitors x Lead optimization “We believe strongly vaccine, the hepatitis B Surface antigen secretion that cccDNA is going to be virus chronically infects inhibitor x Lead optimization the solution to the cure, cccDNA formation inhibitor x Lead optimization some 240 million people ultimately, and we’ve put a STING agonist x Research around the world, almost cccDNA epigenetic modifier x Research lot of effort into this area,” twice the number who Sofia says. have HCV, according to IND = investigational new drug. cccDNA= covalently closed circular DNA. SOURCE: Te k m i ra Armed with a portfolio the World Health Organi- of molecules spanning

CEN.ACS.ORG 18 MAY 4, 2015 multiple mechanisms of action, OnCore’s managers intended to take the company public. They had gone so far as to compile the lengthy document required by the Se- curities & Exchange Commission, known as the S-1, before selling stock to the public and were in the midst of a road show to potential investors. Then Tekmira came calling. Tekmira was one of several companies that OnCore had been chatting with as it explored the potential for treating HBV with small interfering RNA. “It became clear when we talked to the people at Tek- mira that they had a very similar vision,” Sofia says. And because there was minimal overlap between Tekmira’s siRNA capabili- ties and compounds and OnCore’s small- molecule ones, “it became a natural fit.”

IN JANUARY, Tekmira and OnCore agreed to merge in a deal that gave OnCore share- holders 50% of Tekmira’s stock. At the time, the combined company was valued at $750 million. For Tekmira, the deal was transforma- tive. Although several other companies— including Gilead, Alnylam, and Arrowhead Research—are working on HBV treatments, industry watchers were happy to see a broad collection of assets under one roof. News of the merger sent Tekmira’s stock price up roughly 50%. When the transaction closed in March, Sofia became the chief scientific officer of Tekmira. He is now part of a team of roughly 120 people—about twice the size of Pharmasset during most of its existence, al- though still a far cry from a big pharma firm. Meanwhile, Tekmira’s siRNA-based HBV treatment, TKM-HBV, is already in a Phase I trial, and a Phase I trial of OCB-030 is planned for the second half of this year. If all goes well, analysts expect the company to start its first study combining TKM-HBV and OCB-030 next year. As trials begin to roll out, Sofia expects to see a transformation in how HBV is treated. “HBV is where HCV was about 12 years ago,” he says. “You can imagine a stepwise scenar- io like you saw in HCV where new therapies Submit your research to ACS Central Science— improve cure rates, then reduce duration a new, multidisciplinary, open access journal that of therapy, and ultimately get to the point presents groundbreaking advances in the world where we all want to be—an all-oral, combi- of chemistry and beyond. nation therapy with a high cure rate.” Sofia would like to be a part of find- ing that cure. Still, he knows he’s the rare ACSPublications medicinal chemist to have even one cure Most Trusted. Most Cited. Most Read. under his belt. “Sofosbuvir is a hard act to follow,” he says. ◾

CEN.ACS.ORG 19 MAY 4, 2015 BUSINESS

production have been met with skepticism CHASING CHEAP SILICON by industry analysts. “While fluidized-bed reactor systems WACKER CHEMIE hopes a novel production technology are a proven technology, at this point, poly- silicon manufacturers have not proven that it is developing can make it more competitive it leads to sustainable success in the mar- ket,” says Mark Barineau, a solar analyst with Lux Research, a market research firm. IF YOU HAVE LUNCH with Rudolf represents a major opportunity, Wacker Industry experts estimate that the Staudigl, the measured chief executive of says. The firm has named its technology granular process could reduce the cost Wacker Chemie, the Bavarian chemical the granular float-zone process, or GFZ. of making polysilicon to $10 to $15 per kg producer, don’t expect him to be a barrel of In the standard float-zone pro- laughs. cess, Siemens polysilicon is melted

It’s been a tough time for Wacker’s with an induction coil and grown WACKER polysilicon business, as well as Siltronic, into a monocrystalline ingot. The the firm’s silicon wafer subsidiary. Already crystal is highly pure because surface faced with high capital and energy costs, tension allows it to “float” around a Wacker and its competitors have had to support rod without the need for a swallow a huge dip in selling prices for containing vessel that might cause polysilicon and silicon wafers after the contamination. A drawback is the market became swamped with supply. high cost of running the Siemens Ask Staudigl to name his favorite in- process. GFZ avoids this by using house R&D project, though, and he will lower-cost polysilicon granules, crack a smile. That’s because it is a novel according to Hans-Peter Bortner, approach for making certain semiconduc- director of silanes production for tor wafers that could lead to significant Wacker. cost savings. Staudigl is optimistic. “It’s a Yet several technical challenges very exciting project,” he tells C&EN. must be overcome for the GFZ tech- The standard approach to manufactur- nology to meet its targets for quality ing high-purity polycrystalline silicon is the and cost-effectiveness, Wacker says. LOW-COST OPPORTUNITY compared with $12 Siemens process. Developed by the Ger- Although the fluidized-bed approach A silicon ingot produced to $20 per kg for the man firm Siemens in the 1950s, it involves is economical, the polysilicon gran- by Wacker with the latest iterations of process known as GFZ. heating thin silicon rods in large vacuum ules it yields have higher levels of the Siemens process. chambers in the presence of hydrogen and impurities than do the chunks from Although granular trichlorosilane at 1,100 °C for several days. the Siemens process. A focus of processes may be the When the reaction is complete, the bell- Wacker’s development of GFZ is reducing future, right now the Siemens process “is shaped chamber lid is lifted to reveal sever- these impurities in the final product. much more reliable and bankable than al tons of high-purity silicon coating the sil- Wacker has begun operating a develop- fluidized-bed reactors,” says Richard M. icon rods. After being smashed ment reactor at its biggest poly- Winegarner, president of Sage Concepts, a into chunks, this polysilicon silicon plant, in Burghausen, consulting firm with expertise in the poly- is then melted and grown into “Wacker’s Germany, dedicated to testing silicon sector. large monocrystalline ingots biggest the manufacture of float-zone A more immediate concern for Wacker, using a method named after its ingots from granular polysili- Winegarner points out, is the domination inventor, the Polish scientist problem is con. “We are working on getting of the silicon sector by Chinese firms po- Jan Czochralski. The ingots are not being the costs down and on reaching tentially propped up and protected by their sliced to form the silicon wafers the needed product quality,” government. “Wacker’s biggest problem is used in semiconductors and Chinese.” Bortner says. not being Chinese,” he says. Even if Wacker solar panels. Although Wacker says it were to step up its activities relating to In recent years, Wacker and some of its expects GFZ to become a commercial suc- granular polysilicon, “I don’t think Siltron- competitors have independently devel- cess, the firm has to date been reluctant to ic is ever going to be a huge moneymaker,” oped fluidized-bed deposition techniques manufacture granular polysilicon at large Winegarner says. as a potentially lower-cost alternative to scale. Indeed, the silicon wafer market is such the Siemens process. Instead of polysilicon a tough place to do business that Staudigl chunks, it creates polysilicon granules. POLYSILICON GRANULES may yield recently initiated a review to determine Now Wacker is seeking to use granular not only a cheaper route for GFZ but also whether Wacker should sell Siltronic. polysilicon in a novel approach to make so- cheaper commercial production of solar Although GFZ may yet prove to be the called float-zone silicon wafers, which are panels. But recent claims by other leading exciting commercial technology Staudigl used to make high-end electronic switches polysilicon producers—including REC Sili- hopes it will be, for Wacker it may be one rather than solar panels and semiconduc- con, SunEdison , and GCL-Poly —that they technology that delivers too little, too tors. The market is growing rapidly and are on track to scale up granular polysilicon late. — ALEX SCOTT

CEN.ACS.ORG 20 MAY 4, 2015 DISCOVER

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American Chemical Society GOVERNMENT & POLICY CONCENTRATES

BILL WOULD LET STATES INDUSTRY ASKS FDA TO DITCH OPT OUT OF CO2 CUTS CHANGES TO DRUG-LABEL RULES States could duck upcoming EPA regulation of carbon dioxide emissions from power Trade groups representing the branded and generic pharmaceutical in- plants under a bill the House Energy & dustries are urging the Food & Drug Administration to scrap its proposal Commerce Committee adopted last week. to change the way generic drug labels are updated to reflect safety risks. The measure, H.R. 2042, would put EPA’s FDA has proposed to allow generic drug manufacturers to independently rule for curbing CO2 from existing power plants on hold until federal courts have fin- modify labels if they become aware of new safety issues that might pose a ished a review of EPA’s authority to address risk for consumers. Currently, generic drug makers must wait until either climate change under the Clean Air Act. FDA requires an update to the drug’s labeling or the original manufacturer “We’re not repealing the regulation,” says decides to change its label. At that point, the generic drug must bear the Rep. Ed Whitfield (R-Ky.), the bill’s spon- same label as the reference drug. But the proposed rule creates a scenar- sor. “Let’s let the courts render a decision.” io “where potentially conflicting information from multiple manufacturers The legislation would allow governors to for single medicines could be widespread,” causing confusion and put- opt out of the EPA rule, expected to be out ting patient safety at risk, says the Generic Pharmaceutical Association in July, if they determine the regulation (GPhA). Instead, GPhA and the branded drug lobby, the Pharmaceutical would threaten electricity reliability or have Research & Manufacturers of America , say FDA should determine wheth- “adverse effects” on ratepayers. Governors er new warnings on drug labels are needed and, if so, require all manufac- would be required to consult with state turers to make the changes. — GH regulators, environmental agencies, and others in making the determination. Demo- crats are strongly opposed to the bill. “This is a thinly veiled excuse to do nothing about the agency says. The American Academy of consumption is flat, coal use is declining, climate change,” says Rep. Bobby L. Rush Pediatrics and the American Dental Associa- and natural gas and renewables are surging. (D-Ill.). The committee passed the measure tion issued statements in support of the up- The U.S. is emerging as the world’s leading 28–23, clearing the way for the full House to dated guidelines. Excess fluoride in drinking producer of oil and natural gas combined, vote on, and likely pass, the bill.— SG water can cause dental fluorosis, a condition according to the report. — SG that can cause noticeable white stains or pits on the teeth. —JM FLUORIDE LEVELS IN MEASURE TAKES AIM WATER LOWERED AT ‘PATENT TROLLS’ ENERGY INFRASTRUCTURE For the first time in more than 50 years, the NEEDS UPGRADES Reviving a push for reform that stalled last Department of Health & Human Services year, members of the Senate Judiciary Com- has changed the recommended concen- Obsolescence of the electric grid and mittee introduced bipartisan legislation tration of fluoride in drinking water. New natural gas and oil infrastructure warrants last week that would crack down on “pat- guidance from the U.S. Public Health new investment to ensure resilience and ent trolls.” The bill is aimed at combating Service recommends 0.7 mg/L rather than reliability, the Energy Department says in what some businesses say is growing abuse the previous range of 0.7 mg/L to 1.2 mg/L. its “Quadrennial Energy Review.” Accord- of litigation by companies that buy patent The change affects more than 12,000 com- ing to the report, released last week, about portfolios for the sole purpose of trying to munities that add fluoride to their drinking 50% of natural gas pipelines were built extract fees and financial settlements from water supply to prevent dental cavities. The between 1950 and 1970, and surges in gas alleged infringers. Sen. Chuck Grassley recommendation updates and replaces the volume necessitate between $2.6 billion (R-Iowa), committee chairman and one agency’s 1962 Drinking Water Standards for and $3.5 billion in new investment by 2030. of the bill’s cosponsors, says the panel will community water fluoridation. The change The report focuses on the role of transport, vote on the measure by late May. The leg-

comes as data suggest that fluoride is now SHUTTERSTOCK storage, and distribution infrastructure islation was quickly praised by pro-reform available to Americans from in a rapidly changing energy landscape. groups, including the recently formed several sources, including Although much of this infrastructure is United for Patent Reform, whose members toothpastes, mouth rinses, privately held, the federal government include Google, Facebook, telecom giants, and dietary supplements, owns significant portions, including and retail lobbying groups. The Biotech- transmission lines and storage facili- nology Industry Organization, a trade as- The federal ties, and has a role in regulating what it sociation, says the bill includes “noticeable government does not own. Climate-related chang- improvements” over an anti-patent-troll has tightened es such as sea-level rise, thawing per- measure (H.R. 9) pending in the House of the levels of fluoride in mafrost, and extreme weather are Representatives. But the group says the drinking water already affecting this infrastructure Senate proposal still needs to better protect for the first time in many regions, the report adds. the ability of biotech companies to assert since 1962. In addition, domestic petroleum their intellectual property rights. —GH

CEN.ACS.ORG 22 MAY 4, 2015 GOVERNMENT & POLICY

COAL POWER plant pollution each PacifiCorp’s Jim year, according to the Bridger Plant in Wyoming burns agency. JIM URQUHART/REUTERS JIM 8 million to The high court 9 million tons of is expected to issue coal annually. a ruling in the case, Michigan v. EPA, by the end of June. The deci- sion could set an important precedent on whether the agency needs to consider the potential costs before it decides whether regulation is warranted under the Clean Air Act. When Congress amended that federal law in 1990, it directed EPA to aggressively control emissions of mercury and more than 180 other hazardous air pollutants. The statute says the agency “shall regulate” the major sources of these pollutants where it is “appropriate and necessary.” EPA concluded that it was both appropri- ate and necessary to regulate mercury from power plants based in part on studies of HIGH COURT WEIGHS Americans who rely on fish for a substantial part of their diet. Mercury pollution from these facilities may be making fish unsafe EPA MERCURY RULE for human consumption in 65% of the U.S. waters that receive atmospheric fallout of Justices will determine whether agency must the metal, according to the agency. consider both costs and public health in deciding EPA also says the acid gases and micro- scopic particles emitted by electric utilities AIR POLLUTION whether to regulate can cause asthma, lung problems, and heart GLENN HESS, C&EN WASHINGTON disease. In December 2011, the agency finalized new standards requiring about 1,400 gen- THE ENVIRONMENTAL Protection Agen- latory question of whether it is appropriate erating units at 600 power plants, most of cy’s first-ever regulation limiting releases to regulate,” the plaintiffs’ brief asserts. which burn coal and are in the South and of mercury and other toxic air pollution EPA’s Mercury & Air Toxics Standards, upper Midwest, to install high-tech scrub- from power plants is facing its final legal which began to take effect in April, require bers and other devices to remove the pol- hurdle. The Supreme Court is considering power plants to reduce their emissions of lutants. At the time, the Energy Information whether EPA went too far when it final- mercury by 90%. The pollution control Administration reported that 64% of the ized a rule to protect public health that the technology needed to strip mercury out of facilities had already installed pollution agency estimates will cost electric utilities the plants’ releases to the air will also reduce control equipment to comply with the new and their customers almost $10 billion per emissions of acid gases such as hydrogen standards. year. chloride by 88% and particulate-forming “By affirming these vital emission stan- Mercury is a potent neurotoxin; tiny doses sulfur dioxide by 41%—providing what the dards, the Supreme Court would also help can harm children’s development and pose agency calls “cobenefits.” EPA believes that level the playing field for the two-thirds of risks for fetuses of pregnant women. Coal- the regulation will produce between $37 bil- coal-fired plants that have already upgraded burning power plants, which are the largest lion and $90 billion in public health cost their plants,” says Graham McCahan, a staff source of mercury in the U.S., are facing a savings per year. attorney at the Environmental Defense series of EPA regulations that require owners That means lower health care costs for Fund, an advocacy organization. to invest in pollution controls or shut down downwind residents, fewer lost workdays, aging facilities. and a reduction in early deaths. Up to 11,000 BUT INDUSTRY GROUPS such as the The justices are evaluating industry and people die prematurely as a result of power National Mining Association and nearly state arguments that EPA violated the Clean Air Act by failing to consider the potential financial burden before it decided to issue “EPA has expressly refused to those emission limits. “Congress did not in- consider the cost of its regulation, tend for EPA to act with deliberate indiffer- ence to cost when answering the basic regu- which will result in rate increases.”

CEN.ACS.ORG 23 MAY 4, 2015 GOVERNMENT & POLICY

two dozen states assert that judgment to determine whether EPA’s regulation amounts EMISSIONS A large portion of U.S. air pollution comes regulation is appropriate. “Is there to a prohibitively expensive from power plants. any case in all of our decisions “overreach” by the Obama where we have said even though Administration. Acid gases 77% there was no instruction to con- They argue that the benefits sider costs, EPA is required to con- 62% of controlling the utility emis- Arsenic sider costs?” she asked. sions of mercury amount to Sulfur dioxide 60% Sotomayor added that all the only $4 million to $6 million Supreme Court has to do is find Mercury 50% annually and that the rest of the that EPA made a “plausible read- benefits come from the reduc- Nickel 28% ing” of the Clean Air Act to rule in tion of particulate pollution, Chromium 22% the agency’s favor. which is regulated by other EPA But several members of the programs. Nitrogen Court’s conservative majority oxides 13% A three-judge panel of the criticized EPA’s position. Justice U.S. Court of Appeals for the Antonin Scalia, who authored the District of Columbia Circuit 2001 decision on costs under the upheld the new standards last Clean Air Act, called the mercury year. But 21 states, the mining regulation “outrageously expen- association, and the Utility sive.” He said the decision not to Air Regulatory Group, a util- conduct a cost-benefit analysis SOURCE: EPA ity lobbying group, petitioned early in the rule-making process the Supreme Court to hear the was “a silly way” to interpret the case. They contend that the Clean Air Act not mention costs anywhere in its text. statutory language. required EPA to take into account compli- The Court’s four-member liberal wing Chief Justice John G. Roberts Jr. said ance costs when it was deciding whether largely voiced support for EPA’s approach. the rule’s estimated $9.6 billion annual to regulate toxic air emissions from power For instance, Justice Elena Kagan said the price tag “raises the red flag” because only a plants. argument that the agency must consider “tiny proportion” of the calculated benefits “EPA has expressly refused to consider costs despite the law’s silence on the is- are attributable to a reduction in mercury the cost of its regulation, which will result sue is at odds with a 2001 Supreme Court emissions. in rate increases for citizens across the decision. “I’m just questioning the legitimacy” country, and threatens the reliability of the In that case, Whitman v. American Truck- of counting cobenefits from reductions of electricity grid by forcing the closure of ing Associations, the justices unanimously particulates that are regulated under other many power plants,” says Michigan Attor- agreed that EPA is prohibited from consid- sections of the Clean Air Act, Roberts said. ney General William D. Schuette. ering cost when setting national ambient He described that approach as an “end run” Supporters of the rule hope the justices air quality standards for ground-level ozone around the statutory language. will lean toward giving EPA deference to and other common air pollutants. interpret the Clean Air Act as it did when it Congress has often explicitly required ON THE OTHER HAND, Justice Anthony decided to consider only public health risks EPA to consider the cost of its regulations M. Kennedy, who has often been the swing in determining that the rule was necessary. but said nothing to that effect in the Clean vote on the nine-justice Court, expressed EPA has said it took the cost of technology Air Act’s provision on power plant emis- sympathy for both sides of the issue. He into account at a later stage in the regula- sions, Kagan said. “Congress knows how said the word “appropriate” is ambiguous, tory process when it crafted the specific to require consideration of costs,” she re- which suggests Congress gave EPA some emission standards. marked. “To get from silence to this notion leeway. of a requirement seems to be a pretty big But Kennedy also seemed skeptical of DURING ARGUMENTS before the high jump.” the agency’s decision to wait and consider court last month, U.S. Solicitor General Justices Ruth Bader Ginsburg and Sonia cost later in the regulatory process, when Donald B. Verrilli Jr. defended the agency. M. Sotomayor both signaled that the Court it set the exact emission standards. Once He called it “certainly appropriate for should defer to an agency’s interpreta- EPA decided that power plants should be EPA to list power plants for regulation tion of an ambiguous statute as long as the regulated, “at that point, the game is over,” based solely on health and environmen- agency’s reading is reasonable. he said. tal hazards.” The relevant section of the Ginsburg said Congress often directs Although the justices were clearly di- Clean Air Act, Verrilli pointed out, does an “expert agency,” such as EPA, to use its vided over the mercury rule, the Court has sided with EPA in recent decisions. Last year, the justices upheld a rule that curbs Up to 11,000 people die prematurely air pollution that drifts across state lines, deferring to EPA’s reading of the clean air as a result of power plant pollution law. The Court also largely validated the agency’s plan to regulate major sources of each year, according to EPA. greenhouse gas emissions. ◾

CEN.ACS.ORG 24 MAY 4, 2015 C&EN TALKS WITH

MICHAEL E. ROGERS Medicinal chemist has overseen much of NIH’S CHEMISTRY RESEARCH since 1993 ANDREA WIDENER , C&EN WASHINGTON

FOR MICHAEL E. ROGERS, working at the Chemist Mike I was there, people National Institutes of Health is the chem- Rogers is retired thought I did.” ist’s equivalent to being a kid with a job in a from NIH. While on detail in candy store. Congress, he became “If you have interests in biomedical sci- more interested in the research programs ence, I can’t think of any better place to at NIH, so when he came back to the agency

be,” he says. WIDENER/C&EN ANDREA he joined NIGMS. He became acting direc- That is what kept Rogers , 69, at NIH for tor in 1993 of what became the Division almost 35 years. Through the decades, his of Pharmacology, Physiology & Biological career has spanned from peer review to Chemistry, which funds approximately 60% legislative affairs to creating chemistry re- of NIH chemistry research, he says. search programs. That has put Rogers in a position to For the past 20 years, Rogers oversaw make vital investments at the intersection the majority of chemistry research funded of biology and chemistry. One of the most through NIH as director of the Division important may have been creating grants of Pharmacology, Physiology & Biologi- to train chemists in biological concepts, he cal Chemistry in the National Institute of says. General Medical Sciences (NIGMS). “My In the early 1990s, “if you were a chem- whole professional life has been combining ist and you wanted to get some training chemistry and biology,” explains Rogers, in biology, it wasn’t necessarily that well who retired on May 1. accepted,” Rogers remembers. The program, he says, “provided Growing up in rural Georgia, Rogers didn’t expect to become validation for a lot of people who wanted to work at the chemis- a chemist. His parents didn’t finish grammar school, and he was try-biology interface,” an area that is booming now. the first person in his family to graduate from high school. But Looking back, one the most exciting times to work at NIH was an aunt encouraged him to attend community college. There, he in the late 1990s, when the agency’s budget doubled. “We were gravitated toward chemistry, inspired by his experience in a high able to start some programs that we wouldn’t have been able to school chemistry class. do otherwise,” he says. One example is the agency’s so-called Rogers went on to earn a bachelor’s degree in chemistry from glue grants, which fund large-scale team research projects in Berry College in Georgia. As he neared graduation, he heard a talk many fields, including chemistry. given by some pharmaceutical chemists from the University of The financial situation now is significantly different. “You Mississippi. “I liked chemistry, but the idea of being able to use have more people competing for the same money, and the money that knowledge to make drugs? I was totally snowed,” doesn’t goes as far,” he says. he remembers. One of Rogers’s biggest concerns is the pressure So off he went to graduate school at the University “If you have this puts on young scientists, who feel like they have to of Mississippi in the department of medicinal chemis- interests in make a major breakthrough to get a job and research try, which he followed with a postdoc at NIH in 1972. funding. “The thrill of discovery itself gets lost,” he After that, Rogers took a faculty position at Virginia biomedical says. Commonwealth University. When it became clear he science, I That thrill is what has kept Rogers engaged through wasn’t going to get tenure, he returned in 1980 to NIH, can’t think the years. He sees the human microbiome as an up-and- where he remained until last week. of any better coming research area for chemists. “We know relatively Rogers started out overseeing grant review in what p l a c e t o b e .” little about the chemical communication that goes on was then called the Division of Research Grants. He between gut bacteria and the body,” he says. “That of- founded the bioorganic and natural products chemistry study fers a lot of opportunities for chemists.” section and chose its first members. “I always considered it one He has also been leading a push into quantitative and systems of the great wonders of the world that they let me do that,” he pharmacology research, which looks at the body as a system and says. how a drug interacts broadly within it. “That is the one area I re- A few years later, Rogers took a six-month assignment working ally hate to give up,” he says. on the Senate’s Labor & Human Resources Committee, which Rogers says what he’ll miss the most, besides the people at was then led by Sen. Edward Kennedy (D-Mass.). “That was a NIH, is that amazing sense of discovery. “If you are following sci- blast,” he says, pointing out a picture of himself and Kennedy ence, it is like following your favorite TV drama because there is hanging in his office. “I didn’t have any power. But just because always a new development.” ◾

CEN.ACS.ORG 25 MAY 4, 2015 SCIENCE & TECHNOLOGY CONCENTRATES

GROWING THE THINNEST GIANT PORPHYRIN GOES OF SEMICONDUCTORS BIG ON AROMATICITY For supermodels and semiconductors, it seems that thin is always in. As electronics By increasing the number of pyrrole makers continue to squeeze more com- groups in a porphyrin ring ponents into increasingly smaller spaces, they’re on the lookout for materials that from the usual four to 12, an can achieve the ultimate in small—atomic- international team of chem- scale electronic devices. Now, Jiwoong ists has succeeded in making Park and colleagues at Cornell University the largest aromatic report an advance toward realizing such molecule known to date materials. They’ve grown sheets of the ( Chem. Eur. J. 2015, DOI: transition-metal dichalcogenides MoS 2 10.1002/chem.201500650 ). and WS 2 that are only three atoms thick, Expanding the realm of but stretch over an area of about 10 sq in aromaticity is nothing new (Nature 2015, DOI: 10.1038/nature14417 ). for Dongho Kim of South Korea’s Park’s team made the monolayer sheets Yonsei University and Atsuhiro This tetraprotonated via a new metal-organic chemical vapor Osuka of Japan’s Kyoto University. Their groups dodecaphyrin, with 50 π electrons, has set a new deposition process, using Mo(CO) 6 or have been collaborating for a few years to make big record for aromaticity. W(CO)6 as the transition-metal source and aromatic porphyrins in the quest to study anion and diethylsulfide as the sulfur source. They metal binding and electrochromic effects. In their latest effort, the researchers used a tripyrrole building block to construct a [52π]dodecaphyrin, a porphyrin ring consisting of a dozen connected pyr- role groups and adorned with pentafluorophenyl groups. This conjugated

molecule has 52 π electrons and is nonaromatic—it doesn’t obey Hückel’s CHEM. EUR. J. rule of possessing 4n + 2 π electrons. To meet the criterion, the team oxi- dized the molecule with a benzoquinone to form a [50π]dodecaphyrin, which bests the former aromaticity record holder, a [46π]decaphyrin the groups made last year. Subsequently protonating the [50π]dodecaphyrin using methanesulfonic acid helped flatten the molecule and improve its added hydrogen gas MoS 2 and WS2 to remove any built- can now be grown electron delocalization, thereby enhancing its aromaticity further.— SR NATURE up carbonaceous as atomically thin films with a deposits. The result- measured area of ing films were of suffi- 10 sq in. ncomms7939). The researchers made the of the solvent and the substrate. Thus, for cient quality to make nanolasers from a gold nanoparticle ar- a given substrate and nanoparticle array, field-effect transis- ray surrounded by a liquid gain material changing the solvent changes the emission tors. The method does have some limita- composed of dye molecules dissolved in wavelength. By integrating the nanoparticle tions: It takes about 26 hours and requires organic solvent. The nanolaser is activated array in a microfluidic device, the research- temperatures of 550 °C. Even so, Park and by pumping it optically with an external ers were able to change the solvent and the coworkers note that the technique is “a light source. The resulting emission wave- lasing wavelength in real time. For example, step toward the realization of atomically length is dictated by the refractive indexes a nanolaser made from the dye IR-140 in thin integrated circuitry” and could find dimethyl sulfoxide and a nanoparticle array use in the fabrication of flexible electron- on fused silica emitted light at 862 nm. By By varying the composition of a liquid ics, photovoltaics, and displays.— BH medium (colored plugs at inlet) flowing switching to benzyl alcohol, the same de- over a gold nanoparticle array, the laser vice lased at 891 nm.— CHA light emitted by this tiny device can be SWITCHING SOLVENTS quickly tuned over a range of wavelengths. TUNES NANOLASERS METHYLATED ADENINE FUNCTION DETERMINED Nanolasers, which could be used to supply light to lab-on-a-chip devices, have been The methylated genomic base N 6-methyl- made with solid lasing, or “gain,” materi- adenine (6mA) has been found in the als. But the output of these light sources genomes of bacteria and small eukaryotic couldn’t be tuned after fabrication. Teri W. organisms such as ciliates and algae but Odom of Northwestern University and co- not in higher organisms, and its function workers have now made plasmonic nanola- in eukaryotes has been unknown. Now, sers that are tunable from 858 to 913 nm in researchers have found it in two higher or-

real time (Nat. Commun. 2015, DOI: 10.1038/ NAT. COMMUN.ganisms and have determined a functional

CEN.ACS.ORG 26 MAY 4, 2015 SCIENCE & TECHNOLOGY CONCENTRATES

role in algae. Eric Lieberman Greer and inside the battery. The other battery simply the authors say it’s too early to make defini- Yang Shi of Harvard Medical School and exploded, blowing off the battery cap and tive predictions, they see this finding as be- coworkers found 6mA in worms; Hailin ejecting molten material.— MJ ing useful for wound-healing applications. Wang and Dahua Chen of the Chinese Though the team studied only one death Academy of Sciences, Beijing, and col- cycle, “one of our aims is to test how many leagues discovered it in fruit flies; and a SULFIDE MINERAL generations of zombies can be extracted group led by Chuan He of the University REDUCES CO2 from a single dose,” Avnir says. “In principle, of Chicago studied its role in algae (Cell if the silver is not washed away, then many 2015, DOIs: 10.1016/j.cell.2015.04.005 , An iron sulfide mineral that forms in deep generations are expected.”— EKW 10.1016/j.cell.2015.04.018 , and 10.1016/j. sea hydrothermal vents can convert CO 2 cell.2015.04.010). He and coworkers found and hydrogen to small bioorganic molecule that 6mA is widely distributed between precursors such as methanol and formic, NANOSHEETS CATALYZE DNA-packaging units in the algal genome, acetic, and pyruvic acid (Chem. Commun. NITROGEN FIXATION suggesting that it regulates gene expres- 2015, DOI: 10.1039/c5cc02078f ). The dis- sion. Epigenetics expert Thomas Carell of covery, by Nora H. de Leeuw of University A research team in China has invented a Ludwig Maximilian University of Munich College London and colleagues, provides a light-harvesting layered semiconductor comments that the findings emphasize potential lead for developing environmen- nanosheet that could one day significantly that modified bases have important regula- tally friendly catalytic syntheses of plastics tory functions and are more widespread and fuels. It also lends credence to the than was previously thought. — SB theory that prebiotic chemistry flourished in the mineral- and carbon-rich alkaline environment that typifies some hydrother- PEERING INSIDE AN mal vents. Scientists have known that this EXPLODING BATTERY mineral, greigite (Fe 3S 4 ), resembles the fer- redoxin center of the CO dehydrogenase By coupling high-speed X-ray tomography enzyme. In previous studies, researchers and thermal imaging methods, researchers showed that greigite can convert CO 2 to have demonstrated that events occurring gaseous CH4 and CO. However, to serve as prebiotic precursors, small organics must A layered BiOBr A new imaging be in solution. So the team performed ex- photocatalyst reduce the energy re- method reveals in real periments at various pH values and found binds N2 in oxygen quired for chemically time events inside a that an alkaline environment was key to vacancy sites as reducing nitrogen to commercial Li-ion part of a low- battery (roughly 18 mm producing methanol and the other small energy nitrogen- ammonia. Convert-

in diameter) that cause organics that are solution-based at atmo- fixing process. ing N2 to NH3 via SOC. CHEM. AM. J. it to explode and eject spheric pressure and room temperature. the iron-catalyzed molten material. And by using computational methods, the Haber-Bosch process group explained the dependence of the is one of the most important industrial inside a lithium-ion bat- methanol and formic acid formation mech- chemical reactions. But splitting N 2 and tery as it heats up and anisms on alkaline conditions. — EKW preparing hydrogen via steam reforming of explodes can be imaged in high resolution methane at high temperature and pressure and real time (Nat. Commun. 2015, DOI: make it one of the most energy-intensive 10.1038/ncomms7924 ). The three-dimen- ‘ZOMBIE BACTERIA’ KILL processes. Lizhi Zhang of Central China

NAT. COMMUN.sional imaging method provides a novel USING SILVER BULLETS Normal University and coworkers designed way to investigate heat-induced damage a layered BiOBr catalyst with oxygen vacan- to internal structures of Li-ion batteries, In a newly discovered mechanism, after cies that is ideal for binding N 2 molecules. which could lead to improved battery safety. an antimicrobial silver agent kills bacteria, When the researchers shine visible light on Standard analytical methods are limited the agent is then capable of moving on to the nanosheet surface the semiconductor to scrutinizing the internal components of kill still more bacteria ( Sci. Rep. 2015, DOI: generates electrons to reduce adsorbed failed batteries only after the events that 10.1038/srep09555 ). Dubbed the “zombies N 2 while at the same time it oxidizes water + caused the failure have run their course. So effect” by David Avnir of Hebrew University solvent molecules to generate H and O2 . a team led by Paul R. Shearing of University of Jerusalem and colleagues, the extended Overall, the process couples nitrogen and College London devised the tomography toxicity of silver nitrate stems both from the hydrogen to make NH 3 at room tempera- method and used it to study two standard ability of the silver to form nanoparticles ture and atmospheric pressure with better types of commercial Li-ion batteries as they and remain active after it kills and from its efficiency than previously reported semi- heated the battery shells to roughly 250 °C. subsequent release from the corpses of bac- conductor systems ( J. Am. Chem. Soc. 2015, One battery, strengthened with an inter- teria. The group first used silver nitrate to kill DOI: 10.1021/jacs.5b03105 ). “Although pho- nal support, remained largely intact until Pseudomonas aeruginosa. They then separated tocatalytic reduction is unlikely to replace chemical reactions triggered thermal run- and cleaned the dead bacteria and added the Haber-Bosch process at present,” the away. The internal temperature then spiked them to a live culture of the same bacteria, researchers write, “this study might open up above 1,000 °C, melting copper structures killing more than 99.99% of them. Although a new vista.” — SR

CEN.ACS.ORG 27 MAY 4, 2015 SCIENCE & TECHNOLOGY from the SCENEs

A selection of stories from C&EN’s six online TOPICAL NEWS CHANNELS

FROM THE NANO SCENE fibers make better electrical connections are much smaller and thus capable of CARBON NANOTUBES with brain tissue in rats, which may im- targeting brain regions more precisely— MAKE GOOD BRAIN prove prosthetic devices and deep-brain delivered current for DBS as effectively ELECTRODES stimulation (DBS) therapies for disorders as the metal electrodes. The flexibility of such as Parkinson’s disease. Chemist Mat- the nanotube electrodes offered another Electrodes made from carbon nanotube teo Pasquali and neural engineer Caleb Ke- benefit: After six weeks of implantation, fibers can both stimulate and receive mere of Rice University implanted 12-µm- nanotube fibers did not trigger inflamma- signals from the brain without causing in- diameter nanotube fibers in rats with tion in the brain tissue, unlike the more flammation (ACS Nano 2015, DOI: 10.1021/ Parkinson’s-like symptoms and compared rigid metal electrodes. The team is now de- acsnano.5b01060). Compared with con- them with platinum electrodes coated with signing arrays of the electrodes to interact ventional metal electrodes, the nanotube iridium. The nanotube electrodes—which simultaneously with multiple brain areas.

FROM THE MATERIALS SCENE FROM THE ENVIRONMENTAL SCENE SHAPE-SHIFTING PLASTIC BAGS CUT DOWN SUBSTANCE ON MARSH WILDLIFE STAYS SOFT ACS MACRO LETT. MACRO ACS Plastic bags do not simply harm individual Shape-memory polymers can be bent birds and mammals when the animals get tan- or twisted into a new configuration, gled in the trash, the bags also can affect entire which they’ll hold until some stimu- communities of wildlife, according to a new lus—such as heat—reverts them to study ( Environ. Sci. Technol. 2015, DOI: 10.1021/ their original shape. But the same acs.est.5b00277). Marine ecologist Dannielle material properties that help fix these Senga Green of Trinity College, in Ireland, and polymers into a new shape also tend to colleagues examined plastic litter’s effects make them inflexible, limiting their use on a marsh near Dublin, in which sediments in biomedical applications. Now, using serve as home to algae and a variety of inver- a simple technique, researchers have tebrates such as worms, crabs, and snails. The made a soft, rubbery shape-memory team pinned down conventional high-density elastomer by combining two different plastic polymers (ACS Macro Lett. 2015, DOI: bags and biodegrad- 10.1021/acsmacrolett.5b00106). Pat- able bags made rick T. Mather of Syracuse University from cornstarch and his group chose a commercially in sediment plots available thermoplastic polyurethane in the marsh. After that stays soft at room temperature Researchers made an object out of a nine weeks, the re- and poly(ε-caprolactone), which re- shape-memory elastomer composite searchers found that GREEN SENGA DANNIELLE mains crystalline until heated above (top) then heated and fixed it into a oxygen levels in sedi- 56 ºC. The second polymer helps the twisted shape (center). When they ments under both material “remember” its shape at room heated it again, it untwisted itself into types of bags were far its original shape (bottom). temperature. The researchers elec- lower than in bagless A plastic bag litters trospun separate solutions of the two plots. The mud a marsh near polymers onto a metal cylinder, form- the final product, a dense film. By heat- beneath bags had Dublin. ing a composite fiber mat. They then ing, twisting, and cooling the film, the one-sixth as many compressed and heated the mat into researchers could reshape the material. animals. And algae may have suffered because chlorophyll concentrations were half as high. Green says the results indicate that plastic The SCENE news channels are brought to you by C&EN’s Journal bags, even biodegradable ones, could harm News & Community group. To subscribe to weekly e-mail newsletters marsh ecosystems, but she warns it’s unclear from any of our six SCENEs, go to http://cenm.ag/newsletters. how they might affect other types of habitats.

CEN.ACS.ORG 28 MAY 4, 2015 SCIENCE & TECHNOLOGY

normuscone and other musk molecules. Then they expressed a human musk THE HEADY MUSK OF receptor called OR5AN1 in human em- bryonic kidney cells, a common cellular SCIENTIFIC DEBATE system that has been used to study the mechanisms for sight and taste, and eval- uated the response of the musk receptor VIBRATIONAL THEORY New data rebut of olfaction to their array of musk odorants. SARAH EVERTS , C&EN BERLIN The researchers found that the musk receptor did not respond any differently when presented with deuterated and

HOW EXACTLY OUR sense of smell SHUTTERSTOCK nondeuterated versions of normuscone, works is one of the most important, muscone, and other musk odorants unanswered questions in sensory (Proc. Natl. Acad. Sci. USA 2015, DOI: science. It’s also a question that 10.1073/pnas.1503054112 ). has resulted in an acrimoni- “Even though I like underdog ous, nearly two-decade-long hypotheses, this is by far the controversy. strongest evidence refuting On one side of the battle the vibrational hypothesis are a majority of sensory to date,” says blogger and scientists who argue that drug discovery chemist our odorant receptors Derek Lowe , who has long detect specific scent followed the olfaction molecules on the basis debate on his blog, In of their shapes and the Pipeline. “They ran a chemical properties. lot of good experiments On the other side are with a lot of care. The vi- a handful of scientists brational hypothesis had who posit that an odor- a lot of chances to rear ant receptor detects an its head, and it didn’t.” odor molecule’s vibra- “It’s frankly a sledge- tional frequencies. hammer to Turin’s A new study, led by vibrational hypothesis,” Eric Block , chemistry says Kenneth S. Suslick , professor at the University a sensory scientist at the at Albany, SUNY, takes aim University of Illinois, Urba- at the vibrational theory of na-Champaign, who has ar- olfaction and finds no evi- gued for some time against the dence that olfactory receptors vibrational olfaction model. distinguish vibrational states of AIR OF MYSTERY molecules. The precise mechanism IN RESPONSE, Turin calls the The vibrational theory was first of how we smell remains new study “very interesting,” but proposed about a century ago, but its a mystery. he does not think it makes a success- modern-day proponent is biophysicist ful case against vibrational theory. Luca Turin , a visiting professor at Ulm In particular, Turin believes that the University, in Germany. Block’s new study musk receptor studied by Block and col- challenges a 2013 paper by Turin and his it does alter its vibrational frequencies. leagues may not correspond to the one colleagues that had given the vibrational The take-home message of Turin’s 2013 he studied in the noses of human test field a boost ( PLOS One, DOI: 10.1371/ paper was this: If subjects who journal.pone.0055780). Turin’s 2013 pa- humans are able O O differentiated per reported that human subjects could to smell the dif- deuterated and identify a difference in odor between ference between nondeuter- deuterated and nondeuterated musk deuterated and ated versions of molecules, such as normuscone. Human nondeuter- normuscone. Muscone Normuscone subjects thought the deuterated versions ated forms of “Their entire smelled burnt or roasted. the same odor- paper rests on These experiments supported the ant, then vibration could have a role in the fact that the musk receptor that they vibrational model of olfaction because olfaction. are studying is the same one that the hu- deuteration doesn’t significantly alter In the new study, Block and his col- mans were using to perceive the musk in the chemical structure of a molecule, yet leagues prepared deuterated versions of the PLOS paper. Humans have multiple

CEN.ACS.ORG 29 MAY 4, 2015 SCIENCE & TECHNOLOGY

BIRTHDAY SHOT NASA unveiled this Hubble musk receptors,” Turin says. “We just don’t image of a giant know if it was the right receptor.” cluster of hot, new stars for the Block says if Turin can point him to an- telescope’s 25th other human musk receptor—one that is anniversary. involved in vibrational olfaction—he’d be happy to study it. Block adds that his team screened a full panel of all the human odor receptors, and of these, only OR5AN1 “ro- bustly responded to musk.” TEAM 2 SCIENCE ESA/STSCI/WESTERLUND

ANOTHER OF TURIN’S objections is that Block and colleagues did their experiments with cells in a dish rather than within whole organisms. He argues that expressing an TEAM (STSCI/AURA)/ HERITAGE NOTA/NASA/ESA/HUBBLE A. olfactory receptor in human embryonic kidney cells doesn’t adequately reconsti- tute the complex nature of olfaction and is not biologically significant. Leslie B. Vosshall , a sensory scientist at Rockefeller University, doesn’t ac- cept that argument because scientists have successfully used human embry- onic kidney cells to study rhodopsin and adrenaline receptors, which are related to olfactory receptors. “Embryonic kidney HUBBLE’S 25TH cells are not identical to the cells in the nose,” she says. “But if you are looking BIRTHDAY BASH at receptors, it’s the best system in the world.” World celebrates the spacecraft that’s revealed details Turin thinks that neither side of the de- CHEMISTRY OF THE UNIVERSE bate has totally satisfactory data. On the about the structure and one hand, “what we have are behavioral ELIZABETH K. WILSON , C&EN WEST COAST NEWS BUREAU tests on flies and on humans,” he says. And on the other hand, there are receptors expressed in cells. IT WAS 1992, and the Hubble Space Tele- cosmological game-changing discoveries One way to move the field forward scope had been in orbit around Earth just that have cemented Hubble’s place as one would be to solve the crystal structure of two years. of the technological marvels of the modern an olfactory receptor. Scientists have yet A group of astronomers trained Hubble’s space age. to do so because the receptors are mem- high-resolution spectrograph on an ancient Hubble was launched 25 years ago on brane proteins that can’t be expressed in star 100 light-years away and found some- April 24, 1990. No spacecraft’s birthday has large amounts, Suslick says. thing never before seen in a star: boron. been so elaborately feted: In recent weeks, “Smell is a fascinating, beguiling sense, This element’s emissions lie in the more than 100 events have been held in the the more so because we don’t really un- ultraviolet part of the electromagnetic U.S. alone, including the unveiling of an of- derstand how it works,” notes Tim Jacob, spectrum—in a range only observable from ficial Hubble 25th anniversary image at the emeritus professor in sensory science at outside Earth’s atmosphere and only de- Newseum in Washington, D.C. Cardiff University, in Wales. “It is a shame tectable by Hubble at the time. Hubble team members and officials cel- that the quest to find a solution to the The star, estimated to be about 15 billion ebrated Friday, April 24, at a private party puzzle of smell, has been distracted by years old, was expected to contain only the at the Smithsonian Institution’s National the attempt just to refute the opposing elements believed to have formed during Air & Space Museum; the next day, the theory.” the Big Bang: primarily hydrogen, helium, museum threw another Hubble party for “These scientists have paid Luca Turin and lithium. But this discovery got astrono- the public. From April 20–26, Times Square the compliment of taking the theory seri- mers wondering whether boron, a heavier in New York City was alive with celestial ously,” Lowe says. “When his hypothesis element, could have been formed during Hubble images, broadcast from the area’s came out a lot of people just brushed the Big Bang as well. It’s a question that iconic Toshiba Vision dual LED screens. it aside as a stupid, annoying idea. And still hasn’t been answered. “Hubble has changed the way scientists that’s not appropriate.” However, he says, That early, startling, and chemical-based view the universe, and it’s captured the Turin “is the one proposing the more finding is just one in a lengthy parade of imagination of the public,” Amber Straughn, unusual hypothesis, so he’s the one who has to bring the extraordinary evidence to To see more of Hubble’s chemical hits, go to support it.” ◾ MORE ONLINE http://cenm.ag/hubble25yr .

CEN.ACS.ORG 30 MAY 4, 2015 NASA LOOKING OUTWARD The Hubble telescope orbits Earth. an astrophysicist at the National Webb will focus on studying Aeronautics & Space Administra- infrared wavelengths, which eas- tion, said during a panel discus- ily penetrate dust and gas that sion on Hubble’s 25 years at the mask objects in space. The tele- Space Telescope Science Institute scope will also be able to more (STScI) in Baltimore. completely study the chemical “It’s been a great 25 years,” composition of atmospheres on Ken Sembach, interim director planets outside the solar system. at STScI, said at the conference. Many organic compounds have “Hubble is doing science now that characteristic infrared spectra. was never before envisioned.” “The exoplanet community is very excited about the Webb HUBBLE’S VISUAL STUNNERS telescope,” said Jacob L. Bean , have included images of events close to was sending back vivid, crisp images. an astronomy and astrophysics professor home—the impact of comet Shoemaker- The telescope has undergone four ser- at the University of Chicago. With Webb’s Levy 9 on Jupiter in 1994—as well as those vicing missions, including the 1993 repair. improved precision and infrared focus, as- of objects at the edges of the universe, in- Traveling via space shuttle, astronauts tronomers hope to be able to find exoplan- cluding galaxies that formed only 400 mil- have journeyed to the spacecraft to replace ets that are truly analogous to Earth. lion years after the Big Bang. Hubble found old cameras and gyroscopes with new ones. Hubble may still have a chance to break proof of the exotic phenomenon of gravita- The final repair mission was in 2009. new ground during its final years, espe- tional lensing, in which dense objects can Hubble will keep taking images and data cially if it overlaps with the first years of the bend light from an object behind it. Hubble until its instruments give out, NASA says. Webb telescope: Because Hubble’s instru- also provided evidence for the acceleration Scientists are hoping it will last until at ments observe primarily visible and ultra- of the expansion of the universe. least 2020. violet wavelengths, it could complement Many of the breathtaking images of qua- In October 2018, NASA is set to launch Webb’s infrared observations. sars, interstellar dust formations, and col- the first of a next generation of space According to STScI’s Sembach, “The liding galaxies have become so iconic that telescopes, the James Webb Space Tele- combination of these two observatories it might seem that Hubble’s primary func- scope. Much more powerful than Hubble, will be very powerful, scientifically.” ◾ tion has been to explore the macrostruc- ture and grand cosmology of the universe. But Hubble is also, at its heart, a chemist. HUBBLE’S GREATEST CHEMICAL HITS A full 50% of Hubble’s observations have Although the spacecraft is best known for its spectacular galactic images, many been made with its spectrometers, which of its discoveries have been chemical in nature. Here, we highlight a few of those, lead to chemical discoveries, says Douglas accompanied by artists’ renderings. Duncan, one of the astronomers who made the boron discovery. “Few people know ◀ 1992 H ubble detects the element boron in an that.” Duncan is now in the department of ancient star, causing astronomers to wonder whether astrophysical and planetary sciences at the boron formed during the Big Bang. In 2013, Hubble University of Colorado, Boulder, and is also confirmed that this star is the oldest yet detected. director of Fiske Planetarium. Although they don’t always lend them- selves to spectacular images, Hubble’s chemical discoveries have been some of the most intriguing: the discoveries of sodium, methane, and water in the atmospheres of FIELD/NASA/ESA SUMMERS/A. F. exoplanets, water in the remnants of a dead star, and a complex organic soup in a solar- NASA/ESA/JPL/CALTECH system-forming protoplan- etary disk. Hubble’s technological history will also be remem- bered. The most famous event, perhaps, was the dis- ▲ 2014 H ubble detects water in the atmosphere of covery soon after the space- G. BACON/STSCI/AVL an exoplanet. Most exoplanets discovered so far have been large, often many times larger than Jupiter. This craft’s launch of an optical exoplanet is the smallest on which a molecule has flaw in its Wide Field & ever been detected. Planetary Camera. In 1993, astronauts were able to fit ◀ 2001 Hubble makes the first discovery of an the mirror with corrective atmosphere—composed of sodium—on an exoplanet optics, and soon Hubble outside the solar system.

CEN.ACS.ORG 31 MAY 4, 2015 SCIENCE & TECHNOLOGY

VISIT ÅLAND ÅLAND VISIT winemakers did so with concentrated grape juice sugar instead of cane sugar, which was also available then. The researchers came to this conclusion because they detected fur- fural derivatives in the ancient champagne, which are produced during the Maillard re- action as grape juice is slowly heated. Initially, the team of scientists thought that the ship ferrying the champagne must have been en route to Russia, where there SHIPWRECKED FIZZ was a predilection for sweet wine. But ac- In 2010, divers found cording to historical documents, the nearly this cache of 170-year- old champagne in the 150 g/L of sugar in the shipwrecked cham- Baltic Sea. pagne corresponds to German and French sweetness preferences of that era. Russians of the 19th century wanted even sweeter wine: vino that contained 30% sugar, a 170-YEAR-OLD whopping 300 g/L, Waterhouse says. JEANDET AND HIS GROUP also discov- CHAMPAGNE ANALYZED ered three orders of magnitude more salt in the preserved bottles than in modern Chemical analysis of SHIPWRECKED BUBBLY reveals vintages. At first the team suspected that there must be some seawater contamina- secrets of 19th-century French winemaking tion, Jeandet says. But the researchers ruled out this possibility by comparing the ratio of bromine and chloride ions in the A 170-YEAR-OLD STASH of perfectly pre- been in operation since 1772, the research- bubbly with ratios of those ions found in served champagne taken from a shipwreck ers were able to compare the 170-year-old the Baltic Sea. off the coast of Finland has brought to light champagne with modern incarnations Instead, the salt was probably added by an array of curious facts about past wine- from the champagne maker. The discov- the champagne producer, albeit not inten- making practices. Chemical analysis of the ery, and consequent chemical analysis on tionally. Champagne makers used to add vintage sparkling wine revealed particularly three of the shipwrecked bottles, was an gelatin to keep wine from going cloudy, high levels of sugar and salt compared with “unequaled opportunity in ferreting out Jeandet says, and salt was added to the gel- modern-day champagne, as well as the aspects of the evolution of sparkling wine atin to keep it stable. Today, gelatin is used presence of unexpected metals, likely intro- production that’s been unavailable in the as a clarifying agent, but the substance is duced by 19th-century wine preservation written record,” says Ronald S. Jackson, a now much purer and, thus, less salty, Wa- and storage methods ( Proc. Natl. Acad. Sci. wine science scholar at Brock University, terhouse says. USA 2015, DOI: 10.1073/pnas.1500783112 ). in Ontario. The shipwrecked champagne also con- The champagne also tasted “fabulous, One of the most interesting aspects of tained unusually high levels of iron, lead, with hints of tobacco,” says Philippe Jean- the recovered champagne is that the sugar copper, and arsenic compared with mod- det, a champagne chemistry expert at the levels are “spectacularly high—higher than ern vintages. Arsenic and copper sulfate University of Reims Champagne-Ardenne, most dessert wines produced today,” let found in the century-old fizz likely origi- in France, who led the team of researchers, alone champagne, comments Andrew L. nated from antiquated pesticides used to and who sampled 100 µL of the golden liq- Waterhouse, a wine scientist at the Uni- kill fungus. Meanwhile the iron and lead uid. That drop of vintage champagne “was versity of California, Davis. Current cham- probably came from storage containers. probably one of the best wines I’ve tasted pagne comes in two main styles: “very dry,” If the idea of aging wine underwater in my life,” he says. which contains little residual sugar, and an sounds like the basis for a new industry, Jeandet isn’t the only person to have even drier “brut.” Both contain two orders regulators in the U.S. don’t agree. In March, sampled the shipwrecked bubbly. In 2010, of magnitude less sugar then than the ship- the Alcohol & Tobacco Tax & Trade Bureau divers who discovered the 168 bottles in wrecked champagne. “The idea of making issued a warning about the niche indus- the cool, dark—and preservative—waters champagne with so much sugar” today, try of ocean-aging, called “aquaoir.” The of the Baltic Sea popped a cork when they Waterhouse says—“a winemaker would regulatory body worries that the industry’s hit dry land and realized they were most just laugh at you.” wares may be adulterated or contaminated likely drinking century-old champagne, In fact, the levels of sugar measured in by seawater pollutants, such as gasoline, Jeandet notes. Although the bottles no the ancient champagne were higher than heavy metals, drug residues, pesticides, longer had labels, the corks were engraved those found naturally in grape juice. This and effluent from sewage treatment plants. with the name of a French champagne finding suggests that winemakers in the 19th Aquaoir enthusiasts will certainly point house, Ponsardin. century probably boosted levels artificially. to this champagne’s successful 170-year Because Veuve Clicquot Ponsardin has Jeandet and his team believe that these storage in rebuttal.— SARAH EVERTS

CEN.ACS.ORG 32 MAY 4, 2015 ACS COMMENT Speaking For More Than 158,000 Members JOHN ADAMS , DISTRICT V DIRECTOR AND CHAIR , COMMITTEE ON PUBLIC AFFAIRS & PUBLIC RELATIONS

AS A MEMBER OF the American Chemical of the society’s public policy priorities. other tiers of investment, the lowest level Society Board of Directors, I am often asked Our positions fall into four broad cat- consisting of issues that are monitored for why our society is not doing anything about egories: fostering innovation through targets of opportunity. Furthermore, ACS (take your pick here) research funding, sci- research and technology, strengthen- is an active leader in the Washington, D.C., ence education, climate, or any of a dozen ing science education and the scientific science and technology policy community, other issues. Once I explain what we in fact workforce, advancing science through working across sectors in coalition with the are doing on the issue, the openness, and promoting science and engineering, education, and member often follows with science and sustainability business communities on a wide range of a question about how these in public policy. topics. things get decided. For many issues, more Now, how do we actually advance these ACS is a large, multifacet- detail is required to make positions? That effort is a shared respon- ed organization. Most of our us effective advocates sibility among members, governance, and members are very familiar for chemistry and its professional staff in Washington, D.C. with those specific programs practitioners. That detail Our staff, housed in the ACS Office of that provide them with di- PHOTOGRAPHY PETER CUTTS is provided in ACS policy Public Affairs (OPA), provides us a wide rect professional benefit, but statements. There are cur- range of services. In consultation with few are experts on all ACS rently 24 such statements PA&PR, staff translate policy positions into offerings. One important that can be found at www. letters to Congress, into talking points for activity that is noticed by few acs.org/policy. Several ACS ACS members to use when visiting elected members is fulfillment of committees routinely work officials, and sometimes into legislative our national charter respon- with the board to draft language that works its way into congres- sibility to provide science ACS is an active these positions, and PA&PR sional bills. They also provide nonpartisan and engineering advice to leader in the gives final approval (C&EN, briefings on the application of science and the government and to ad- Washington, March 2, page 36). technology to public policy issues through vocate the advancement of Last year, PA&PR, acting the ACS Science & the Congress Project. chemistry. D.C. science and on the recommendations of The sum of all of these efforts is a biparti- The members of the ACS technology policy seven ACS committees and san policy agenda that allows us to work Board, and particularly the community. one technical division, ad- effectively with both political parties no members of the Board Com- opted 11 policy statements . matter who is in charge of Congress, the mittee on Public Affairs & The committee process Administration, or statehouses. Public Relations (PA&PR), allowed hundreds of ACS To the surprise of some of our members, spend substantial time in this arena because members to contribute to ACS position our staff also includes registered lobby- we are charged by the ACS constitution development. Through coverage in C&EN ists who work directly with Congress to with approving “any statement purporting and on the Web, all ACS members were in- advance our positions. Like most U.S. not- to express the position of the Society on vited to offer input to the process. for-profit organizations, we are allowed to any public matter.” As you might imagine, spend a small fraction of our annual budget speaking for an organization of more than WITH SO MANY POSITIONS on such a to advance policy positions through pro- 158,000 members with varied interests is no wide range of matters (most of which are fessional lobbying, and OPA provides that small task. Fortunately, we have consider- important to some sector of ACS or the service as part of a comprehensive ACS able help in fulfilling these responsibilities. practice of our science), priorities need advocacy program. So how do we determine what ACS will to be set to keep the focus on those issues Here, though, is the most important part say on the broad array of issues covered by where advocacy effort from members and of my message to members. All this ACS U.S. science-related policy at the national staff will yield maximum benefit. These policy infrastructure is pointless unless our and state levels? priorities are set by the board, working members are involved. Therefore, let me First and foremost, we work with a with staff to evaluate the likelihood of leg- end by sharing this advice: In order for our wide range of members, committees, islative or other policy action and to assess common interests to gain currency and the and divisions to follow the issues and the society’s ability to have an impact on power to influence, your elected officials get advice on what our positions might the outcomes. need to hear from you. Yes, I mean YOU! be. Every other year, we include 15 ACS This process allows us to put the lion’s committees in the development of a one- share of our resources on the highest prior- Views expressed on this page are those of page document that lays out an overview ities in a top tier while differentiating three the author and not necessarily those of ACS.

CEN.ACS.ORG 33 MAY 4, 2015 AWARDS

AIC GOLD MEDAL TO Stubbe will present a lecture on Sept. 24 than 25 clinical candidates for the preven- JACQUELINE BARTON at Johns Hopkins. tion of thrombosis, the treatment of stroke, and therapy for viral infections such as HIV. Jacqueline Barton, Arthur & Marian Hanisch Memorial Professor of Chemistry JAMES COWAN RECEIVES and chair of the division of chemistry and 2015 MORLEY MEDAL INORGANIC chemical engineering NANOSCIENCE AWARD at California Institute The ACS Cleveland Section has named TO STANISLAUS WONG of Technology, is the re- James A. Cowan as the winner of its 2015 cipient of the 2015 AIC Edward W. Morley Medal. Cowan, who is Stanislaus S. Wong, a professor of chem- Gold Medal, presented the Melvin S. Newman Professor of Chem- istry at Stony Brook University, SUNY, who by the Chemical Heri- istry & Biochemistry at Ohio State Univer- holds a joint appointment at Brookhaven tage Foundation (CHF) sity, will receive the prize during a confer- National Laboratory, is the winner of the and the American Insti- ence and dinner hosted by the Cleveland 2015 Inorganic Nanoscience Award, pre- tute of Chemists. Section at John Carroll University in Uni- sented by the ACS Division of Inorganic The medal recogniz- versity Heights, Ohio, on May 20. Chemistry to honor excellence in research. es service to the science of chemistry and to The Morley Medal recognizes significant The award is sponsored by the University of the profession of chemist or chemical engi- contributions to chemistry through achieve- South Carolina’s NanoCenter. neer in the U.S. It will be presented on May ments in research, teaching, engineering, Wong’s research focuses on inorganic 15 during CHF’s Heritage Day festivities. research administration, and public service, nanomaterials. His efforts include probing Barton pioneered the application of as well as outstanding the covalent surface chemistry of carbon transition-metal complexes to probe rec- service to humanity or nanotubes as well as studying the synthe- ognition and reactions of double-helical to industrial progress sis, characterization, and energy-related DNA. She has designed chiral metal com- in the Cleveland region. applications of novel noncarbonaceous, plexes that recognize nucleic acid sites with Cowan’s research metal-based nanostructures. specificities rivaling DNA-binding proteins. focuses on catalytic Wong will receive a plaque and $3,000 at These synthetic transition-metal complexes and physicochemical the fall ACS national meeting in Boston. have been useful in elucidating fundamental properties of iron co- chemical principles that govern the recogni- factors and their bio- tion of nucleic acids, in developing lumines- synthesis, cellular traf- PUBLICATION WINS cent and photochemical reagents as new ficking, and regulation of metal cofactors; INAUGURAL ENERGY diagnostic tools, and in laying a foundation the development of catalytic metallodrugs; & FUELS AWARD for the design of novel chemotherapeutics. and the biological chemistry underlying She has received numerous awards, in- the role of metals in disease. The publication “Hydrothermal Liquefac- cluding the 2015 ACS Priestley Medal and tion and Gasification of Nannochloropsis sp.” 2010 National Medal of Science. (2010, DOI: 10.1021/ef100203u), by Phillip PORTOGHESE Savage of Pennsylvania State University, is LECTURESHIP TO the inaugural winner of the Energy & Fuels 2015 REMSEN AWARD NICHOLAS MEANWELL Joint Award for Excellence in Publication. TO JOANNE STUBBE The award is presented by the journal Nicholas Meanwell, executive director Energy & Fuels and the ACS Division of JoAnne Stubbe, Professor of of discovery chemistry at Bristol-Myers Energy & Fuels to honor an outstanding Chemistry and professor of biology at Squibb, is the recipient of the Philip S. article published in the journal. Savage will Massachusetts Institute of Technology, is Portoghese Medicinal Chemistry Lecture- give a talk at the ACS national meeting in the recipient of the ship. The lectureship is named in honor of Boston in August. 2015 Remsen Award, the former editor-in-chief of the Journal of presented by ACS’s Medicinal Chemistry and is administered by Maryland Section. It is Portoghese and the ACS Division of Me- COMP ANNOUNCES named after Ira Rem- dicinal Chemistry. 2015 AWARDS sen, Johns Hopkins The lectureship honors the contribu- The ACS Division of Computers in Chem- University’s first chem- tions of an individual who has had a major istry presented several awards during the istry professor and impact on medicinal chemistry research. It spring 2015 ACS national meeting in Denver. second president. consists of a $3,000 honorarium, a plaque, The OpenEye Outstanding Junior Fac- Stubbe’s research and $1,500 to cover travel expenses to the ulty Award in Computational Chemistry group has helped reveal the mechanisms of fall ACS national meeting in Boston to helps new faculty members gain visibility some of nature’s most complex and impor- present the lecture. within the COMP community. The win- tant enzymes. Some of her group’s most Meanwell has led drug discovery pro- ners are Arindam Chakraborty, Syracuse noted work defines how nature harnesses grams in the cardiovascular, neuroscience, University; Rhiju Das, Stanford University; the reactivity of free radicals to carry out and virology therapeutic areas. This work Konrad Patkowski, Auburn University; difficult chemistry with great specificity. has resulted in the advancement of more and Jordan Schmidt, University of Wis-

CEN.ACS.ORG 34 MAY 4, 2015 consin, Madison. Each winner received a chemistry and of molecular and computa- CALL FOR BUCK-WHITNEY $1,000 prize. tional biology at the University of Southern AWARD NOMINATIONS The Chemical Computing Group Excel- California, is the winner of the David Y. lence Award for Graduate Students, co- Gin New Investigator Award, which ac- The ACS Eastern New York Section is so- sponsored by CCG and COMP, recognizes knowledges and encourages outstanding liciting nominations for the Buck-Whitney outstanding research performance by a contributions to research in carbohydrate Award. The award, named after late section graduate student in computational chem- chemistry by scientists in the first seven members Johannes S. Buck and Willis R. istry. The recipients are Vivek Bharadwaj, years of their independent career. Whitney, recognizes original work in either Colorado School of Mines; Feizhi Ding, Katsunori Tanaka, associate chief sci- experimental or theoretical aspects of pure University of Washington; Nan Li, North entist at Japan’s RIKEN, is the winner of or applied chemistry. Carolina State University; Greg Medders, the Horace S. Isbell Award, which acknowl- Nominees must have made outstanding University of California, San Diego; and edges excellence in and promise of contin- contributions to chemistry and be resi- Heather Wiebe, Simon Fraser University. ued quality of contribution to research in dents of North America. Chemists whose The winners each received $1,150 and a copy carbohydrate chemistry. work has not yet received a significant of CCG’s MOE (Molecular Operating Envi- national or international award, and whose ronment) software with a one-year license. careers would be advanced by such recog- PETROLEUM RESEARCH nition, are especially encouraged to apply. FUND ANNOUNCES The award includes a medal and citation, a CARB PRESENTS GRANT RECIPIENTS $1,000 honorarium, and travel expenses to DIVISION AWARDS deliver an award address to the section. The ACS Petroleum Research Fund has Nominations should include the nomi- The ACS Division of Carbohydrate Chem- announced the recipients of research nee’s name, affiliation, and accomplishments istry presented its 2015 division awards grants in 2014. The ACS Board of Directors in chemistry. Mail nominations by June 1 to during the 2015 spring ACS national meet- approved 192 grants with a total value of Michael Hagerman, Buck-Whitney Award ing in Denver. $19 million for advanced scientific educa- Committee Chair, Department of Chemis- Arland Hotchkiss, lead scientist at the tion and fundamental research related to try, Union College, Schenectady, NY 12308, U.S. Department of Agriculture’s Agricul- petroleum and other fossil fuels. The list of or e-mail to [email protected]. tural Research Service, is the winner of the grantees is available online at acsprf.org by Melville L. Wolfrom Award, which acknowl- clicking on “About ACS PRF.” Additional edges outstanding service to the division information on grant programs and up- LINDA WANG compiles this section. and to the field of carbohydrate chemistry. coming proposal submission dates is also Announcements of awards may be sent to Matthew Pratt, assistant professor of available on the site. [email protected].

MEETINGS Joint Southeastern/Southwest Regional Meeting Call For Papers The call for papers for the 2015 Joint a quiz bowl competition involving SMACS Characterization & Applications,” “Recent Southeastern/Southwest Regional Meet- (Student Members of ACS) clubs from Advances in Chemical Physics,” “Student- ing has been issued. The meeting will take the two regions. Centered Learning in the Chemistry Class- place on Nov. 4–7 at the Memphis Cook Symposia for the meeting include “Bio- room & Laboratory,” “The Chemical Indus- Convention Center and the Sheraton medical Materials,” “Biomolecular Crystal- try in the South: Future Careers, Directions Memphis Downtown Hotel, in Tennessee. lography,” “Biomolecular NMR,” “Biorelat- & Challenges,” “The Interface of Ab Initio Details, including names and contact ed Polymers: Synthesis & Applications,” Computational & Bioorganic Chemistry,” information for program and session “Chemical Genetics,” “Computational “The Interface of Chemistry with Art & Ar- chairs, can be found on the meeting Studies of Protein Function,” “DNA-Modify- chaeometry,” and “Tomorrow’s Therapeu- website at 2015sermacs-swrm. ing Enzymes,” “Drug Discovery Tech- tics: Natural Products.” com. The final program sum- nologies,” “Entrepreneur’s Tool Kit: General technical sessions will cover mary will be published in C&EN Resources & True Stories,” “Envi- analytical, biological, computational, inor- in the fall; the online program ronmental Analysis,” “Frontiers in ganic, organic, and physical chemistry. In will be available on Sept. 28. Nucleic Acids Chemistry,” “Gold addition, the meeting will include a plena- Special events at the meet- Nanoparticles in Nanomedicine,” ry lecture, five undergraduate symposia, ing will include a barbecue “Intrinsically Disordered Proteins: and 13 poster sessions. dinner, regional awards luncheon, From Physical Chemistry to Biol- ACS’s Meeting Abstracts Programming exposition and graduate school fair, ogy,” “Ion-Conducting Polymers,” “Mass System (MAPS) opened on April 27 for and a program for high school chemistry Spectrometry,” “Materials for Alternative submission of abstracts. Please visit either teachers. The undergraduate program Energy Applications,” “Mobile Analysis,” the symposium website or MAPS at maps. will include a luncheon, demonstration “Multiscale Modeling of Macromolecular acs.org to submit an abstract. Abstracts session, green chemistry workshop, and Systems,” “Nanomaterials: Synthesis, are due by 11:59 PM EDT on Aug. 10. BRAND USA © MEMPHIS CONVENTION & VISITORS BUREAU VISITORS & CONVENTION MEMPHIS © USA BRAND

CEN.ACS.ORG 35 MAY 4, 2015 ACS career tips

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CEN.ACS.ORG 39 MAY 4, 2015

59 PM newscripts CHEMICAL ARTISTRY, MICROWAVE OVEN ASTRONOMY, SCIENTIFIC MUSICALITY

eronica Berns faced a common graduate student challenge: how V to explain what you’re doing to a nonchemist family member or friend. Her solution? A COMIC BOOK. “I tried to come up with something that would convey the ideas and purpose and motiva- tion without using technical jargon,” says Berns, who got her Ph.D. from the University of Wisconsin, Madison, last year and now works as a research scientist for chemical c o m p a n y U O P. Berns’s artistry describes her research in Daniel C. Fredrickson ’s lab to understand the three-dimensional structures that form when metals are mixed together. Astronomer confounder: “In crystals, atoms pack orderly and Microwave ovens tightly, like oranges in a grocery store opened midcycle tories in Australia display,” Berns writes in the comic. “Crystals produce perytons. and Switzer- are organized and repeat themselves. In land. Because every direction. Predictably. This allows us perytons typically occurred on weekdays to summarize a whole big crystal in one tiny during of ce hours, the scientists were SHUTTERSTOCK box: the unit cell.” pretty sure they were of human She told her lab origin. But what precisely was the group about the PERYTONS’ PROVENANCE? project when it The key lay in linking the pery- was about halfway tons with other signals around 2.3 done. Fredrickson BERNS VERONICA to 2.5 gigahertz, a frequency at became a big which microwave ovens are known proponent and to emit. That led to a set of tests convinced her to spearheaded by Emily Petrof of include it as the Swinburne University of Technol- fi nal chapter in her ogy, in Australia, that involved heat- thesis, she tells ing mugs of water in microwaves Newscripts. at that country’s CSIRO Parkes In January, she Observatory . launched a Kick- But perytons didn’t appear starter campaign when scientists just ran the ovens. to print the comic Communicator: It wasn’t until someone opened a book on its own. Berns on her microwave door before the timer ran out She hoped to raise book cover. that the source of perytons was conclusively $5,965 and did that identifi ed (arXiv: 1504.02165 [astro-ph.IM] ). within a week; as of C&EN press time, she was up to $14,400. She’s received mes- ast year, Newscripts featured the sages from people saying things like, “My “Song of the Chemist,” a chemically daughter’s interested in chemistry and I L themed ditty by 19th-century com- don’t know anything about it, maybe we can poser George F. Root ( C&EN, May 5, 2014, read this together,” she says. “Those have page 40 ). Lew Naylor of Apple Environmen- been the most rewarding e-mails to get,” tal Services and Indiana’s Goshen College Berns notes. “I’m happy to be able to be the requested the words and music, then instigator for that conversation that they worked with students—a male quartet and wanted to have.” videographer—to create a DELIGHTFUL MUSIC VIDEO. To view it, go to cenm.ag/ hile Berns worked to explain her chemistsong . science in common language, W astronomers were working to discover a common source for perytons. JYLLIAN KEMSLEY wrote this week’s column. Perytons are transient, 250-millisecond Please send comments and suggestions to bursts of radio signals detected at observa- [email protected].

CEN.ACS.ORG 40 MAY 4, 2015 ONLY YOU KNOW WHAT MATTERS MOST We’re here to help

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Advances in Spectroscopy And Materials Analysis

2 Publisher's Note 9 Detection of Methylmalonic Acid (MMA) in Plasma Using Kevin Davies, Ph.D. Hydrophilic Interaction Liquid Chromatography (HILIC) Coupled with Mass Spectrometry (MS) or Tandem Mass Spectrometry 3 Light on my Mind Maricar Dube and Patrik Appelblad Vicki Mountain, Ph.D. EMD Millipore

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1 PUBLISHER'S NOTE

This C&EN Supplements is produced by C&EN, the fl agship magazine of the American Chemical Society. American Chemical Society 1155 16th Street, NW Materials World Washington, DC 20036 ELCOME TO THE second C&EN Supplement for 2015. This supplement is (202-872-4600; 800-227-5558) devoted to “Advances in Spectroscopy and Materials Analysis,” and features Wa selection of application notes from leading instrumentation companies that C&EN Supplements Management are pushing the boundaries of spectroscopy analysis. Many of these tools were on Kevin A. Davies display at recent conferences including Pittcon in New Orleans and the ACS National Publisher, C&EN Meeting in Denver. Bibiana Campos Seijo These vendor contributions are complemented by an editorial selection of abstracts Editor-in-Chief, C&EN from ten of the most impactful research articles relevant to this fi eld, as seen over the Stephanie Holland past 12 months in the peer-reviewed journal Analytical Chemistry, published by the Manager, Advertising Sales and Marketing American Chemical Society. Renee Zerby Manager, Digital Production & Imaging Thanks to our contributing editor, Victoria Mountain, who shepherded this supple- Joseph B. Davis, Jr. ment to fruition with the help of C&EN’s digital production manager Renee Zerby and Lead Digital Production Associate her staff. Our thanks also to Analytical Chemistry managing editor Antonella Mazur for Krystal E. King gathering the Top Ten list and to the companies that contributed to this C&EN Supple- Lead Digital Production Associate ment. Marielyn Cobero We have an exciting series of supplements in store for the rest of this year, including Digital Production Associate a special edition on technology in BRICS countries and an in-depth issue looking at Cesar Sosa Digital Production Associate the Top 20 Drugs in the Pipeline later this summer. If you are interested in participating in future C&EN supplements or any of our print, digital or lead-generation media offerings, please visit the C&EN media site—http:// ACS Management acsmediakit.org/—and don’t hesitate to contact me. Thomas M. Connelly, Jr. Best wishes, CEO & Executive Director Brian D. Crawford President, ACS Publications

To advertise in C&EN Media Group products, contact Stephanie Holland at (202) 872-4536 ([email protected]) or go to CENMediaKit.org Kevin Davies, PhD Publisher, C&EN Email: [email protected] Cover design by Marielyn Cobero Image: Reprinted with permission from AAAS

@ 2015 American Chemical Society

For the record: The editorial content in this supplement was created without direct involvement of C&EN reporters or editors.

2 C&EN SUPPLEMENT • MAY 2015 ADVANCES IN SPECTROSCOPY AND MATERIALS ANALYSIS LIGHT ON MY MIND Vicki Mountain, Ph.D.

REETINGS, AND welcome to this latest special supplement to Chemical & Engineering News magazine. The prominent theme of this issue is Gspectroscopy, a technique founded on the study of visible light, although it has since expanded to encompass other forms of radiative energy. The connection to light is fortuitous, especially for those of us in the Northeast who endured a long, arduous winter and are now delighting in the arrival of spring, and the increasing hours of daylight this season brings.

This year more than others, throughout the world, light has who currently face the dual challenges of fi rst fi nding the cancer been at the forefront of popular science news, grabbing the cells—an especially diffi cult task for invasive cancers—and attention of the general public. In March 2015, a solar eclipse, second, making sure they have removed all the cancerous tissue where the moon passes between the Earth and the Sun, was knowing that if they leave these cells behind, tumors may regrow observed throughout Europe, as well as in parts of Northern and impact the patients life. The tool, developed by a team of and Eastern Asia, and Northern and Western Africa. In some Canadian researchers from Montréal Polytechnique and McGill places a total solar eclipse could be seen, turning day into night University, is a handheld contact Raman spectroscopy probe that by blocking all direct sunlight for a time. detects cancer cells locally in live human brains, during surgery. The greatest celebration of light this year, however, is taking In the C&EN report, Petrecca, one of the team leaders, notes place across the globe: 2015 has been designated the Interna- that the next step is to run clinical trials to demonstrate that the tional Year of Light by the United Nations Educational, Scien- Raman technique can improve surgery outcomes, and that such tifi c, and Cultural Organization, UNESCO. A series of events is a trial will begin soon. We will be certain to revisit this story as the planned throughout the year with the intention of raising public results of the clinical trial are revealed. awareness and understanding of the importance of light and Not surprisingly, Raman spectroscopy is used in several optical technologies to people throughout the world. More infor- of the articles featured in our latest selection of Top 10 papers mation on the International Year of Light can be found at http:// from Analytical Chemistry. Innovations in a range of other www.light2015.org. spectroscopic techniques are reported in our contributed Ap- Within the American Chemical Society, Harry A. Atwater, Edi- plications notes. We hope that you enjoy this selection, and as tor in Chief of the journal ACS Photonics, noted in his editorial always welcome your comments. from January 20151, “As proud sponsors of the International Year of Light, in this issue, and during this year, we will join References together with other professional societies around the world to 1. http://pubs.acs.org/doi/pdf/10.1021/acsphotonics.5b00001 celebrate the role of light in science and technology.” 2. http://cen.acs.org/articles/93/i7/Raman-Technique-Helps- In February this year, C&EN Senior Editor Celia Arnaud Surgeons-Excise.html highlighted a brilliant example of researchers using light for the 3. Sci. Transl. Med. 2015, DOI: 10.1126/scitranslmed.aaa2384 direct benefi t of human health2, specifi cally a tool that enables neurosurgeons to differentiate between healthy and cancerous Vicki Mountain, Ph.D. is a contributing editor on this C&EN cells during surgery to remove brain cell tumors.3 As Arnaud Supplement and is a freelance science editor and writer based explains in her story, this is a breakthrough for neurosurgeons in Medford, MA.

3 TOP TEN SPECTROSCOPY, AND MATERIALS ANALYSIS PAPERS Analytical Chemistry’s Most Popular Papers of 2014

OW HAVE the ˇ elds of spectroscopy and materials analysis changed it was last the focus of our special supplement to C&EN in June 2014? With their Hunique perspective on chemical research, the Editors of Analytical Chemistry have answered this question by selecting from their archives, reports that they consider representative of the 10 most signiˇ cant advances in these areas from this last year. To whet your appetites, we have reproduced the abstracts of these noteworthy papers below, along with links to the articles to ˇ ll up on later. Keep current with the latest developments in this ˇ eld throughout 2015 by reading the most recent publications at http://pubs.acs.org/journal/ancham

Universal Surface-Enhanced Raman Scattering ligand for targeting Amplifi cation Detector for Ultrasensitive Detection a receptor. We of Multiple Target Analytes observed that the quenched Jing Zheng, Yaping Hu, Junhui Bai, Cheng Ma, Jishan Li, photolumines- Yinhui Li, Muling Shi, Weihong Tan, and Ronghua Yang cence of the State Key Laboratory of Chemo/Biosensing and Chemometrics, glyco- College of Chemistry and Chemical Engineering, College of Biology, sides functional- and Collaborative Innovation Center for Chemistry and Molecular ized QDs could be Medicine, Hunan University, Changsha, Hunan 410082, China signifi cantly Anal. Chem., 2014, 86 (4), 2205–2212 recovered by a DOI: 10.1021/ac404004m specifi c lectin that selectively binds to the glycosides clustering the QDs but was not affected by a panel of nonspecifi c lectins. Here, we describe a novel “switch-on” biosensor based on Moreover, we determined that quinonyl galactoside functionalized quinonyl glycosides functionalized quantum dots (QDs) for the QDs could optically image the asialoglycoprotein receptors of a specifi c targeting and imaging of transmembrane glycoprotein hepatoma cell line in a target-specifi c manner. This system might receptors on the surface of cancer cells. The design of the provide new insights into the fabrication of photoluminogenic quinonyl glycosides lies in that the quinone moiety serves as a biosensors for the analysis of the universal ligand–receptor quencher of QDs and the glycoside moiety as a biospecifi c recognitions in nature. ◾

Target-Specifi c Imaging of Transmembrane Re- Shanghai, P. R. China ceptors Using Quinonyl Glycosides Functionalized ‡ National Center for Drug Screening, State Key Laboratory of Quantum Dots Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Wei Ma †, Hui-Ting Liu †, Xiao-Peng He †, Yi Zang ‡, Jia Li Shanghai, P. R. China *‡, Guo-Rong Chen †, He Tian †, and Yi-Tao Long † Anal. Chem., 2014, 86 (11), 5502–5507 † Key Laboratory for Advanced Materials & Institute of Fine DOI: 10.1021/ac501463u Chemicals, East China University of Science and Technology,

4 C&EN SUPPLEMENT • MAY 2015 ADVANCES IN SPECTROSCOPY AND MATERIALS ANALYSIS

Here, we describe a novel “switch-on” biosensor based on be signifi cantly recovered by a specifi c lectin that selectively binds quinonyl glycosides functionalized quantum dots (QDs) for the to the glycosides clustering the QDs but was not affected by a specifi c targeting and imaging of transmembrane glycoprotein panel of nonspecifi c lectins. Moreover, we determined that receptors on the surface of cancer cells. The design of the quinonyl galactoside functionalized QDs could optically image the quinonyl glycosides lies in that the quinone moiety serves as a asialoglycoprotein receptors of a hepatoma cell line in a target- quencher of QDs and the glycoside moiety as a biospecifi c ligand specifi c manner. This system might provide new insights into the for targeting a receptor. We observed that the quenched photolu- fabrication of photoluminogenic biosensors for the analysis of the minescence of the quinone glycosides functionalized QDs could universal ligand–receptor recognitions in nature. ◾

Fiber-Enhanced Raman Multigas Spectroscopy: A of magnitude Versatile Tool for Environmental Gas Sensing and and within a Breath Analysis second mea- surement time. Stefan Hanf †, Robert Keiner †, Di Yan †, Jürgen Popp †‡§, The high and Torsten Frosch †‡ potential of FERS † Leibniz Institute of Photonic Technology, Jena, Germany for the detection ‡ Institute for Physical Chemistry, Friedrich-Schiller University, of disease Jena, Germany markers was § Abbe School of Photonics, Friedrich-Schiller University, Jena, demonstrated Germany with the analysis of 27 nL of exhaled human breath. The natural 13 14 15 Anal. Chem., 2014, 86 (11), 5278–5285 isotopes CO2 and N N were quantifi ed at low levels, DOI: 10.1021/ac501463u simultaneously with the major breath components N2, O2, and 12 13 14 15 CO2. The natural abundances of CO2 and N N were Versatile multigas analysis bears high potential for environmental experimentally quantifi ed in very good agreement to theoretical sensing of climate relevant gases and noninvasive early stage values. A fi ber adapter assembly and gas fi lling setup was diagnosis of disease states in human breath. In this contribution, designed for rapid and automated analysis of multigas composi- a fi ber-enhanced Raman spectroscopic (FERS) analysis of a suite tions and their fl uctuations within seconds and without the need of climate relevant atmospheric gases is presented, which for optical readjustment of the sensor arrangement. On the basis allowed for reliable quantifi cation of CH4, CO2, and N2O along- of the abilities of such miniaturized FERS system, we expect high 13 side N2 and O2 with just one single measurement. A highly potential for the diagnosis of clinically administered C-labeled improved analytical sensitivity was achieved, down to a sub-parts CO2 in human breath and also foresee high impact for disease per million limit of detection with a high dynamic range of 6 orders detection via biologically vital nitrogen compounds. ◾

Fabrication of Gold Nanoparticle-Embedded Metal– MIL-101 nanocomposites combined the localized surface Organic Framework for Highly Sensitive Surface- plasmon resonance properties of the gold nanoparticles and the Enhanced Raman Scattering Detection high adsorption capability of metal–organic framework, making them highly sensitive SERS substrates by effectively preconcen- Yuling Hu *, Jia Liao, Dongmei Wang, and Gongke Li trating analytes in close proximity to the electromagnetic fi elds at School of Chemistry and Chemical Engineering, Sun Yat-sen the SERS-active metal surface. We discussed the fabrication, University, Guangzhou, Guangdong 510275, China physical characterization, and SERS activity of our novel sub- Anal. Chem., 2014, 86 (8), 3955–3963 strates by measuring the Raman signals of a variety of model DOI: 10.1021/ac5002355 analytes. The SERS substrate was found to be highly sensitive, robust, and amiable to several different target analytes. A SERS Surface-enhanced Raman scattering (SERS) signals strongly rely detection limit of 41.75 and 0.54 fmol for Rhodamine 6G and ben- on the interactions and distance between analyte molecules and zadine, respectively, was demonstrated. The substrate also metallic nanostructures. In this work, the use of a gold nanopar- showed high stability and reproducibility, as well as molecular ticle (AuNP)-embedded metal–organic framework was introduced sieving effect thanks to the protective shell of the metal–organic for the highly sensitive SERS detection. The AuNPs were in situ framework. Subsequently, the potential practical application of grown and encapsulated within the host matrix of MIL-101 by a the novel SERS substrate was evaluated by quantitative analysis solution impregnation strategy. The as-synthesized AuNPs/ of organic pollutant p-phenylenediamine in environmental water

5 and tumor marker alpha-fetoprotein in human serum. The method in environmental water and 79.3% to 107.3% for alpha-fetoprotein showed good linearity between 1.0 and 100.0 ng/mL for p-phen- in human serum. These results foresee promising application of ylenediamine and 1.0–130.0 ng/mL for alpha-fetoprotein with the the novel metal–organic framework based composites as correlation coeffi cients of 0.9950 and −0.9938, respectively. The sensitive SERS-active substrates in both environmental and recoveries ranged from 80.5% to 114.7% for p-phenylenediamine clinical samples. ◾

Raman Spectroscopy Enables Noninvasive Biochem- spectral analysis as a simple, noninvasive method to biochemi- ical Characterization and Identifi cation of the Stage cally characterize healing wounds in mice and to accurately of Healing of a Wound identify different phases of healing of wounds at different time-points. Raman spectra were collected from “splinted” full Rishabh Jain †, Diego Calderon ‡, Patricia R. Kierski ‡, Michael thickness dermal wounds in mice at 4 time-points (0, 1, 5, and 7 J. Schurr §, Charles J. Czuprynski ƒ, Christopher J. Murphy ⊥¶, days) corresponding to different phases of wound healing, as Jonathan F. McAnulty ‡, and Nicholas L. Abbott † † Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States ‡ Department of Surgical Sciences, School of Veterinary Medi- cine, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States § Department of Surgery, School of Medicine and Public Health, University of Colorado-Denver, Denver, Colorado 80217 United States ƒ Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wiscon- sin 53706, United States verifi ed by histopathology. Spectra were deconvolved using ⊥ Department of Surgical and Radiological Sciences, School multivariate factor analysis (MFA) into 3 “factor score spectra” of Veterinary Medicine, University of California-Davis, Davis, (that act as spectral signatures for different stages of healing) that California 95616, United States were successfully correlated with spectra of prominent pure ¶ Department of Ophthalmology & Vision Science, School of wound bed constituents (i.e., collagen, lipids, fi brin, fi bronectin, Medicine, University of California-Davis, Davis, California 95616, etc.) using non-negative least squares (NNLS) fi tting. We show United States that the factor loadings (weights) of spectra that belonged to Anal. Chem., 2014, 86 (8), 3764–3772 wounds at different time-points provide a quantitative measure of DOI: 10.1021/ac500513t wound healing progress in terms of key parameters such as infl ammation and granulation. Wounds at similar stages of Accurate and rapid assessment of the healing status of a wound healing were characterized by clusters of loading values and in a simple and noninvasive manner would enable clinicians to slowly healing wounds among them were successfully identifi ed diagnose wounds in real time and promptly adjust treatments to as “outliers”. Overall, our results demonstrate that Raman hasten the resolution of nonhealing wounds. Histologic and spectroscopy can be used as a noninvasive technique to provide biochemical characterization of biopsied wound tissue, which is insight into the status of normally healing and slow-to-heal currently the only reliable method for wound assessment, is wounds and that it may fi nd use as a complementary tool for invasive, complex to interpret, and slow. Here we demonstrate the real-time, in situ biochemical characterization in wound healing use of Raman microspectroscopy coupled with multivariate studies and clinical diagnosis. ◾

Toward Biocompatible Nuclear Hyperpolarization A. R. Highton ∥, Gary G. R. Green ∥, Alexandra Olaru ∥, Using Signal Amplifi cation by Reversible Exchange: Jürgen Hennig ‡, and Dominik von Elverfeldt ‡ Quantitative in Situ Spectroscopy and High-Field † German Consortium for Cancer Research (DKTK), Heidelberg, Imaging Germany ‡ Medical Physics, Department of Radiology, University Medical Jan-Bernd Hövener †‡§, Niels Schwaderlapp ‡, Robert Center Freiburg, 79098 Freiburg, Germany Borowiak †‡§, Thomas Lickert ‡, Simon B. Duckett ∥, Ryan § German Cancer Research Center (DKFZ), Heidelberg, Ger- E. Mewis ∥, Ralph W. Adams ∥, Michael J. Burns ∥, Louise many

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∥ Centre for Hyperpolarisation in Magnetic Resonance, Univer- manipulations, and which allows in situ detection of thermally sity of York, York, YO10 5DD, U.K. polarized and hyperpolarized samples. We introduce a method Anal. Chem., 2014, 86 (3), 1767–1774 for absolute quantifi cation of hyperpolarization yield in situ by DOI: 10.1021/ac403653q means of a thermally polarized reference. A maximum signal-to- noise ratio of ∼103 for 148 µmol of substance, a signal enhance- Signal amplifi cation by reversible exchange (SABRE) of a ment of 106 with respect to polarization transfer fi eld of SABRE, substrate and parahydrogen at a catalytic center promises to or an absolute 1H-polarization level of ˇ10–2 is achieved. In an overcome the inherent insensitivity of magnetic resonance. In important step toward biomedical application, we demonstrate order to apply the new approach to biomedical applications, 1H in situ NMR as well as 1H and 13C high-fi eld MRI using 13 there is a need to develop experimental equipment, in situ hyperpolarized pyridine (d3) and C nicotinamide in pure and quantifi cation methods, and a biocompatible solvent. We 11% ethanol in aqueous solution. Further increase of hyperpo- present results detailing a low-fi eld SABRE polarizer which larization yield, implications of in situ detection, and in vivo provides well-controlled experimental conditions, defi ned spins application are discussed. ◾

Structural and Optical Nanoengineering of Nanopo- tic peak position produced by small changes in the effective rous Anodic Alumina Rugate Filters for Real-Time medium (i.e., refractive index). To this end, NAA-RFs are fi lled and Label-Free Biosensing Applications with different solutions of D-glucose, and the Δλpeak is mea- sured in real time by RfS. These results are validated by a Tushar Kumeria †, Mohammad Mahbubur Rahman †‡, theoretical model (i.e., the Looyenga–Landau–Lifshitz model), Abel Santos †, Josep Ferré-Borrull ‡, Lluís F. Marsal ‡, demonstrating that the control over the nanoporous structure and Dusan Losic † makes it possible to optimize optical signals in RfS for sensing † School of Chemical Engineering, The University of Adelaide, purposes. The Engineering North Building, 5005 Adelaide, Australia linear range of ‡ Departament d’Enginyeria Electrònica, Elèctrica i Automàtica, these optical Universitat Rovira i Virgili, Avda Països Catalans 26, 43007 Tar- sensors ragona, Spain ranges from Anal. Chem., 2014, 86 (3), 1837–1844 0.01 to 1.00 M, DOI: 10.1021/ac500069f with a low In this study, we report about the structural engineering and detection limit optical optimization of nanoporous anodic alumina rugate fi lters of 0.01 M of (NAA-RFs) for real-time and label-free biosensing applications. D-glucose (i.e., Structurally engineered NAA-RFs are combined with refl ection 1.80 ppm), a sensitivity of 4.93 nm M–1 (i.e., 164 nm per spectroscopy (RfS) in order to develop a biosensing system refractive index units), and a linearity of 0.998. This proof-of- based on the position shift of the characteristic peak in the concept study demonstrates that the proposed system combin- refl ection spectrum of NAA-RFs (Δλpeak). This system is ing NAA-RFs with RfS has outstanding capabilities to develop optimized and assessed by measuring shifts in the characteris- ultrasensitive, portable, and cost-competitive optical sensors. ◾

In Vivo Proton–Electron Double-Resonance Imag- 43210, United States ing of Extracellular Tumor pH Using an Advanced ∥ Vorozhtsov Institute of Organic Chemistry, Novosibirsk Nitroxide Probe 630090, Russia ⊗ Hokkaido University, Sapporo, Hokkaido 060-0814, Japan Alexandre Samouilov †§, Olga V. Efi mova †, Andrey A. Anal. Chem., 2014, 86 (2), 1045–1052 Bobko †‡, Ziqi Sun †, Sergey Petryakov †, Timothy D. DOI: 10.1021/ac402230h Eubank †‡, Dmitrii G. Trofi mov ∥, Igor A. Kirilyuk ∥, Igor A. Grigor’ev ∥, Wataru Takahashi †⊗, Jay L. Zweier †§, and A variable radio frequency proton–electron double-resonance Valery V. Khramtsov †‡ imaging (VRF PEDRI) approach for pH mapping of aqueous †The Dorothy M. Davis Heart and Lung Research Institute: samples has been recently developed (Efi mova et al. J. Magn. ‡Division of Pulmonary, Allergy, Critical Care, and Sleep Medi- Reson. 2011, 209, 227−232). A pH map is extracted from two cine, and §Division of Cardiovascular Medicine, Department of PEDRI acquisitions performed at electron paramagnetic Internal Medicine, The Ohio State University, Columbus, Ohio resonance (EPR) frequencies of protonated and unprotonated

7 forms of a pH-sensitive probe. To translate VRF PEDRI to an in ogy. The probe demonstrated pH sensitivity in the 5.8–7.8 vivo setting, an advanced pH probe was synthesized. Probe range, optimum for measurement of acidic extracellular tumor deuteration resulted in a narrow spectral line of 1.2 G com- pH (pHe). In vivo VRF PEDRI was performed on Met-1 tumor- pared to a nondeuterated analogue line width of 2.1 G bearing mice. Compared to normal mammary glands with a allowing for an increase of Overhauser enhancements and neutral mean pHe (7.1 ± 0.1), we observed broader pH reduction in rf power deposition. Binding of the probe to the distribution with acidic mean pHe (6.8 ± 0.1) in tumor tissue. cell-impermeable tripeptide, glutathione (GSH), allows for In summary, VRF PEDRI in combination with a newly devel- targeting to extracellular tissue space for monitoring extracel- oped pH probe provides an analytical approach for spatially lular tumor acidosis, a prognostic factor in tumor pathophysiol- resolved noninvasive pHe monitoring, in vivo. ◾

Direct Detection and Speciation of Trace to a nondeu- Using a Nanoporous Multifunctional Microcantilever terated analogue line Dongkyu Lee †, Seonghwan Kim †‡, Sangmin Jeon §, and width of 2.1 G Thomas Thundat † allowing for an † Department of Chemical and Materials Engineering, University increase of of Alberta, Edmonton, Alberta T6G 2 V4, Canada Overhauser ‡ Department of Mechanical and Manufacturing Engineering, enhancements University of Calgary, Calgary, Alberta T2N 1N4, Canada and reduction § Department of Chemical Engineering, Pohang University of in rf power Science and Technology, Pohang, South Korea deposition. ∥ Vorozhtsov Institute of Organic Chemistry, Novosibirsk Binding of the 630090, Russia probe to the ⊗ Hokkaido University, Sapporo, Hokkaido 060-0814, Japan cell-imperme- Anal. Chem., 2014, 86 (10), 5077–5082 able tripeptide, glutathione (GSH), allows for targeting to DOI: 10.1021/ac500745g extracellular tissue space for monitoring extracellular tumor acidosis, a prognostic factor in tumor pathophysiology. The A variable radio frequency proton–electron double-resonance probe demonstrated pH sensitivity in the 5.8–7.8 range, imaging (VRF PEDRI) approach for pH mapping of aqueous optimum for measurement of acidic extracellular tumor pH samples has been recently developed (Efi mova et al. J. Magn. (pHe). In vivo VRF PEDRI was performed on Met-1 tumor-bear- Reson. 2011, 209, 227−232). A pH map is extracted from two ing mice. Compared to normal mammary glands with a neutral

PEDRI acquisitions performed at electron paramagnetic mean pHe (7.1 ± 0.1), we observed broader pH distribution with resonance (EPR) frequencies of protonated and unprotonated acidic mean pHe (6.8 ± 0.1) in tumor tissue. In summary, VRF forms of a pH-sensitive probe. To translate VRF PEDRI to an in PEDRI in combination with a newly developed pH probe vivo setting, an advanced pH probe was synthesized. Probe provides an analytical approach for spatially resolved noninva- deuteration resulted in a narrow spectral line of 1.2 G compared sive pHe monitoring, in vivo.

Detection and Quantifi cation of Early-Stage Malaria DOI: 10.1021/ac500199x Parasites in Laboratory Infected Erythrocytes by Attenuated Total Refl ectance Infrared Spectroscopy New diagnostic modalities for malaria must have high sensitiv- and Multivariate Analysis ity and be affordable to the developing world. We report on a method to rapidly detect and quantify different stages of malaria Aazam Khoshmanesh †, Matthew W. A. Dixon ‡, Shannon parasites, including ring and gametocyte forms, using attenuated Kenny ‡, Leann Tilley ‡, Don McNaughton †, and Bayden total refl ectance Fourier transform infrared spectroscopy (ATR- R. Wood † FT-IR) and partial least-squares regression (PLS). The absolute † Centre for Biospectroscopy and School of Chemistry, Monash detection limit was found to be 0.00001% parasitemia (<1 para- University, Clayton, Victoria 3800, Australia site/µL of blood; p < 0.008) for cultured early ring stage parasites ‡ Department of Biochemistry and Molecular Biology and Bio21 in a suspension of normal erythrocytes. Future development of Molecular, Science and Biotechnology Institute, The University universal and robust calibration models can signifi cantly improve of Melbourne, Melbourne, Victoria 3010 Australia malaria diagnoses, leading to earlier detection and treatment of Anal. Chem., 2014, 86 (9), 4379–4386 this devastating disease.

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DETECTION OF METHYLMALONIC ACID (MMA) IN PLASMA USING HYDROPHILIC INTERACTION LIQUID CHROMATOGRAPHY (HILIC) COUPLED WITH MASS SPECTROMETRY (MS) OR TANDEM MASS SPECTROMETRY (MS/MS) Maricar Dube and Patrik Appelblad EMD Millipore

Abstract Experimental Conditions Methylmalonic acid (MMA) is a biomarker for vitamin B12 defi ciency. This application note describes a fast, simple, and Chromatography Conditions sensitive method to detect MMA in plasma that uses a zwit- terionic hydrophilic interaction chromatography (ZIC®-HILIC) Table 1 column with LC-MS or LC-MS/MS. Column SeQuant® ZIC®-HILIC (3µm, 100Å) PEEK 100× 2.1 mm Introduction Injection 7 µL Methylmalonic acid (MMA) levels in serum, plasma and urine Mobile phase 80:20 Acetonitrile/ 100 mM ammonium ac- are used to monitor cobalamin (vitamin B12) defi ciency1 and etate pH 4.5* methylmalonic acidemia. Different methods have been devel- Flow rate 400 µL/min oped to quantify MMA in biological samples, including GC-MS, Temperature 40oC LC-MS/MS, HPLC, and capillary electrophoresis (CE). The main (a) ESI-MS challenges that must be overcome for accurate measurement Detection (b) MS/MS, ESI(-), are the low physiological concentrations of MMA in human MRM (m/z 117.1→73.0, 55.1) serum (100-500 nM), and the fact that MMA is a hydrophilic * There is a gradient wash process between injections non-volatile compound. Retention and separation of MMA on reversed phase liquid chromatographic columns is diffi cult since MMA is poorly retained, and the structural isomer, suc- Sample Preparation cinic acid (SA), causes ion suppression because the concentra- 800 µL acidifi ed acetonitrile containing 170 nM of internal tion SA in serum is usually considerably higher than MMA. standard (D3-MMA) was used to precipitate proteins in 200 µL Many laboratories have adopted protocols that require serum/plasma samples. Supernatant was directly injected into extraction of MMA plus steps to yield MMA-derivatives that the column after centrifugation3. are compatible with GC-MS or LC-MS/MS techniques using reversed phase columns2. This way, derivatives of MMA and Results and Discussion SA may be differentiated due to their different fragmentation Isocratic separation of MMA in plasma on a ZIC®-HILIC col- patterns. As a consequence however, the cost per MMA-test umn was achieved in less than 3 minutes. The void volume was is usually considerably higher than standard immunological 0.5 min, while the retention times for MMA and D3-MMA were assays for B12. 2.14 min and 2.13 min, respectively. HILIC columns effi ciently separate polar hydrophilic com- For the single stage MS detection, the limit of detection (3 x pounds, which are not retained on reversed phase columns. SD) and limit of quantitation (10 x SD) were 30 nM and 90 nM The base material of HILIC columns can be either silica or MMA, respectively, in plasma/serum. The method is linear up to polymer, and may be modifi ed with different types of polar func- 200 µM. Day-to-day and intra-day CVs are lower than 5%. The tionalities such as zwitterionic sulfoalkylbetaine (ZIC®-HILIC recovery is between 90% and 93%. column). Because of its highly polar nature, MMA is retained For the MS/MS detection, the limit of detection (3 × SD) was on a ZIC®-HILIC column without the need to generate MMA- 5 nM and the limit of quantifi cation (10 × SD) for MMA was 15 derivatives, making the workfl ow simpler, easier and faster3. nM. Figure 1 (on next page) shows the MS/MS chromatogram This report describes a sensitive LC-MS/MS method to measure of MMA in a plasma sample. MMA using a ZIC®-HILIC column.

9 Figure 1. ZIC®-HILIC-MS/MS chromatogram of MMA (m/z 117.1 73.0) and D3-MMA (m/z 119.9 75.9) in a plasma sample

Conclusion methylmalonic acid and total homocysteine concentrations. A fast, simple, and sensitive means to determine MMA 1990 . Am. J. Hemato. Jun. 34(2): 90–98 levels in serum/plasma was developed that combined ZIC®- 2. Schneede, J. and Ueland, P.M. Automated assay of methyl- HILIC separation with single stage negative ESI-MS or tandem malonic acid in serum and urine by derivatization with 1-py- MS. As neither MMA sample extraction nor derivatization were renyldiazomethane, liquid chromatography, and fl uores- required, the ZIC®-HILIC-MS/MS method reported here may be cence detection. 1993. Clin. Chem. Mar. 39(3): 392–399 an attractive alternative to existing means for measuring MMA 3. Lakso, H.-A., Appelblad, A., and Schneede, J. in clinical laboratories where the existing GC-MS or reversed Quantifi cation of methylmalonic acid in human plasma with phase LC-MS/MS methods are tedious and laborious. hydrophilic interaction liquid chromatography separation and mass spectrometric detection. 2008 . Clin. Chem. Dec. 54(12): References 2028-2035 1. Allen, R.H., Stabler, S.P., Savage, D.G., and Lindenbaum, J. Diagnosis of cobalamin defi ciency I: usefulness of serum

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DUAL-FLOW REFRACTIVE INDEX DETECTOR FOR DETERMINATION OF MOLAR MASS AVERAGES IN GEL PERMEATION CHROMATOGRAPHY Amandaa K. Brewer, Ph.D. Tosoh Bioscience LLC

Introduction GPC System for the determination of molar mass averages via Gel permeation chromatography (GPC) is the most widely ac- peak position calibration. The unique dual fl ow design of the RI cepted and used analytical method for obtaining molar mass detector is constructed in such a way that the reference side of averages and distributions of both synthetic and biological the RI fl ow cell contains a fl owing stream of pure solvent. The polymers. Traditionally, molar mass averages and distributions dual fl ow design is shown to compensate for the changes in the are obtained via a peak position calibration using a series of refractive index of the solvent over time by continuously fl owing standards of known molar mass and chemistry, analyzed by pure solvent through the reference side of the fl ow cell. GPC coupled to a differential refractive index (RI) detector. In the context of GPC, GPC/RI continues to be heavily employed Experimental Methods and Conditions as it provides excellent day-to-day reproducibility, and is ideal GPC analysis was performed on a system consisting of either for quality control procedures. an all-in-one EcoSEC GPC System equipped with a dual-fl ow One caveat to single detector GPC performance is the refractive index detector or a modular HPLC system with an baseline stability of the RI detector. A conventional RI detector external conventional refractive index detector. Separation is constructed in such a way that there are two sides: (1) the of polystyrene standards (PS) occurred over a column blank reference side that contains stagnant pure solvent; and (2) the consisting of TSKgel® SuperMultiporeHZ-M columns, with THF sample side, which has a fl owing stream of analyte in the same as the mobile phase. solvent as in the reference side. Over time, the stagnant pure solvent in the reference side slowly changes, resulting in base- Results and Discussion line drift. For peak position calibration, a drift in the RI baseline To demonstrate the repeatability, reproducibility, and baseline has been shown to drastically affect the accuracy and precision stability of a dual-fl ow RI detector compared to a conventional of measurements of molar mass averages and distributions RI detector a series of identical experiments was performed with an increase in the error rate of 25%. on the EcoSEC GPC System (Figure 1) and two conventional Here, we have studied the repeatability, reproducibility, and baseline stability of a dual-fl ow RI detector in the EcoSEC®

Figure 1 Figure 2 EcoSEC GPC System Baseline drift comparison between a dual-fl ow refractive index detector and conventional systems

11 HPLC systems. As shown in Figure 2, fi ve consecutive injec- the conventional RI detector produced day-to-day variations in tions of PS with run times of one hour without auto zeroing the molar mass averages between 1% and 3%. detector between injections for a total of fi ve hours, resulted in an extremely stable baseline with low baseline drift for the dual- Conclusion fl ow RI detector and a signifi cantly drifting baseline on the two A stable RI detector baseline is required for successful experi- conventional RI detectors. ments, and repeatable and reproducible molar mass averages. The repeatability and reproducibility of the molar mass Extreme care must be taken when molar mass averages and averages as obtained via the dual-fl ow and conventional RI de- distributions are determined via peak position calibration as tectors were also compared. The reproducibility of the weight- uncertainties and instabilities in the RI baseline can result in rela- average molar mass, Mw, of the dual-fl ow RI detector was tively large errors, inconsistencies, and deviations in molar mass determined to be superior by a factor of 3 to that of a conven- averages. The repeatability and reproducibility of the molar tional RI detector. Additionally the day-to-day reproducibility and mass averages were shown to increase greatly when a conven- repeatability for the determination of molar mass averages was tional RI detector was replaced with a dual-fl ow RI detector. shown to vary less than 0.5% for the dual-fl ow RI detector, while

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MODULAR SPECTROSCOPY TOOLS FOR MEASURING INTRINSIC PROTEIN FLUORESCENCE Yvette Mattley, Ph.D. Ocean Optics

Abstract chemical agents such as guanidine hydrochloride or urea, and In this application note, a UV LED and a high performance mod- changing pH. As the protein unfolds, amino acids previously ular spectrometer were used together to measure the intrinsic buried in the hydrophobic core of the protein are exposed to fl uorescence of the protein lysozyme in different conformational the solvent. Solvent exposure quenches the fl uorescence of the states. The objective was to demonstrate the power of modular amino acids and decreases the intensity of the intrinsic protein spectroscopy for measuring inherent protein fl uorescence as a spectrum. means to monitor changes in the folded state of proteins. Experimental Conditions Introduction A 280 nm UV LED in combination with a high-sensitivity QE Pro Proteins contain aromatic amino acids that fl uoresce when spectrometer was used to measure fl uorescence from samples excited with UV light. This intrinsic protein fl uorescence de- of lysozyme diluted in neutral and acidic solutions. We prepared pends on the amino acid composition and conformational state 3 mg/mL lysozyme (L6876 Sigma) in phosphate buffered saline of the protein. As the protein goes from a native (folded) to a (1X PBS pH 7.4), and 0.1 M HCl/KCl (pH 1) solution. Lysozyme denatured (unfolded) state, the local environment surrounding suspended in 1X PBS was in its native (folded) state, while lyso- the aromatic amino acids changes, affecting the fl uorescence zyme suspended in the acidic 0.1 M HCl/KCl solution began to properties of the amino acids. denature and expose amino acids previously contained within Proteins containing tryptophan and tyrosine (280 nm and the core of the protein to the solvent environment. 274 nm excitation, respectively) are best suited for conformation monitoring by UV-excited fl uorescence emissions due to the Results and Discussion relatively high quantum yield and similar excitation wavelengths The intrinsic protein fl uorescence spectra for lysozyme diluted in of these amino acids. Phenylalanine is used less frequently 1X PBS (neutral pH) and 0.1 M HCl/KCl (acidic pH) are shown as an indicator of protein conformation because it has a in Figure 1. When lysozyme was exposed to low pH, the protein much lower quantum yield with a lower excitation wavelength conformation changed exposing the tryptophan and tyrosine (~257 nm excitation). amino acids to a different environment. As a result, the fl uores- The native state of a protein can be altered in different ways cence spectrum decreased in intensity as the protein changed including elevating temperature, adding chaotropic or other from a folded conformation to an unfolded state.

Conclusion Intrinsic fl uorescence is a powerful indicator of protein structure and function. Inherent protein fl uorescence can give research- ers insight into the protein’s conformational state, and corre- sponding biological activity under different conditions, including changes in temperature, pH and ion concentration. These changes in intrinsic protein fl uorescence can be used to moni- tor protein unfolding for medical diagnostics applications where researchers are investigating neurodegenerative and other diseases associated with improper protein unfolding.

Ocean Optics, Inc. 830 Douglas Avenue, Dunedin, FL 34698 Tel: (727) 733-2447 Figure 1 Email: [email protected] Changes in the fl uorescence spectra of lysozyme with exposure to a low-pH Website: www.oceanoptics.com

13 ON-LINE QUALITY CONTROL MEASUREMENTS IN VARYING CONDITIONS Yvette Mattley, Ph.D. Ocean Optics

Abstract Experimental Conditions With the use of a new generation of robust, repeatable and To evaluate the effectiveness of the Flame spectrometer at stable instrumentation, manufacturers can more easily assess different temperatures, we measured transmission of several sample quality under rigorous conditions. In this application note, we investigate the thermal stability of a spectrometer system for process line transmission measurements at different temperatures.

Introduction Even as advances in engineering technologies and manufactur- ing processes have lowered the cost of making and distributing products, the demand for continued improvement is as strong as ever. In an environment where small improvements in character- ization of raw materials or subtle changes in process parameters can result in signifi cant production savings, the ability to design faster, smarter and more robust instrumentation is paramount. When the emergence of miniature spectrometers coincided with development of modular fi ber optics, spectroscopy was no longer limited to the lab. Now you can bring the instrument to the sample, which allows industrial users to integrate the measure- ment into the process. Small-footprint modular systems can be rapidly confi gured for a variety of absorbance, refl ectance and Figure 2 Mixture 1: spectra measured across each temperature condition – chilled (24 °C), emission measurements, with a number of potential applications. ambient (27 °C) and heated (30 °C) – were consistent. The Flame spectrometer addresses some of the limitations associated with miniature spectroscopy systems in dynamic process environments.

Figure 1 Figure 3 Water was tested as the reference for each condition – chilled (24 °C), ambient (27 The Flame spectrometer produced consistent results across different temperature °C) and heated (30 °C). conditions, as these transmission spectra reveal.

14 C&EN SUPPLEMENT • MAY 2015 ADVANCES IN SPECTROSCOPY AND MATERIALS ANALYSIS

concentration levels of food dye mixtures on a simulated within the stream. For quality control professionals, getting the process line with typical conditions encountered in a process correct answers under all sorts of conditions—including tem- environment. Then we isolated each Flame spectrometer in perature extremes—is critical. a different temperature environment – cool (using a chiller), ambient and hot (using a lab heater). Several sample mixtures Conclusion were prepared for testing, using the Z-type fl ow cell to move Process environments can be harsh, with extremes in tem- each sample through the system. Water moving through the perature and humidity, and the harmful effects of dust and fl ow cell was measured as a reference (Figure 1). vibration. That’s why process-ready spectroscopic instrumen- tation such as Flame has been designed with few moving Results and Discussion parts, has a high degree of thermal stability, and is easily Although the Flame spectrometers measured the transmission adapted for different setups. The availability of such robust, of the mixtures fl owing through the system at different tempera- repeatable, thermally stable instrumentation allows manu- ture conditions, the resulting spectra—and sample composition facturers to assess sample quality online at multiple points information derived from the spectra—were nearly identical in processes, helping to improve yields, eliminate waste and (Figure 2 and Figure 3). This result is signifi cant for process line reduce costs. applications, where temperatures can vary from zone to zone

Ocean Optics, Inc. 830 Douglas Avenue, Dunedin, FL 34698 Tel: (727) 733-2447 Email: [email protected] Website: www.oceanoptics.com

Now accepting submissions Research at the intersection of chemistry, biology, materials science, and engineering>>>

ACS Publications is pleased to introduce > New biomaterials, bioinspired and ACS Biomaterials Science & Engineering, biomimetic approaches to biomaterials a new journal formed to address the rapid > Biomaterial interfaces, health risk pubs.acs.org/biomaterials growth, fueled by the biomedical and studies of biomaterials biotechnology industries. > Bioelectronics, bioMEMS, biomaterials Manuscripts will cover a broad spectrum of based devices and prosthetics topics including: > Regenerative medicine, biomaterial EDITOR-IN-CHIEF > Modeling and informatics tools technology for tissues, genetic designs David L. Kaplan for biomaterials and bioengineering Tufts University

15 THERMOPLASTIC ELASTOMER FLOW PROPERTY DETERMINATION BY DYNAMIC RHEOLOGY TA Instruments

Abstract ber and elastomer characterization. Pre-molded sample discs Rate-dependent viscosity data of thermoplastic elastomers is were used to improve homogeneity. Samples were loaded at important for effective material property prediction and manu- 180°C and conditioned with a low strain and frequency (0.5%, facturing process design. Rheological data also reveals compo- 10 rad/s) for 10 minutes prior to data collection. Frequency sitional differences and the presence of a percolation threshold sweep experiments were performed at 1% strain. of the dispersed phase. Results Introduction Four samples were tested, each with a different TPV content, to Thermoplastic elastomers have gained considerable interest for demonstrate shear-thinning behavior, which is common for poly- their appealing combination of rubber-like fi nal properties and mers. At moderate to high frequencies (shear rates), the complex convenient thermoplastic processing. Thermoplastic vulcani- viscosity values are similar for each specimen (Figure 1a). Larger zates (TPV) are among the most prevalent thermoplastic elas- differences become evident at low frequencies, which correlate tomers for the replacement of cured rubber parts. TPV can be with low shear rate behavior. The fourth sample (Figure 1, black processed like thermoplastics, however characterization of their curve) exhibits a Newtonian viscosity plateau at low frequencies. fl ow behavior is critical to effective manufacturing design. Many TPV producers offer material grades based on both variable Discussion hardness and tailor-made processing types such as injection TPV are multiphase materials with a discontinuous cured rubber molding, blow molding or extrusion. phase dispersed in a continuous polyolefi n phase. The ratio of

a. cured rubber to polyolefi n is used to adjust the fi nal hardness val- ue; greater polyolefi n content leads to higher hardness values. In Figure 1, the specimen indicated by the black curve has a hard- ness value of 50 Shore D, indicative of a polyolefi n-rich material. All other materials (red, blue, and green curves) have hardness values from 50 to 75 Shore A, and are rubber-rich materials. The viscous behavior of the low-hardness materials (high rubber-phase content) can be appropriately described by the n Herschel-Bulkley model: σ = σc+K (γ ̇) This model is specifi cally used for compounded materials such as rubbers and plastics with fi ller content above the per- colation threshold. This model highlights a critical stress ( c) at which the viscosity is infi nite and under which the material does not fl ow, information that is particularly important for injection mold and extruder die design. The critical stress for rubber-rich TPV is clearly illustrated in Figure 1b. This representation of the data also reinforces the earlier conclusion that the polyolefi n- rich material (black curve) does not exhibit a critical stress.

Figure 1 (a) Frequency dependent complex viscosity of four TPV materials of varying com- position. (b) Rubber content of samples and corresponding yield stress

Experimental Conditions Samples of TPV of varying composition were tested with the TA Instruments 159 Lukens Drive RPA elite oscillatory shear rheometer (TA Instruments, New New Castle, DE 19720 Castle, DE USA). The RPA elite is a closed-cavity dynamic Email: [email protected] shear rheometer with grooved biconical dies designed for rub- Website: www.tainstruments.com

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