APRIL 18, 2016

Getting the good stuff out of chicken manureP.21

Data falsification clouds India’s drug sectorP.23

This wristband tracks the chemicals you encounter

every dayP.30

Serving All Your Life Cycle Needs

Pharma&Biotech

www.lonza.com

Lonza’s Peptide Experts Provide Total Life Cycle Management

from Feasibility Studies through Commercial Supply

Lonza recognizes the importance of starting with the right materials and

maintaining stability of supply through every phase of the product life

cycle. Partner with us for reliable custom peptides at every stage, and

every scale.

– Early Intermediate (GMP, non-GMP)

– Development technology services for solid and liquid

phase synthesis

– Advanced Peptide Intermediates

– Bulk Actives/Drug Substance

– Generic Peptidespeptides@lonza.com

North America +1 201 316 9200 Europe +41 61 316 8111

C E N E A R 9 4 ( 1 6 ) 1 – 4 0 • I S S N 0 0 0 9 - 23 47

VOLUME 94, NUMBER 16

April 18, 2016

Contents

▲

Photograph by Will Ludwig/C&EN

Tracking everyday chemical

exposuresSilicone wristbands reveal personal exposures to toxic

compounds.Page 30

3 Reactions2 Editor’s Page

5 Concentrates

38 C&ENjobs40 Newscripts

18 Future spending stalls this yearSpin-offs and consolidation take a toll on big chemical fi rms’ outlays for research and construction.

28 C&EN profi les Plant-e, a start-up looking to soil for powerDutch university spin-off seeks to capture electrons from microbes living alongside plant roots.

21 Much ado about chicken pooEnvironmental engineers look for sustainable ways to deal with manure in Maryland.

23 Indian drug fi rms struggle with quality issuesMore and more companies are challenged by U.S. FDA’s scrutiny of manufacturing records.

26 Teaching hazard assessmentEducators move beyond lab safety rules to teach students new skills.

35 ACS Comment36 Awards37 Obituaries

“If we can identify hundreds or thousands of chemicals in a wristband that we didn’t know people were being exposed to, that is a treasure trove.”

—John Wambaugh, physical scientist, EPA’s Office

of Research & Development Page 30

On the cover

Cover story

Departments

Features

ACS News

Quote of the week

2 C&EN | CEN.ACS.ORG | APRIL 18, 2016

From the Editor

Editor-in-chief@BibianaCampos

1155—16th St., N.W., Washington, DC 20036 (202) 872-4600 or (800) 227-5558

EDITOR-IN-CHIEF: Bibiana Campos Seijo MANAGING EDITOR, EDITORIAL: Amanda Yarnell

MANAGING EDITOR, PRODUCTION: Rachel Sheremeta Pepling BUSINESS DEVELOPMENT & PUBLISHER: Kevin A. Davies

SENIOR ADMINISTRATIVE OFFICER: Marvel A. Wills

BUSINESS NEW YORK CITY: (212) 608-6306 Michael McCoy, Assistant

Managing Editor, Rick Mullin (Senior Editor), Marc S. Reisch (Senior Correspondent), Alexander H. Tullo (Senior Correspondent), Rachel Eskenazi (Administrative Assistant). CHICAGO: (917) 710-0924 Lisa M. Jarvis (Senior Correspondent). HONG KONG: 852 9093

8445 Jean-François Tremblay (Senior Correspondent). HOUSTON: (281) 486-3900 Ann M. Thayer (Senior Correspondent). LONDON:

44 1494 564 316 Alex Scott (Senior Editor). WEST COAST: (315) 825-8566 Melody M. Bomgardner (Senior Editor)

GOVERNMENT & POLICY Cheryl Hogue, Assistant Managing Editor

Britt E. Erickson (Senior Editor), Jessica Morrison (Associate Editor), Andrea L. Widener (Senior Editor)

SCIENCE/TECHNOLOGY/EDUCATION WASHINGTON: Lauren K. Wolf, Assistant Managing Editor

Celia Henry Arnaud (Senior Editor), Stuart A. Borman (Senior Correspondent), Matt Davenport (Associate Editor), Stephen K. Ritter (Senior Correspondent). BERLIN: 49 30 2123 3740 Sarah Everts (Senior Editor). BOSTON: (973)

922-0175 Bethany Halford (Senior Editor). CHICAGO: (847) 679-1156 Mitch Jacoby (Senior Correspondent). WEST COAST: (626) 765-6767

Michael Torrice (Deputy Assistant Managing Editor), (925) 226-8202 Jyllian Kemsley (Senior Editor), (510) 390-6180 Elizabeth K. Wilson (Senior Editor)

JOURNAL NEWS & COMMUNITY: (510) 768-7657 Corinna Wu (Senior Editor)

(651) 447-6226 Jessica H. Marshall (Associate Editor)

ACS NEWS & SPECIAL FEATURES Linda Wang (Senior Editor)

EDITING & PRODUCTION Kimberly R. Bryson, Assistant Managing Editor

Craig Bettenhausen (Associate Editor), Mitch A. Garcia (Assistant Editor), Jeff A. Huber (Associate Editor), Manny I. Fox Morone (Associate Editor),

Alexandra A. Taylor (Contributing Editor)

CREATIVE Robert Bryson, Creative Director

Tchad K. Blair, Interactive Creative DirectorRobin L. Braverman (Senior Art Director), Ty A. Finocchiaro

(Senior Web Associate), Yang H. Ku (Art Director),William A. Ludwig (Associate Designer)

DIGITAL PRODUCTION Renee L. Zerby, Manager, Digital Production

Luis A. Carrillo (Web Production Manager), Marielyn Cobero (Digital Production Associate), Joe Davis (Lead Digital Production Associate),

Krystal King (Lead Digital Production Associate), Shelly E. Savage (Senior Digital Production Associate), Cesar Sosa (Digital Production Associate)

PRODUCTS MANAGER: Pamela Rigden Snead

SALES & MARKETING Stephanie Holland, Manager, Advertising Sales & Marketing

Natalia Bokhari (Digital Advertising Operations Manager), Kirsten Dobson (Advertising and Marketing Associate), Sondra Hadden (Senior Digital

Marketing Specialist)

ADVISORY BOARD Deborah Blum, Raychelle Burks, Kendrew H. Colton, François-Xavier Coudert,

Cathleen Crudden, Paula T. Hammond, Matthew Hartings, Christopher Hill,Peter Nagler, Dan Shine, Michael Sofia, Michael Tarselli, William Tolman,

James C. Tung, Jill Venton, Helma Wennemers, Geofrey K. Wyatt

Published by the AMERICAN CHEMICAL SOCIETY Thomas M. Connelly Jr., Executive Director & CEOBrian D. Crawford, President, Publications Division

EDITORIAL BOARD: Nicole S. Sampson (Chair),ACS Board of Directors Chair: Pat N. Confalone,

ACS President: Donna J. Nelson, Cynthia J. Burrows, Michael P. Doyle, Jerzy Klosin, Gary B. Schuster

Copyright 2016, American Chemical SocietyCanadian GST Reg. No. R127571347

Volume 94, Number 16

This spring we commemorate a couple of quite important an-niversaries: The first one is the fifth anniversary of Fukushima’s

nuclear disaster; the second one is the 30th anniversary of the explosion of the main re-actor at Chernobyl’s nuclear power plant.

Both events happened within my lifetime, and I remember those days quite vividly. In particular, I recall my whole family sitting to-gether staring at the television watching he-licopters fly over Chernobyl dropping sand, boron, and lead onto the burning reactor.

It was on April 26, 1986, that the explosion of the main reactor in Chernobyl, Ukraine—then part of the Soviet Union—took place. A reactor systems test got completely out of control and resulted in the explosion and fire of Unit 4. Tons of highly radioactive material were released into the atmosphere, contaminating nearby towns and eventually drifting over the rest of the Soviet Union and into Europe. A total of 28 workers at the plant died of radiation poisoning in the first four months; close to 335,000 people were evacuated from the most heavily contami-nated areas. Cleanup activities eventually required 600,000 workers.

The triple meltdown at Fukushima Daiichi’s reactors happened on March 11, 2011. Japan was hit by a 9.0-magnitude earth-quake that rocked the country for almost six minutes. The impact of this was so phe-nomenal that the country’s main island was moved 2 meters east. The ensuing tsunami created 40-meter-high waves that would devastate the region: 20,000 people died or went missing; hundreds of thousands lost their homes. But it didn’t stop there: The worst-ever earthquake to hit Japan also caused the worst-ever nuclear disaster in the history of the country. The tsunami caused the Fukushima Daiichi plant—situated on the east coast of the island, the worst hit—to completely lose power to cool the reactors. The emergency power generators flooded. The fuel rods began to melt down and leak radiation into the surrounding area.

These events had some things in com-mon: Both became level 7 nuclear crises, the highest possible level on the international scale used to evaluate the seriousness of nuclear incidents, and both had catastrophic consequences. But there are many signifi-cant differences too. In terms of exposure

to radiation, Chernobyl released about 10 times the radiation that was released during Fukushima: A whole reactor exploded, creat-ing a massive radiation cloud that dispersed over a vast area in the center of the conti-nent. Because there was no containment structure around the plant, the radiation es-caped more freely. By contrast, in Fukushi-ma much of the radioactive cloud was blown out to sea thanks to the prevailing winds.

The causes of the incidents were also very different. The Chernobyl disaster was attributed to faulty reactor design, human error, and violation of procedures. Techni-cians had disabled critical safety systems for an unauthorized experiment. In the case of Fukushima, it was an extreme event that was impossible to predict.

This raises an important safety ques-tion: How do you plan and prepare for the unknown and the unpredictable? You can evaluate the likelihood that a critical valve or pipe will fail or break down and create a protocol around that. But how do you create response mechanisms for events so extreme and external in nature, such as a tsunami? When planning where or how to build a nu-clear facility, should we plan and prepare for earthquakes, tsunamis, or the likelihood of meteorites hitting Earth?

I don’t doubt that scientists and engi-neers could come up with answers and rec-ommendations to all these questions. The issues are of course going to be difficulty of managing increased costs and implemen-tation challenges and making nuclear a less attractive proposition by tightening regula-tions; e.g., think about increasing emergency planning zone sites and exclusion zones and evacuating or sheltering people. Where do you draw the line when assessing the vulner-ability of a plant?

Nuclear’s vulnerability

Views expressed on this page are those of the author and not necessarily those of ACS.

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 3

Reactions▸ Letters to the editor

Talking organic chemistry “Overwhelmed by Orgo” ( C&EN, March 28, page 24) on the crisis in organic chemistry education struck a chord. As an organic chemistry instructor at the university level for more than 20 years, I can attest to a no-ticeably diminished student capacity to han-dle the subject with each passing semester.

It should be emphasized, however, that organic chemistry is not and was never intended to be an easy discipline to master. Hand-wringing over new teaching tech-niques or providing yet another clone of the texts is an exercise in futility. Jazzing up texts with pictures and graphics does little more than inflate already obscene prices.

My suggestions to include at least a rudi-mentary introduction to organic chemistry in the preparatory general chemistry cur-ricula have been met universally with stiff resistance. As a result, students are thrown into the deep end with no swimming lessons.

But the core problem is endemic to science education in general. Students go unchallenged through their first 12 years of formal education, rewarded exclusively by rote memorization with no opportunity to develop skills in critical thinking and prob-lem solving by analogy, essential elements of organic chemistry. Disturbingly, many of those considered successful at the university level are so only because rote memorization is now embraced by their professors as well. Robert G. Davis Naugatuck , Conn.

It was interesting to read about the growing “overload of information” that is challeng-ing students of organic chemistry. Indeed, this issue of “big data” is being felt across the sector. Chemists—from education, to

How to reach us Chemical & Engineering News Letters to the Editor Our e-mail address is edit.cen@acs.org. Our fax number is (202) 872-8727. Comments can be left at cen.acs.org or via social media. Or you can send your letter to:C&EN Editor-in-Chief1155—16th St., N.W.Washington, DC 20036 Letters should generally be 400 words or fewer and should include the writer’s full name, address, and home telephone; letters and online comments may be edited for purposes of clarity and space. Because of the heavy volume of mail received at C&EN, writers are limited to one letter in a six-month period.

N E W V E R S I O N !

Over 100 new features & improvements in Origin 2016!

FOR A FREE 60-DAY EVALUATION, GO TO ORIGINLAB.COM/DEMO AND ENTER CODE: 8467

20+ years serving the scientific & engineering community

Over 500,000 registered users worldwide in: ◾ 6,000+ Companies including 120+ Fortune Global 500◾ 6,500+ Colleges & Universities ◾ 3,000+ Government Agencies & Research Labs

research, to industry—all need access to a multitude of different facts from myriad sources. But even though chemists have the option today of using numerous different tools to search sources, access to data is meaningless unless search results present relevant data that help to reveal insights. Never has the phrase “quality over quanti-ty” been more appropriate.

Chemistry, particularly inorganic chem-istry, is a highly complex area of science. For search tools to be useful to students, they must not only be able to act as a repos-

4 C&EN | CEN.ACS.ORG | APRIL 18, 2016

To read the bemoaning that nothing has changed for 50 years in organic chemistry textbooks coupled with the announcement that “we need … a different approach” was stunning. Instead of looking into a mirror, “hand-wringing” about organic textbooks took center stage at the symposium that C&EN reported on.

Textbook publishers are in the business of maximizing profits; educators are eth-ically responsible for providing their best grasp of teaching methods having the best evidence-based chance to maximize learn-ing. To think that a discussion focused on texts is a serious consideration of whatever ills exist in organic instruction is nonsense.

I taught general and organic chemistry throughout my career. I worked at it. For or-ganic, conscious decisions were made with colleagues about how to enhance student learning, and those efforts were critiqued. Text accoutrements were not important.

If any teacher supposes that having stu-dents sit and dangle their feet in the deep end of a swimming pool with texts stacked around them will teach them to swim, the educational enterprise is doomed. Rita Hessley Cincinnati

itory for huge amounts of data, but also be able to curate, analyze, filter, and present the exact piece of information required back to the user. Databases and search tools must therefore be able to contextualize and classify information and make links between data sources that add real value to a chemist’s work: for example, by com-bining experimental chemical data with published literature to provide rapid access to required facts.

Chemistry has the power to change the universe that we live in for the better. It’s imperative that the chemistry community does all it can to ensure students have ac-cess to the right data, at the right time. This will empower the next generation of chem-ists to further their knowledge and help them realize the value of the information at their fingertips. Thibault Geoui Frankfurt

In C&EN’s article, Melanie Cooper, a chem-istry education professor at Michigan State University, states, “Students come out of general chemistry typically very unpre-pared.” Worse, I’ve found, they graduate college very unprepared.

I routinely give a 12-question chemistry quiz to interviewees/applicants looking for employment as a bench chemist. I have found that they and even some recent hires are poorly prepared for jobs in chemistry. For instance, they cannot explain the differ-ence between a weak acid and a dilute acid or the difference between an end point and an equivalence point.

One interviewee, prior to taking my short chemistry quiz, told me he tutored chemistry, but he only got 6.5 correct an-swers out of 12. And a recent graduate with a B.A. in chemistry whom I had hired, and who has thankfully left, didn’t know that mercury was a liquid.

Who lets these people graduate high school or college? Educators should be held liable for poorly educating students. Some teachers are “teaching-disabled.” If you really want to improve the quality of chem-istry students going into the working world, put pressure on the secondary schools and colleges to stop graduating those who simply put in four years. The education and work ethic are not there. Fred G. Schreiber Newark , N.J.

“Overwhelmed by Orgo” highlights a chron-ic teaching/learning issue but unfortunately offers little in the way of solutions.

One reason general chemistry courses have fared better than organic chemistry courses is due to the use of graded problem

sets by many general chemistry instructors. Suitable problems, particularly quantitative ones, are provided in most textbooks. In four decades of teaching orgo, I have found that graded problems are also remarkably effective in fostering learning in organic chemistry. However, effective problems are more difficult to construct for a largely qual-itative subject, and I have found it necessary to prepare my own, rather than rely on the pedestrian array available in most textbooks.

A major reason instructors do not give problem sets in orgo is tradition. Tradition acts as a straitjacket in choice of textbooks, with generation after generation of in-structors choosing to teach exactly as they were taught, by the hoary functional group approach. I fear that traditionalist faculty, who typically had no problem learning orgo themselves, will continue to resist pedagogi-cal reorganizations that might make learning easier for legions of orgo students. Homer A. Smith Jr. Suffolk, Va.

Perhaps ACS’s Division of Organic Chemis-try or Committee on Professional Training can create a committee to produce rec-ommendations about what a new organic course should contain. We have to do some-thing for the sake of our students, and now might be a good time to do it. Jerry A. Hirsch Longmeadow, Mass.

▸ From the Web

Join the conversation. facebook.com/CENews

@cenmag

Use of the word “orgo” in Bethany Halford’s story about organic chem-istry education brought up some strong feelings in readers. So much so that detractors and defenders of the word took to C&EN’s website to voice their opinions. Some of their comments are highlighted below, as are the results of a Twitter poll conducted by fellow C&EN reporter Jyllian Kemsley (@jkemsley) gauging public perception of the word.

http://cenm.ag/orgocrisis

Please, do not ever shorten “organic” or “organic chemistry” to “orgo.” I cringed every time I saw that in the article and almost stopped reading it. Gail Shelly via C&EN’s website

“P-chem” is physical chemistry, “o-chem” or “orgo” is organic chem-istry, “gen-chem” is general chemistry ... deal with it.Rick Venegas via C&EN’s website

I do not think shortening “organic chemistry” to “orgo” is an affront to the subject but rather simply recog-nizes that is what probably 99% of college students call it. Crystal Baus via C&EN’s website

Using the term “orgo” disrespects the discipline. Sounds like a monster (ogre? orc?) from Middle Earth and could be considered an affront. Jeff via C&EN’s website

Re: ‘orgo’ as shorthand

'Orgo' as shorthand for 'organic chemistry'?

* Total Twitter respondents: 166

Ban it46%

Meh28%

Use it26%

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 5

Selections from the scientific literature and news from the week

▸ HighlightsConcentratesIV

AN

PO

PO

V (

AL

L)

An international research team has pre-pared a set of lanthanide antimony clusters that represent the first isolable compounds containing an all-metal antiaromatic ring. The achievement continues to expand the concept of aromaticity beyond its humble beginnings 150 years ago.

Researchers including Xue Min and Zhong-Ming Sun of Changchun Institute of Applied Chemistry and Ivan A. Popov and Alexander I. Boldyrev of Utah State Univer-sity created a series of anions, [Ln(Sb 4 ) 3 ] 3– , where Ln is La, Y, Ho, Er, or Lu. They made the anions by treating lanthanide benzyl complexes with the Zintl cluster complex K 5 Sb 4 in pyridine solvent and then isolating the anions as potassium cryptand salts.

On the basis of X-ray crystal structures and computational bonding analysis, the team says the rhombic Sb 4 rings that serve as ligands to the lanthanide metals are antiaromatic (Angew. Chem. Int. Ed. 2016, DOI: 10.1002/anie.201600706 ).

The concept of antiaromaticity has a storied history. In 1865, German chemist August Kekulé proposed the concept of aromaticity to explain the unusual proper-ties of benzene, a planar carbon ring that exhibits high stability and low reactivity. In 1931, German chemist Erich Hückel added to the definition that aromatic compounds have a delocalized 4 n + 2 π -electron sys-tem. In 1965, on the centennial of Kekulé’s proposal, Columbia University’s Ronald Breslow proposed the idea of antiaroma-ticity—the antonym of aromaticity—to characterize planar carbon rings with a 4 n π -electron system that exhibit low stability and high reactivity.

Aromaticity and antiaromaticity were

originally thought to be purely the do-main of organic chemistry. But during the past 20 years, chemists have shown that this organic boundary is flexible . In 1995, Gregory H. Robinson and coworkers of the University of Georgia isolated the sodium salt of a phenyl-substituted Ga3 ring with two π electrons, introducing the concept of metalloaromaticity.

In 2003, Boldyrev’s group in collabora-tion with Lai-Sheng Wang , now at Brown University, followed suit by reporting Li 3 Al 4

–, which includes an antiaromatic Al 4 4–

ring containing four π electrons. However,

the gaseous mole-cule was created in a laser-based experiment and couldn’t be trapped in a condensed state.

With the [Ln(Sb 4 ) 3 ] 3– series, chemists now have the first examples of isolable inor-ganic antiaromatic compounds. As a key feature, each Sb 4 ring stabilized by the lanthanide metal has four de-localized π electrons. The Sb 4 unit is anal-ogous to cyclobutadiene, Boldyrev says, which is the quintessential antiaromatic organic compound.

“Antiaromaticity in these all-metal sys-tems is very nice,” Breslow tells C&EN. “It is gratifying to see that our proposal, which was quite unexpected when we first made it for organic systems, has such generality.”

Further advances of aromaticity and antiaromaticity into metal territory will be valuable for understanding the properties of metal clusters, bulk metals, and alloys, Boldyrev and Sun add, which could be handy for making thin-film electronic materials.

“From a conceptual perspective, this is another example of the concept of aro-maticity—in this case antiaromaticity or antimetalloaromaticity—being extended beyond the realm of carbon,” Robinson says. “More important, taking all of this work into consideration, aromaticity and metalloaromaticity seem to be founda-tional principles throughout the whole of chemistry.” — STEVE RITTER

Compounds containing an all-metal antiaromatic ring have been isolated for the first time

Pushing the aromatic boundary CHEMICAL BONDING

New close-up views of the nuclear pore complex 7 Safety starts with school leaders, report says 7Drugs in treated wastewater can persist in produce 9A new route to functionalized cyclopropanes 10Nanowire LEDs fl ex and shine white light 11Dutch government investigates former DuPont facility 12Lawn care fi rm Scotts to stop using neonicotinoids 12Biodiesel growth spawns new catalyst makers 13Lead levels remain high in Flint’s water 16C&EN attends the 2016 White House Science Fair 16

Computational bonding analysis predicted this set of bonds for the new [Ln(Sb4)3]3– compounds.

In the [Ln(Sb4)3]3– compounds, a lanthanide(III) cation coordinates three antiaromatic Sb4 rings.

Rapid publication of energy capture, conversion, and storage research

ACS Energy Letters is accelerating the speed of energy research. What advances will it open up for you?

Now Accepting SubmissionsPublishing Issue 1 in Summer 2016

pubs.acs.org/acsenergyletters

Editor-in-Chief

Prashant V. KamatUniversity of Notre Dame

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 7

New views of the nuclear pore complex

STRUCTURAL BIOLOGY

Presidents and chancellors of U.S. univer-sities must take personal responsibility for changing the lab safety culture in academia, a new report says.

The document, published by the Associ-ation of Public & Land-Grant Universities (APLU), also lays out core values for a cul-ture of safety. It challenges top university officials to create high-level committees re-sponsible for lab safety, to modify tenure and promotion requirements to include safety, and to promote open communication about accidents and near misses on campuses.

APLU and the Association of American Universities additionally sent letters to lead-ers of more than 260 top U.S. universities calling on them to change the safety culture at their universities.

“We took it upon ourselves to really step up and say to the academic community that we need to own this,” says the University of Tennessee’s Taylor Eighmy, cochair of the

committee that authored the report. Most of the report’s 20 recommendations

have been made before by commissions organized by the National Academy of

Sciences , the Chemical Safety Board , and the American Chemical Society , which publishes C&EN.

What makes the APLU guide new is that “there was never really a process that was put together to collect, map, and reference all of the things that are needed to change a culture of safety,” Eighmy says. Each recom-mendation includes citations to previous reports and a list of best practices.

The APLU report “does a better job of making it clear that the faculty are responsi-ble for the safety of the work they supervise and that the chief honcho of the campus is ultimately responsible,” says Neal Langer-man, founder of the company Advanced Chemical Safety.

In particular, adopting the suggestion that safety become part of tenure and promo-tion decisions “would change the ball game completely,” Langerman says. — ANDREA WIDENER & JYLLIAN KEMSLEY

APLU issues recommendations to help universities improve their safety culture

Safety starts with school leaders, report says LAB SAFETY

JA

N K

OS

INS

KI

Science Concentrates

As gatekeeper of the cell’s nucleus, the nuclear pore complex (NPC) controls the shuttling of thousands of different proteins, RNA molecules, and nutrients between the nucleus and surrounding cytoplasm. Built from more than 30 types of nucleoporin proteins, and with a mass of more than 100 million daltons and a width of 1,000 Å, the NPC’s gargantuan, membrane-embedded structure has long stymied structural biologists.

Two research teams working indepen-dently have now reported the overall archi-tecture of this mega transport machinery nearly down to the amino acid residue level.

Taking a top-down approach, a team led by Martin Beck of the European Molecular Biology Laboratory used cryo-electron mi-croscopy, mass spectrometry, and computer

modeling to determine the location of hun-dreds of nucleoporin proteins in the human NPC ( Science 2016, DOI: 10.1126/science.aaf0643 ).

Meanwhile, a team led by André Hoelz of Caltech took a bottom-up approach to solve the crystal structure of fungal nuc-leoporin proteins containing a total some 320,000 amino acid residues ( Science 2016, DOI: 10.1126/science.aaf1015 ). With the help of protein-protein interaction data, the team then docked those proteins into a previously published, lower resolution cryo-electron microscopy NPC structure.

Despite the different approaches and dif-ferent organisms, the two teams converged on the same overall eightfold symmetrical NPC architecture. “It’s amazing that evo-lution maintained the same overall folds in

organisms as different as humans and fungi,” Hoelz says.

The pair of papers piqued the interest of Durham University’s Martin Goldberg. “They appear to be exciting, comprehen-sive, and ambitious, with potentially novel insight,” Goldberg comments. But it will take careful scrutiny of the structural details—and there is a wealth of details—to capitalize on the work, he notes.

“Now that we understand the overall architecture, we need to focus on how it ac-tually works,” Beck says. One way to do that, he adds, is by studying the peripheral pro-teins and protein complexes that associate with the NPC and regulate the translocation of cargo. The Hoelz team is interested in studying how viruses shut down the NPC’s transport capabilities to co-opt their host’s ribosomes in the cytoplasm to produce viral proteins without any competition from endogenous mRNA. — SARAH EVERTS

Two studies bring the architecture of the cell’s mega transport machinery into better focus

APLU’S core values for a culture of safety

▸ Safety is everyone’s responsibility. ▸ Good science is safe science. ▸ Safety training and safety education are

essential elements of research and education. ▸ An improved culture of safety is

necessary to truly reduce risk throughout the academic enterprise.

▸ It is best to recognize that diverse methods and flexible approaches will be used by each institution to develop a strong culture of safety, unique to its situation.

Note: To learn how some educators are teaching hazard assessment, turn to page 26 of this issue of C&EN.

Structure of the nuclear pore

complex, the main transport machinery

in and out of the nucleus. The pore is

about 1,000 Å across.

8 C&EN | CEN.ACS.ORG | APRIL 18, 2016

AN

GE

W.

CH

EM

. IN

T.

ED

.

Science Concentrates

Because nitric acid (HNO 3 ) is stable, long-lived, and not photochemically reactive, it’s long been thought to be the final desti-nation for reactive nitrogen species in the atmosphere. But that assumption might be wrong.

A team led by Xianliang Zhou of the New York State Department of Health and the University at Albany, SUNY, proposes that nitric acid in the at-mosphere gets quickly recycled back into nitrous acid (HONO) and other forms of nitrogen oxides (NO x ) via photochemical reactions involving nitrate in aerosol particles ( Nature 2016, DOI: 10.1038/nature17195 ).

Nitrogen oxides are involved in the formation of ozone in the atmosphere. The findings could lead to atmospheric chemistry models with improved estimates of nitrogen species and ozone.

In the study, Zhou and coworkers performed airborne and lab-based mea-surements of samples from the marine boundary layer, the portion of the atmo-sphere in direct contact with the ocean.

In field measurements obtained during flights over the North Atlantic Ocean, the researchers detected HONO concentra-tions of about 10 parts per trillion. That may not sound like a lot, but HONO rapid-

ly undergoes photochemical reactions so there must be some source producing the acid, Zhou says.

In those field measurements, the team found no correlation between HONO and NO x , a possible precursor of HONO. Instead, they found a correlation between

the concentrations of HONO and nitrate in aerosol particles.

To test whether HONO could indeed come from particulate nitrates, the team ran photochemical experiments with aero-sol samples back in the lab.

“Our results show there’s a rapid photo-chemical recycling process that converts nitric acid and particulate nitrate into more reactive species like HONO and NO x ,” Zhou says. “If you’re over land, you have many NO x sources, so the recycling is not as dominant. But if you go to a re-

mote area where the emission source is really low, then the recycling process

becomes more obvious and more important.”

“Measurements of NO x that my group has been making over the

past 10 years have been consistently higher than those that are predicted

by models,” says James Lee, an atmospheric chemist at the University of York, who makes

atmospheric measurements in remote parts of the Atlantic. “This recycling mechanism has the potential to reconcile this.” He says this finding is important be-cause increased NO

x in remote areas could

signal more ozone production. — CELIA ARNAUD

Photochemical reactions could lead to source of ozone-forming nitrogen oxides

New fate for atmospheric nitric acid ATMOSPHERIC CHEMISTRY

To diagnose conditions such as sleep apnea, doctors monitor patients’ res-piration rates with devices that can be cumbersome and expensive. George M. Whitesides and coworkers at Harvard Uni-versity have now developed an inexpen-sive, lightweight paper-based alternative ( Angew. Chem. Int. Ed. 2016, DOI: 10.1002/anie.201511805 ).

To make the device, the research-ers print graphite electrodes on paper, which they incorporate into a cloth surgical mask. When the paper absorbs water, the conductivity of the electrodes changes. Because exhaled breath con-tains more water than inhaled breath, the sensor can measure respiration rate from transient changes in moisture con-tent. The team connects the sensor to a

battery-powered reader that digitizes the elec-trical signal and wire-lessly transmits the sig-nal to a tablet running a data analysis app.

They used the device to measure respiration rates in individuals at rest as well as during light ex-ercise such as walking and more vigorous exercise such as climbing several flights of stairs.

The current design can run for about nine hours on a single battery charge, which should be long enough to monitor a full night’s sleep. The paper sensor and mask should be cheap enough for sin-

gle-use applications. The researchers sug-gest that the best use for the sensor in the near term will be for characterizing sleep apnea. — CELIA ARNAUD

Paper sensor measures respiration rate DIAGNOSTICS

Rate:

15 /minAmplifier and signal

processing unit

Tablet with

analysis app

bletletletletletletlet wi wi

Wireless

Bluetooth

connectionconnectio

Mask with

breath sensor

Mask wk wk wk wk with

A paper sensor embedded in a mask measures respiration rate and sends the signal for processing and display.

XONO2

XONO2

RONO2RONO2

NO2

HNO3

HONO + Light

ParticulateNO3

O2

O3Light

Light

Light

RO2

HO2

XOOH

OH

OH + NO

X = Br or IR = organic groupAerosol particle

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 9

SH

UT

TE

RS

TO

CK

R is a carbon-based group, X – is an anion, PC is a photocatalyst, PC* is a light-activated version, and PC

red is a reduced form.

Many natural products, pharmaceuticals, and other biologically active molecules feature chiral carbon atoms attached to four other carbons. Chemists can synthe-size these quaternary stereocenters using organometallic reagents that add carbon groups to conjugated carbonyl compounds. These reagents, however, are expensive and hard to generate, can cause problematic side reactions, and don’t always work well at crowded carbon centers.

Now researchers report the first radical route to quaternary carbon stereocenters, offering a possibly easier way to form the important chiral groups.

Chemists previously have tried using radical-based conjugate addition reactions to form chiral quaternary centers because, compared with organometallic reagents, radicals are cheaper and easier to produce, readily add carbons to sterically congested carbon sites, and cause less-problematic side reactions. But these radical reactions

have not worked. For example, amine-cata-lyzed radical conjugate additions have been hampered by the formation of an unstable radical cation intermediate.

Paolo Melchiorre of the Institute of Chemical Research of Catalonia and co-workers have now found a way around that problem. In their amine-catalyzed reaction, they trap the unstable radical and prevent its

breakdown. The result is the first enantiose-lective, catalytic, radical conjugate addition to generate quaternary carbon stereocenters ( Nature 2016, DOI: 10.1038/nature17438 ).

In the reaction, an organocatalyst’s amine group reacts with an enone starting material to produce a chiral iminium cation. A nuc-leophilic radical carbon group then adds to the molecule’s carbon-carbon double bond, forming an unstable radical intermediate. A redox-active carbazole group on the organo-catalyst immediately reduces the unstable intermediate, preventing it from breaking down. The reduced intermediate then tautomerizes, changing how its atoms are connected, to form a species that is further reduced and hydrolyzed, yielding the qua-ternary product and releasing the original organocatalyst. A separate photocatalyst both creates the nucleophilic radical and catalyzes the final reduction.

“Since this method provides a conve-nient route to quaternary stereocenters

with the potential of excellent functional group tolerance, I envision a wide range of applications,” comments radical-con-jugate-addition expert Steven L. Castle of Brigham Young University. Although the study demonstrated its use on a limited range of substrates, “it should be possible to extend the scope to encompass a broader range.”— STU BORMAN

Chemists deal with unstable intermediate to develop first radical route to chiral quaternary carbons

Radical pathway to four-way carbons

CATALYSIS

Enonestartingmaterial

O

Chiraliminium cation

H +N

X–

NH2

Chiral amineorganocatalyst

O

R

Quaternaryproduct

N

R

Imine-organocatalyst

conjugate

Reduction

PC PCred

Hydrolysis

H2O

N

R

Imine radical cation

X–+•

Tautomerization HN

R

Enamineradicalcation

X–

+•

Electrontransfer

Imineformation

PC*

PCred

Radical addition

R–H

RLight

PC

H +N

X–

R

Intramolecularreduction

Unstable iminiumradical cation

With freshwater resources dwindling worldwide, the practice of using treated wastewater to irrigate crops is growing. But that practice might have a downside: In a new study, peo-ple who ate vegetables grown using such reclaimed water had increased urine levels of carbamazepine, an antiepileptic drug commonly detected in wastewater ( Environ. Sci. Technol. 2016, DOI: 10.1021/acs.est.5b06256 ).

The randomized, controlled study is the first to directly address human exposure to such pharmaceutical contaminants via produce, says Ora Paltiel of the Hadassah-Hebrew Uni-versity of Jerusalem.

Paltiel and her colleagues gave 34 healthy volunteers batches of pro-duce to eat for a week—either vege-tables grown with reclaimed water or organic vegetables grown with only freshwater.

Before the study began, some vol-unteers had quantifiable concentra-tions of carbamazepine in their urine while others didn’t. This remained true for participants after a week of eating the organic produce. But after a week of eating produce grown with reclaimed water, every subject ex-creted detectable levels of the drug.

“This fits what we’ve all suspected but have not shown experimentally,” says Alistair Boxall of the University of York. Although the urine levels were very low—four orders of magni-tude lower than those from patients actually taking the drug—people who eat a lot of produce will be exposed to such contaminants throughout their lifetimes, he adds. — ALLA KATSNELSON, special to C&EN

Exposure to pharmaceutical contaminants via vegetables

FOOD

10 C&EN | CEN.ACS.ORG | APRIL 18, 2016

2-D MATERIALS

▸ Sniffing single molecules with graphene

Electronic sensors can now sniff out single gas molecules by using graphene, according to a research team from the Japan Advanced Institute of Science & Technology ( Sci. Adv. 2016, DOI: 10.1126/sciadv.1501518). Graphene has previously shown itself capable of single-molecule sensitivity, but this earlier feat required

ORGANIC SYNTHESIS

▸ Gold catalysis with less fuss

In an advance that simplifies gold redox catalysis, a research team led by A. Stephen K. Hashmi of Heidelberg University, in

PHYSICAL CHEMISTRY

▸ Single-atom heat engine created

A German team has fulfilled a prediction made decades ago by physicist Richard Feynman: a heat engine composed of a single atom ( Science 2016, DOI: 10.1126/science.aad6320). Heat engines, which convert thermal energy to mechanical work, have been used in various forms for several hundred years. Over the past de-cade, scientists have designed ever-small-er heat engines, with the smallest being composed of a single molecule. Now, the German team, led by Kilian Singer of

the University of Kassel and Johannes Rossnagel of the University of Mainz, has trapped a calcium ion ( 40 Ca + ) and alter-nately cooled and heated it with lasers and electric fields. The temperature differenc-es produced by heating and cooling caused the atom to oscillate harmonically in an axial direction, “similar to the flywheel of a mechanical engine,” the authors say. They envision a wide variety of future ap-plications, such as single-atom refrigera-tors and pumps. — ELIZABETH WILSON

ORGANIC SYNTHESIS

Cyclopropanes built by trimerization Among synthetic methods available to chemists, cyclotrimerization reactions are an efficient approach to assembling complex cyclic molecules in a single step from three simple building blocks. One limitation of the process is that

known examples only allow synthesis of aromat-ic or heterocyclic compounds, such as the [2+2+2] cyclotrimerization of alkynes or acetophenones to make substituted benzenes or of aldehydes to make trioxanes. Srimanta Manna and Andrey P. Antonchick of the Max Planck Institute of Molecular Physiology have now expanded the cyclotrimerization strategy to make cyclopropanes ( Angew. Chem. Int. Ed. 2016, DOI: 10.1002/anie.201600807). The team stitched together a variety of substituted acetophenones (one example shown) using a copper iodide/2,2´-bipyridine catalyst and a peroxide oxidant. The [1+1+1] cascade reaction proceeds through a previously unknown radical pathway in which a copper enolate intermediate functionalizes unactivated C–H methyl bonds of two acetophenone molecules to form a diketone. The diketone subsequently couples with a third acetophenone molecule leading to the cyclopropane ring. Overall, the new method is counter to the way chemists typically think about making cyclopropanes from olefins. — STEVE RITTER

MIZ

UT

A L

AB

/JA

IST

(G

RA

PH

EN

E S

CH

EM

AT

IC);

CO

UR

TE

SY

OF

JO

HA

NN

ES

RO

SS

NA

GE

L (

HE

AT

EN

GIN

E)

high magnetic fields. Now, researchers have observed single carbon dioxide molecules with a graphene-based sensor that operates at modest, readily supplied voltages. This work could lead to compact, highly sensitive devices for personal envi-ronmental monitoring, says team member Jian Sun. Sun and his colleagues developed their sensor using an unorthodox archi-tecture. Usually, graphene in a sensor lies flat on a substrate, the team says. In this geometry, however, interactions between graphene and its support can mask inter-actions between graphene and gas mol-ecules. So the researchers angled a two-atom-thick graphene ribbon between two

3

CuI/2,2́ -bipyridine,peroxide

–6HF F

F

O

OO

F

O

electrodes at different heights to lift the ribbon away from its silicon dioxide sub-strate. When a voltage is applied between the electrodes, each adsorbed CO 2 mol-ecule scatters electrons in the graphene, creating discrete but discernible changes in its resistance, the team reports. — MATT DAVENPORT

Radio-frequency electrodes (silver) heat this trapped calcium ion (blue), which is the core of a single-atom heat engine.

Science Concentrates

Adsorbed CO 2 gas molecules scatter

electrons in a graphene film, bumping up its resistance.

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 11

NATURAL PRODUCTS

▸ Fungi make isoquinolines

By peering at a mysterious biosynthetic gene cluster in the common compost heap fungus Aspergillus fumigatus, a team of re-searchers led by Cornell University’s Frank C. Schroeder and Nancy P. Keller of the Uni-versity

NANOMATERIALS

Nanowires keep white LEDs flexible Flexible light-emitting diodes allow designers to create wearable displays, flexible screens, and bendable biomedical devices. Today’s best technology for flexible light sources is organic LEDs. But OLEDs have relatively short lifetimes,

and bright ones aren’t very energy efficient. Now, researchers have shown the potential to overcome those limitations by building flexible white LEDs out of a more robust, efficient inorganic semiconductor—gallium nitride ( ACS Photonics 2016, DOI: 10.1021/acsphotonics.5b00696). Joël Eymery of France’s Alternative Energies & Atomic Energy Commission; Maria Tcherny-cheva of the University of Paris, Saclay; and colleagues grew GaN nanowires on a sapphire substrate and embedded them in polydimethylsiloxane laced with a commercially available phosphor, yttrium aluminum garnet doped with cerium. The team peeled the material from the substrate and sandwiched it between a sil-ver nanowire mesh and a thin metal foil, which serve as electrodes. The device’s conversion efficiency—the ratio of electrons in to photons out—reached 9.3%. That’s low, but flexible devices’ efficiencies don’t need to be as high as those of general lighting applications, Eymery says. The devices could be bent to a radius of 5 mm without any reduction in performance. — NEIL SAVAGE, special to C&EN

of Wisconsin, Madison, has discovered that the microorganism unexpectedly makes a variety of isoquinolines. Scien-tists long thought that these natural prod-

ucts—based on a heterocyclic scaffold composed of a benzene ring fused

to a pyridine ring—were produced primarily by plants. Isoquinolines

are incredibly useful scaffolds : Members of the family are

used as anesthetics,

Plant and fungi both build isoquinolines from the amino acid tyrosine through similar but evolutionarily independent mechanisms.

Bending this white-light nanowire LED does not impede its performance.

AC

S P

HO

TO

NIC

S (

FL

EX

IBL

E D

EV

ICE

)

Germany, has discovered a means for car-rying out visible-light-mediated reactions without the need for an auxiliary oxidant or a ruthenium or iridium photosensitiz-er. The additional reagents are typically needed to promote oxidation of gold(I) to gold(III) as part of the catalytic cycle. The Hashmi group determined that a phosphine gold(I) chloride catalyst can function as its own photosensitizer when irradiated with visible light. When paired with an aryldiazo-nium salt, the gold(I) species is oxidized to a gold(III) species that can complete the di-functionalization of alkynes to make α-aryl ketones ( Angew. Chem. Int. Ed. 2016, DOI: 10.1002/anie.201511487). What’s more, by using a P,N-bidentate ligand, the research-ers were able to isolate and obtain the X-ray crystal structure of the gold(III) species (shown above). Chemists have debated whether gold(III) intermediates are in-volved given gold’s high oxidation potential. The Heidelberg group’s effort provides the first direct evidence to satisfy that curiosity, and further studies show that the group’s approach is a general method for generating arylgold(III) complexes ( Chem. Commun. 2016, DOI: 10.1039/c6cc02199a). — STEVE RITTER

Arylgold(III) catalyst intermediate

Au

Cl

P

N

+

BF4–

Fumisoquin A

NH2

HON

OH O

HHO OH

Fungalpathway

NH2HO

O

OH

(S)-Tyrosine

CH3O

N

OH

H

OH

OCH3

(S)-Scoulerine

Plantpathway

vasodilators, antifungal agents, and dis-infectants. Researchers may want to mine other fungi—many of which also possess similar biosynthetic gene clusters as the one in A. fumigatus —for new, potentially useful isoquinolines or harness fungi to produce existing ones. The team found that the isoquinolines—called fumiso-quin A, B, and C—made by A. fumigatus were synthesized from the amino acid tyrosine, through a sequence of phenol hydroxylation, N-methylation , and oxida-tive cyclization steps reminiscent of plant isoquinoline biosynthesis ( Nat. Chem. Biol. 2016, DOI: 10.1038/nchembio.2061). However, the plant and fungal biosynthet-ic genes show no homology, suggesting that the ability to make these compounds evolved independently, yet settled on the same synthetic strategy—an example of convergent evolution. — SARAH EVERTS

12 C&EN | CEN.ACS.ORG | APRIL 18, 2016

SH

UT

TE

RS

TO

CK

(C

AN

AL

); S

CO

TT

S M

IRA

CL

E-G

RO

(P

ES

TIC

IDE

)

Business Concentrates

Scrutiny of the potential health impact of perfluorooctanoic acid (PFOA) is extending into Europe. Dutch government officials are looking into past use of PFOA at a former DuPont plant near the city of Dordrecht, where the chemical was employed starting in 1970. Chemours inherited the plant when it spun off from DuPont last year.

The Dutch government has ordered blood tests on Dordrecht residents to determine if

there is a link between health problems and PFOA, which was formerly used to make flu-orochemicals such as the nonstick material Teflon. PFOA can build up in the body and adversely affect the liver, impair the develop-ment of a fetus, and raise the risk of cancer.

It is likely that local residents were chron-ically exposed to higher amounts of PFOA than is safe, the Dutch National Institute for Public Health & the Environment concluded

in a recent report . “People living in the direct neighborhood of the DuPont/Chemours factory in Dordrecht have been exposed to PFOA by air for many years,” the institute said.

Dordrecht is Chemours’s largest pro-duction complex in Europe with more than 550 employees. The site also employs 350 DuPont staffers. Chemours continues to produce or blend fluorochemicals at the site.

Chemours faces a series of legal cases in the U.S. relating to PFOA exposure from its plant in Parkersburg, W.Va. The firm says it will “vigorously defend” itself against PFOA lawsuits.

In a separate case involving the Dordrecht plant, the Dutch TV program “EenVandaag” says it questioned 35 women who were in-volved in making spandex at the site. The program claims that 33 of them say they ex-perienced fertility problems.

A website for “EenVandaag” cites two Dutch chemists who point to potential ex-posure to N,N -dimethylacetamide, a solvent used in the production of spandex yarn. The European Chemicals Agency classifies the solvent as a substance of very high concern that “may damage the unborn child.”

DuPont says it will not comment on individual cases but tells C&EN it listens to employee concerns and has scheduled a meeting with the Inspectorate SZW, a Dutch agency with oversight of workplace safety, to discuss issues around spandex produc-tion. DuPont sold the spandex plant in 2004; it closed down in 2006. — ALEX SCOTT

Government to test residents living near former DuPont fluorochemicals facility

Dutch chemical plant under investigation

POLLUTION

Consumer lawn and garden care com-pany Scotts Miracle-Gro says it will stop using neonicotinoid-based pes-ticides in its Ortho brand products because of concerns over honeybee health. It will remove imidacloprid, clothianidin, and dinotefuran from its offerings by 2017.

“This decision comes after careful consid-eration regarding the range of possible threats to honeybees and other pollinators,” says Tim Martin, general manager of Ortho. “While agencies in the U.S. are still evalu-ating the overall impact of neonics on pollinator populations, it’s time for Ortho to move on.”

EPA is conducting risk assessments of the pesticides and has temporarily stopped granting new permits for their use.

Neonicotinoid pesticides were developed by Bayer in 1985 and pro-moted for their species specificity, relatively low toxicity, and effective-ness in small quantities. But con-cerns about colony collapses among honeybees and other pollinators have prompted researchers to study unintended effects on nonpest spe-cies. Bayer and other manufacturers defend the pesticides’ safety and use.

A year ago, the retail chain Lowe’s said it would phase out products con-taining neonicotinoids. Last month, Maryland passed a bill banning consumers from purchasing the pes-ticides. Scotts says it is working with the Pollinator Stewardship Council, an advocacy group, to encourage the government to allow labeling of non-neonicotinoid products.

Honeybee advocates hailed the announcement. “We are glad to see that Ortho is moving away from using these bee-toxic chemicals, and we hope that other garden and nursery companies will follow suit,” says Larissa Walker, pollinator pro-gram director at the Center for Food Safety. — MELODY BOMGARDNER

Scotts nixes neonicotinoids

AGRICULTURE

$164 billionChemical industry investment in the U.S. linked to plentiful shale gas and natural gas liquids, according to the American Chemistry Council. The money will go to 264 new facilities, expansions, and plant re-starts; 40% of the work is completed or under way, the trade association says.

BY THE NUMBERS

Residents living in Dordrecht will be tested for exposure to PFOA.

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 13

Capitalizing on continued drug industry interest in CRISPR/Cas9 technology, the gene-editing therapy start-up Intellia Therapeutics has formed a new partner-ship and is preparing for an initial public offering (IPO) of stock.

Last week, Cambridge, Mass.-based In-tellia signed a licensing and collaboration deal with Regeneron Pharmaceuticals. The partners will develop both the underlying CRISPR/Cas9 technology and in vivo ther-apies against as many as 10 targets. About half the targets will be diseases—such as the protein-accumulation disorder trans-thyretin amyloidosis—that may be treated by editing genes in the liver.

Regeneron will pay $75 million up front as well as potential milestone payments. In addition, Regeneron has agreed to invest up to $50 million in Intellia’s next equity financing. Intellia’s other drug in-

dustry investor is Novartis, which collab-orates with the biotech firm in the areas of chimeric antigen receptor T cells (CARTs) and hematopoietic stem cells.

Meanwhile, Intellia, which is a 2014 spin-off of the CRISPR/Cas9 technology firm Caribou Biosciences, has filed to sell up to $120 million worth of stock. If it goes ahead with an IPO, it will be the second CRISPR start-up to do so. In February, competitor Editas Medicine raised about $100 million through its IPO. Its shares are now trading at more than twice their offering price.

Whether Editas’s good fortune contin-ues and Intellia’s stock warrants a similar value is uncertain. The earliest clinical trials by either company are at least a year away. Editas is collaborating on CART therapies with Juno Therapeutics while a third CRISPR/Cas9 competitor, Crispr

Therapeutics, works with Bayer and Ver-tex Pharmaceuticals.

At the same time, the companies’ lead-ing scientists and founders are embroiled in a patent interference proceeding over rights to the basic CRISPR technology. Cowen & Co. stock analyst Phil Nadeau expects eventually to see multiple cross-licenses along with additional patents on individual therapies.

“The value in the CRISPR franchises will be determined by their ability to develop successful therapeutic products,” Nadeau told clients in a report. — ANN THAYER

Developer of CRISPR/Cas9 therapies taps into Regeneron and the stock market to support its pipeline

Intellia lines up a stock offering and new partner

START-UPS

Growth in the biodiesel market is spurring two small companies to invest in U.S. pro-duction of sodium methylate, a catalyst used to convert fats and oils into the re-newable fuel. These Davids will be going up against two biodiesel catalyst Goliaths, the German chemical makers BASF and Evonik Industries.

New Heaven Chemicals is starting up a plant in Manly, Iowa, that will make 18,000 metric tons per year of sodium methylate for biodiesel industry customers. Prasad Devineni, the firm’s director, says the plant is being commissioned and should be run-ning in the next few weeks.

Although New Heaven will be new to U.S. production, its parent company, India’s TSS Group, has been importing sodium methyl-ate from Saudi Arabia since 2006, Devineni notes. New Heaven anticipates building a second, similarly sized, sodium methylate plant in Houston.

Meanwhile, Interstate Chemical is advancing plans to produce sodium meth-ylate in Erie, Pa., to serve customers such as the nearby firm Hero BX, which calls itself the largest biodiesel maker east of the Mississippi.

Interstate says it will spend $60 million to build plants for sodium methylate and methanol, the latter of which is reacted with sodium hydroxide to make the cata-lyst. Interstate has been producing sodium methylate for close to 10 years using an older process that starts with sodium met-al. The firm’s plan to invest in the newer route follows DuPont’s decision to close

its sodium facility in Niagara Falls, N.Y. U.S. biodiesel consumption has enjoyed

a meteoric rise from less than 100 million L in 2004 to almost 8 billion L in 2015, accord-ing to the National Biodiesel Board. During those years, Evonik erected sodium methyl-ate plants in Alabama and Argentina. BASF built in Argentina and Brazil.

However, the years ahead may not be as heady for the catalyst newcomers. U.S. imports of biodiesel are on the increase. And a growing portion of biodiesel is so-called renewable diesel, which is made via a hydrotreating process that doesn’t require sodium methylate. — MICHAEL MCCOY

Seeing more growth ahead, two small companies invest in new plants

Biodiesel catalyst ranks to expand RENEWABLES

Pipeline Intellia is pursuing multiple targets with CRISPR/Cas9 edits

Source: Intellia

Alcohol

Sodium methylatecatalyst

R

O

R

O

R

O

OO

O

CH3OH+

Glyceride

3 CH3O R

O

+

Biodiesel

OHHO

OH

Glycerin

PROGRAMS PARTNER TYPE OF GENE EDIT

Transthyretin amyloidosis

Regeneron Knockout

α1-Antitrypsin deficiency

Proprietary Knockout, repair

Hepatitis B Proprietary Knockout

Inborn errors of metabolism

Proprietary Knockout, repair, insertion

Hematopoietic stem cells

Novartis,

proprietary

Knockout, repair, insertion

CARTs Novartis Knockout, insertion

14 C&EN | CEN.ACS.ORG | APRIL 18, 2016

INVESTMENT

▸ Alberta may get more polypropylene

Petrochemical Industries Co. of Kuwait and Pembina Pipeline are studying the construction of a propane dehydrogena-tion and polypropylene manufacturing complex in Alberta that would make up to 800,000 metric tons of the plastic per year. The companies hope to make their final decision by mid-2017 and open the plant by 2020. PIC is already active in Alberta through its Equate Petrochemical joint venture with Dow Chemical. Late last year, Williams Cos. unveiled plans to build a pro-pane dehydrogenation/polypropylene plant in Alberta with newcomer North American Polypropylene. However, Williams is now said to be considering a sale of its Canadian assets. —ALEX TULLO

SUSTAINABILITY

▸ Another Cl2 plant

to drop mercury

Another European chlor-alkali facility will phase out mercury-based production. The polyvinyl chloride maker Inovyn says it in-tends to convert its plant in Stenungsund, Sweden, from mercury to membrane technology by the end of 2017, which is the European Commission’s deadline for converting. Several firms, including Inovyn in Belgium, have made similar switches elsewhere. Inovyn continues to evaluate options for its plant in Spain, where the lack of competitively priced raw materials makes the investment less attractive, it says. —MICHAEL MCCOY

BIOTECHNOLOGY

▸ Two companies buy into personal care

Specialty chemical makers Evonik Indus-tries and Clariant are expanding their cos-metic active ingredient portfolios. Evonik has purchased Alkion Biopharma, an Impe-rial College London spin-off now located in Évry, France. Alkion obtains extracts from plant biomass cultivated in a lab. Clariant signed an agreement to acquire a 17% stake in BioSpectrum of South Korea. The fami-ly-owned firm makes cosmetic ingredients based on renewable raw materials. —MARC REISCH

OUTSOURCING

▸ Aesica doubles U.K. development site

With the opening of a new facility in Queenborough, England, the drug services firm Aesica Pharmaceuticals says it has doubled its drug product development

capacity. Aesica says the capabilities in the new facility allow it to develop and manufacture a customer’s product from early formulation development through clinical trials and into commercialization. The Queenbor-ough site can handle both highly potent and controlled substances, the company adds. —MICHAEL MCCOY

ANALYTICAL CHEMISTRY

▸ Büchi acquires Grace chromatography line

Büchi Labortechnik has acquired W.R. Grace’s portfolio of flash chromatography and evaporative light-scattering detector instruments. Grace built the business under Gregory E. Poling, who recently left to head GCP Applied Technologies, the construction and packaging business spun off of Grace. Büchi says it will integrate the Grace instruments into its chromatogra-phy portfolio. Grace will continue to pro-vide silica-based purification media to Bü-chi and other customers. —MARC REISCH

MERGERS & ACQUISITIONS

▸ Calgon Carbon buys Arkema business

Calgon Carbon will acquire Arkema’s Ceca activated carbon and mineral-based filter aid business for $160 million. The business had sales last year of $103 million and operates six plants in Europe. Pittsburgh-based Cal-gon, which calls itself the world’s largest pro-ducer of granular activated carbon, says the purchase will extend its geographic reach and take it into the adjacent filtration media

PETROCHEMICALS

Ineos is restarting a once-idle Grangemouth crackerIneos has completed successful operational trials on an idle ethylene cracker in Grangemouth, Scotland, in preparation for the arrival of seaborne ship-ments of ethane feedstock from the U.S. The cracker, one of two at the site, was mothballed in 2008. Blaming dwindling feedstocks from North Sea gas fields, the company nearly shuttered the entire Grangemouth complex in 2013. Instead, it opted to spend $2 billion on infrastructure to import ethane into Europe. “When U.S. shale gas finally arrives here in the autumn, this plant will move into the premier league of European petrochemical plants,” says Gordon Milne, Ineos’s Grangemouth operations director. The gas originates in western Pennsylvania and will be exported from Philadelphia. Last month, an ethane shipment arrived at an Ineos cracker in Norway. Other companies have been working on importing U.S. ethane including Saudi Basic Industries Corp. for its Teesside, England, cracker and Borealis for its Swedish facility. ExxonMobil will purchase imported ethane from Ineos next year for its eth-ylene plant in Mossmorran, Scotland. —ALEX TULLO

A view inside Aesica’s facility in Queenborough, England.

AE

SIC

A

market. Calgon makes activated carbon, a highly porous material, from coal. Ceca’s raw material is wood. —MICHAEL MCCOY

Business Concentrates

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 15

Business Roundup ▸ Chemtura will expand ca-

pacity for 4,4’-methyl enebis-2-chloroaniline-free polyure-thane elastomers in Latina, Italy, by the end of the year. MbOCA-containing com-pounds are being phased out next year under Europe’s REACH chemical regulatory regime.

▸ BASF has submitted the registration dossier for a new insecticide active ingredient to regulators in the U.S. and Canada. Licensed from the Japanese firm Meiji Seika Pharma in 2010, Inscalis be-longs to a new chemical class, pyropenes, that provides a

new mode of action against piercing and sucking insects.

▸ DRT, a French producer of pine-based chemicals, has broken ground in Effingham County, Ga., for what will be its first U.S. facility. The Pine Chemicals Association says the plant will be the first greenfield turpentine distill-ery built in the U.S. in half a century.

▸ Innovia Group has agreed to sell its cellophane business, including a plant in Wigton, England, to Japan’s Futamura Chemical for about $85 mil-lion. Futamura, which makes

plastic and cellulose films primarily for food packaging, says the business will expand its geographic reach.

▸ Evolva, a Swiss synthetic biology firm, has signed an R&D agreement with the U.S. Navy to create advanced materials. The work targets lightweight, fire-resistant composite materials for use in aircraft, ships, fabrics, vehi-cles, and construction.

▸ BASF has licensed a suite of nickel-containing cathode materials for use in lithi-um-ion batteries from CAMX Power. By delivering high en-ergy density and high power, the materials can extend the range of electric vehicles and

the time between charges for portable devices, CAMX says.

▸ Jellagen, a Wales-based start-up, has raised $2.2 mil-lion from private equity and government agencies to fund the scale-up of its technology to make medical-grade col-lagen from jellyfish. Medical applications include wound care, soft tissue repair, and bone grafts.

▸ Incyte will pay Eli Lilly & Co. $35 million for rights to commercialize ruxolitinib, a JAK1/JAK2 inhibitor Incyte de-veloped, for transplant-relat-ed graft-versus-host disease. Incyte already sells ruxolitinib as Jakafi to treat polycythemia vera, a blood cancer.

INFECTIOUS DISEASE

▸ Vertellus completes DEET expansion

Vertellus Specialties has completed an 80% expansion of capacity for the insect

repellent N,N-dieth-yl-m-toluamide (DEET) at its Greensboro, N.C., site. The expansion is intended to meet grow-ing demand prompted

by recent outbreaks of the mosquito-borne Zika virus. The Centers for Disease Control & Prevention just concluded definitively that the outbreak of microcephaly plaguing Brazil is caused by Zika. —MARC REISCH

DRUG DEVELOPMENT

▸ Amyris to revise artemisinin route

Industrial biotechnology firm Amyris will work to reduce the cost of making the malaria treatment artemisinin via fermentation with help from a $5 million investment from the Bill & Melinda Gates Foundation. The company first developed its biotech route to the drug in 2005. The product is also derived from the herb sweet

ONCOLOGY

▸ Juno boosts cellular therapy partnerships

Juno Therapeutics will collect $50 million now that Celgene has exercised an option to develop its cellular therapies targeting CD19 outside of North America and China. Juno’s CD19 portfolio includes three drug candi-dates; one, JCAR015, is in Phase II studies to treat acute lymphoblastic leukemia. Last year, Celgene paid $1 billion for the rights to opt in to Juno’s cellular therapies. Separate-ly, Juno and WuXi AppTec have started JW Biotechnology in China to pair Juno’s cellu-lar therapy technology with WuXi’s R&D and manufacturing expertise. —LISA JARVIS

ONCOLOGY

▸ Sean Parker launches cancer institute

The foundation started by tech billionaire Sean Parker is putting up $250 million to create the Parker Institute for Cancer Immunotherapy, which will support 300 researchers across six academic cancer centers. The institute plans to develop cell-based therapies, expand the number of patients who benefit from checkpoint ther-apies, and find tumor antigen targets that could lead to cancer vaccines. Any intellec-tual property it generates will be licensed

BIOBASED CHEMICALS

▸ Paper company makes lignin from pulp

In a Canadian first, forest products compa-ny West Fraser has begun producing lignin in a $24 million facility at its pulp mill in Hinton, Alberta. The company will use the papermaking by-product to make a natural adhesive for its engineering wood prod-ucts, where it will substitute for synthetic resins. The company says lignin can also be used to make renewable chemicals, ther-moplastic composites, and packaging. —MELODY BOMGARDNER

An Amyris researcher examines genetically modified microbes under a microscope.

AM

YR

IS

wormwood, but supplies are subject to shortages. —MELODY BOMGARDNER

or spun off into a company, with proceeds being divided between the institute and the six academic sites. —LISA JARVIS

DEET

N

O

16 C&EN | CEN.ACS.ORG | APRIL 18, 2016

AS

SO

CIA

TE

D P

RE

SS

The water chemistry is improving in Flint, Mich., but the city’s water is still breaking the federal rule for lead levels, according to tests led by Marc A. Edwards’s team at Virginia Tech.

Edwards and his team helped expose the water crisis in Flint last year. They un-veiled new results at a press conference on April 12 from samples collected by 174 Flint residents last month. These samples came from homes that the team also analyzed in its 2015 study.

EPA and Michigan officials have tak-en steps to improve Flint’s water qual-ity since Edwards and his colleagues showed that the city’s water was corroding pipes and leaching lead into the water. For example, Flint’s pipes once again carry treated water from Detroit, rather than treated Flint River water. The Detroit water is less corro-sive than the river’s, in part, because it has lower chloride levels and contains

an orthophosphate corrosion inhibitor.Yet 15% of the samples collected last

month had lead concentrations higher than 15 ppb, the EPA’s action level, with one sam-ple exceeding 2,000-ppb lead, according to the team’s tests. Compliance with EPA’s Lead & Copper Rule requires that no more than 10% of households in an area can ex-ceed the 15-ppb threshold. “Our hopes were

that the lead levels would have dropped more than they did,” Edwards said.

Flint’s residents are using little water, on the order of 20–45% of typical water use around the U.S., Edwards said. This low usage delays the delivery of protective orthophosphate to plumbing and slows the removal of lead that leached into the sys-tem, he added.

Pushing more water through the pipes would enhance the delivery of phosphate, says Susan Masten, an environmental engi-

neer at Michigan State University who was not involved with the study. “But whether the lead levels are related to low water usage is unproven,” she says. “We simply don’t know how effective increasing water consumption will be.”

Still, the recommended course of ac-tion is to flow more water through the pipes to enhance the delivery of ortho-phosphate, as well as the removal of re-sidual lead, Edwards said. “The system is definitely on its path to recovery, but we’ve got to get more water flowing.” —MATT DAVENPORT

Despite improvements, new data still exceed federal action level

Lead levels remain high in Flint’s waterWATER

Policy Concentrates

A nine-year-old took his enthusiasm for 3-D printing all the way to the White House, where he met President Barack Obama last week. Jacob Leggette of Baltimore, Md., who creates toys using a 3-D printer, watches as Obama blows a soap bubble using a bubble wand that Leggette 3-D printed. The event, started by the Obama Administration in 2010, marks the President’s sixth and final White House Science Fair. —JESSICA MORRISON

Obama hosts his last Science FairK–12 EDUCATION

3.6 million

Number of people in the U.S. served by drinking water systems that exceeded the federal lead standard at least once between Jan. 1, 2013, and Sept. 30, 2015, according to an analysis of Environmental Protection Agency data by the Associated Press.

BY THE NUMBERS

Lead still lingersWater samples collected in 2015 and 2016 from household taps in Flint, Mich., af er at least six hours of no use show that lead levels remain high.

2015 2016

Samples exceeding lead action level 19% 15%

Samples with no lead detected 10% 38%

90th percentile lead levela 29 ppb 23 ppb

Median lead level 4.4 ppb 1.8 ppb

Maximum lead level observed 158 ppb 2,253 ppb

a 90% of samples were at or below this lead concentration Source: flintwaterstudy.org/Virginia Tech

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 17

CONSUMER PRODUCTS

▸ Preservative in leave-on cosmetics banned in the EU

Methylisothiazolinone will be banned in body lotions, deodorants, and other leave-on cosmetics sold in the European Union later this year. The European Commission’s Standing Committee on Cosmetic Prod-ucts voted in favor of the preservative’s ban earlier this month. The chemical, which is used in many personal care products, has

been associated with allergic skin reactions and skin sensitiza-tion. Last year, the commission

banned mixtures of methylchloroisothi-azolinone and methylisothiazolinone in leave-on cosmetic products. Consumer groups are welcoming the ban on methyli-sothiazolinone, but they are urging the commission to also take action to restrict the preservative in rinse-off personal care products such as shampoo. Earlier this month, the commission proposed to limit the amount of methylisothiazolinone in rinse-off personal care products to 15 ppm. The commission is accepting comments on the proposed limit until July 1. The stand-ing committee is expected to vote on the proposal for rinse-off products early next year. —BRITT ERICKSON

PERSISTENT POLLUTANTS

▸ India bans manufacture, import of PCBs

India has banned the manufacture and import of polychlorinated biphenyls (PCBs), as well as the import of equipment containing these carcinogenic, synthetic organic chemicals. Under the order, an-nounced on April 6 by India’s Ministry of Environment, Forests & Climate Change, “the use of PCBs in any form shall be com-pletely prohibited” by the end of 2025. The decision is in line with the Stockholm Con-vention on Persistent Organic Pollutants that India signed in May 2002 and ratified in January 2006. Import, export, or trade of PCB-contaminated equipment will be regulated as hazardous waste under the new directive. The use of PCB-contain-ing equipment shall be permitted for the equipment’s certified lifetime or until Dec. 31, 2025, whichever is earlier, provided the equipment is maintained properly without the possibility of leakage or release of PCBs into the environment. —K. V. VENKATASU-BRAMANIAN, special to C&EN

AGRICULTURE

Farmers plant fewer genetically modified cropsFor the first time since 1996, farmers worldwide planted fewer acres of genetically modified crops in 2015, down 1% from 2014 to 444.0 million acres. The decline is partly attributable to increased regulation, ac-cording to the International Service for the Acquisition of Agri-Biotech Applications, the industry group that reported the results. —ANDREA WIDENER

INDUSTRIAL SAFETY

▸ Reforms haven’t made offshore drilling safer, report finds

Regulatory changes enacted after the 2010 Gulf of Mexico oil rig disaster are inadequate to protect workers, reduce risk, and prevent similar future offshore accidents, says a new report by the Chemical Safety Board. A “culture of minimal regulatory compliance continues to exist in the Gulf and risk reduc-tion continues to prove elusive,” the report says. The Deepwater Horizon accident killed 11 workers and caused the biggest oil spill in the history of offshore drilling. CSB investigators found that the responsible companies had corporate risk management policies more rigorous than what is required by regulation, but they did not implement them. New regulatory changes still fail to U

.S.

CO

AS

T G

UA

RD

place the onus on industry to proactively re-duce risk or empower regulators to prevent another disaster, the report says. A “cultural shift” in oversight and new tools to evaluate and monitor safety performance, including “meaningful worker participation,” are needed, the report says. The report still needs to be approved by the full CSB, which will vote on it later this month. It marks the third and final CSB report on the accident. —JEFF JOHNSON, special to C&EN

Regulatory oversight is inadequate to prevent another disaster like the 2010 Gulf of Mexico oil rig explosion, a CSB report warns.

Source: International Service for the Acquisition of Agri-Biotech Applications

175.2

109.2

60.5

28.7

27.2

9.1

8.9

7.2

5.7

3.5

U.S.

Brazil

Argentina

India

Canada

China

Paraguay

Pakistan

South Africa

Uruguay

Area, million acres

Top 10 producers of genetically modified crops in 2015

Methylisothiazolinone

CH3

NS

O

18 C&EN | CEN.ACS.ORG | APRIL 18, 1016

Chemical makers surveyed by C&EN say they funded R&D in 2015 at about the same rate as they did the year before. But they cut back on capital spending and plan to continue the

pullback in 2016. The lackluster global economy crimped spending

on research and new plants, but it wasn’t just that. Activist investors, with their bottom-line orientation, influenced corporate executives to focus on efficiency by reining in costs, merging with competitors, spinning off businesses—or all of the above.

Under activist pressure, Ashland, for instance, sold its water treatment business in 2014 . Air Products & Chemicals will soon spin off its chemical operations. An activist agenda also motivated the industry’s big-gest-ever merger: Dow Chemical and DuPont will com-bine later this year , only to separate into three separate firms in 2017.

DuPont’s chief science and technology officer, Douglas Muzyka, tells C&EN that the corporate changes are accompanied by cutbacks at the firm in-tended to rightsize and breathe new life into its R&D operation as it readies for what’s to come. DuPont’s R&D spending fell 8.2% in 2015 to $1.9 billion. For 2016, the firm is again ratcheting back outlays , this

“Yes, we are making cuts. But we haven’t undermined our long-term commitments to research.”

—Douglas Muzyka, chief science and technology officer,

DuPont

BUSINESS

Future spending stalls this year Spin-offs and consolidation take a toll on big chemical firms’ outlays for research and construction

MARC S. REISCH , C&EN NEW YORK CITY

time by 13% to between $1.6 billion and $1.7 billion.

A C&EN survey of 18 U.S. and European chemical firms finds they collectively kept 2015 R&D spending at essentially the same level as in 2014. In addition to DuPont, only two other companies were willing to share their 2016 R&D plans. BASF said it will keep spending flat at about $2.2 billion, and 3M said it plans to increase it by 2% to about $1.8 billion.

In recent years, f ewer and fewer com-panies have been willing to provide R&D projections . Martin Grueber, a research leader at Battelle Memorial Institute who coauthors a periodic R&D funding forecast, suggested to C&EN last year that this is because investors don’t have a good grasp of how hard R&D is. Companies have decid-ed, Grueber said, that “if you can get away without saying something, it raises fewer questions.”

As a result of this reticence, C&EN won’t make an R&D spending forecast for 2016. Instead, we look back: In the table accompa-nying this article, we provide spending lev-els through 2015 based on reports in finan-cial documents for the 18 listed companies.

However, the surveyed firms do provide capital spending forecasts for 2016. Collec-tively they plan to cut new plant and equip- B

AS

F

Features

Technician Lucas Montag prepares semiconducting graphene materials at BASF’s Ludwigshafen, Germany, site.

APRIL 18, 1016 | CEN.ACS.ORG | C&EN 19

ment spending by 10.1%. They trimmed spending 2.7% in 2015.

A subgroup of 17 major U.S. and Euro-pean chemical firms, excluding Evonik Industries because 10 years of data are not available, is spending $9.4 billion on R&D in 2015, up a hefty 42% compared to a de-cade ago. After adjusting for inflation, the increase is about 18% over the same period. The share of company sales devoted to R&D generally hovers around 3%, but this year it reached a decade high of 3.4%.

The 17 firms are planning to spend $18.4 billion on capital projects in 2016, up a respectable 44% compared with a 2005. Spending in 2016 will mark the second year of decline following five years of growth be-ginning in 2010 after the Great Recession.

C&EN predicts that capital spending as a percentage of sales for the 17 firms will be 6.5% this year, down from the 10-year peak of 7.5% last year. The estimate assumes col-lective sales for the group will increase 2.5% in 2016. The decade low occurred in 2010 when the group spent just 4.7% of sales on equipment.

When it comes to R&D spending plans, perhaps no company is more emblematic of the times than DuPont. While under attack by the activist investor Nelson Peltz, DuPont spun off its fluorochemicals and titanium dioxide franchises as a new firm known as Chemours.

Without Chemours, DuPont’s R&D bud-get slipped in 2015. The year was a difficult one for what remained of DuPont as the firm’s agricultural business, like those of its competitors, saw sales fall. Partly as a re-sult, R&D as a percent of sales rose to 7.6%, a number out of sync with DuPont’s spend-ing level over the past decade of around 5 to 6%, Muzyka says.

Paring back to an R&D budget in 2016 of about $1.65 billion will take the firm’s spending to roughly the level of 2010. The reduction is part of an overall restructuring program at the firm that includes eliminating 10% of its 54,000 employees and cutting costs by $700 mil-

lion in advance of the merger with Dow. According to C&EN sources, those cuts

included the dismissal in January of more than 200 scientists at DuPont’s Central Research & Development. “Yes, we are making cuts,” Muzyka says. “But we haven’t undermined our long-term commitments to research.”

For DuPont’s agriculture business, that means slowing some commercialization efforts but continuing “to push projects we believe in,” Muzyka says. In the firm’s spe-cialty products business, he adds, a priority is the cellulosic ethanol project recently started up in Iowa and “making sure that it is keyed for success.”

CHANGE R&D SPENDING AS % OF SALES

$ MILLIONS 2010 2011 2012 2013 2014 2015 2013–14 2014–15 2014 2015

3M $1,434 $1,570 $1,634 $1,715 $1,770 $1,763 3.2% -0.4% 5.6% 5.8%

Air Productsa 115 119 126 134 141 139 5.2 -1.4 1.4 1.4

Albemarleb 58 77 79 82 88 103 7.3 17.0 3.6 2.8

Arkemac 155 147 164 166 172 232 3.6 34.9 2.6 2.7

Ashlanda,d 86 89 137 178 114 110 -36.0 -3.5 1.9 2.0

BASF 1,656 1,781 1,937 2,036 2,090 2,167 2.7 3.7 2.5 2.8

Cabota 70 66 73 74 60 58 -18.9 -3.3 1.6 2.0

Celanese 70 96 102 85 86 119 1.2 38.4 1.3 2.1

Clariante 140 183 182 188 221 212 17.7 -4.2 3.5 3.5

Dow Chemical 1,660 1,646 1,708 1,747 1,647 1,598 -5.7 -3.0 2.8 3.3

DuPontf 1,651 1,956 2,067 2,153 2,067 1,898 -4.0 -8.2 6.0 7.6

Eastman Chemicalg 152 158 198 193 227 251 17.6 10.6 2.4 2.6

Evonik Industries 375 405 436 437 458 482 4.8 5.2 3.2 3.2

FMC 101 105 118 118 129 144 9.3 11.6 3.2 4.4

W.R. Grace 60 69 65 65 80 70 23.1 -13.0 2.5 2.3

Huntsman Corp. 151 166 152 140 158 160 12.9 1.3 1.4 1.6

Praxair 79 90 98 98 96 93 -2.0 -3.1 0.8 0.9

Solvayh 139 173 290 333 274 307 -17.7 12.0 2.3 2.2

TOTAL $8,152 $8,896 $9,566 $9,942 $9,879 $9,906 -0.6% 0.3% 3.1% 3.4%

ANNUAL CHANGE 3.1% 9.1% 7.5% 3.9% -0.6% 0.3%

Research investments On average, 18 major chemical fi rms kept spending fl at last year

a Fiscal year ends Sept. 30. b Bought Rockwood in 2015. c Bought Bostik in 2015. d Bought ISP in 2011. e Purchased Süd-Chemie in 2011. f Acquired Danisco in 2011. g Purchased Solutia in 2012. h Bought Rhodia in 2011 and Cytec Industries in 2015. Source: C&EN surveys

$ Billions

200506 07 08 09 10 11 12 13 14 15

5

6

7

8

9

10% of sales

200607 08 09 10 11 12 13 14 15 16

2.0

2.5

3.0

3.5

4.0▪ Current

▪ Constant 2005

Research trends R&D spending slipped in constant dollar terms last year but hit a 10-year peak as a percent of sales

Note: Values are for 17 chemical firms listed in the table below. Excludes Evonik Industries because 10 years of data are not available. Sources: C&EN surveys, White House Office of Management & Budget

20 C&EN | CEN.ACS.ORG | APRIL 18, 1016

The Central R&D operation at DuPont had opened up in recent years through research collaborations with university partners, Muzyka says. Now he’s emphasiz-ing that strategy in-house as well. “We will still have a capable cadre of people” doing research at the firm’s Wilmington, Del., headquarters, Muzyka says, but they will be “interfacing more” with DuPont scientists at other sites.

For instance, scientists who work in Wilmington will link with those in the Tiburon, Calif., labs of Taxon Biosciences, a developer of microbial products for agricul-ture that DuPont acquired last year. Other microbiome efforts will match Wilming-ton-based researchers with colleagues in Denmark and Iowa. Those sites are home, respectively, to labs run by enzyme maker Danisco and seed expert Pioneer, both owned by DuPont.

Muzyka acknowledges that “another reorganization and optimization” is in store when Dow and DuPont combine later this year. For the brief time they function as one, their combined R&D spending will dwarf that of most other chemical firms, even with the $300 million in R&D cuts they plan. And after the DowDuPont R&D organization gets divided among the three future companies, Muzyka expects the re-searchers will help make them places where “science is a driving force.”

Whereas Dow and DuPont are just on their way to separating into more focused businesses, W.R. Grace has already com-pleted such a journey. In February Grace spun out its construction products and packaging business, GCP Applied Technol-ogies, to shareholders, leaving Grace as a stand-alone maker of process catalysts and specialty silicas.

Dow and DuPont have overlapping busi-nesses that must be untangled carefully. But that was not the case for Grace. There, the separation involved very different businesses, so there was little overlap in the R&D organizations, according to Bob Gatte, Grace’s chief technologist. His firm lost some analytical expertise in the split,

he admits, but nothing it couldn’t replace. Grace will spend close to 3% of sales

on R&D in 2016. That number is higher than the 2.3% of sales the combined firm spent before the split, reflecting the opportunities the new Grace sees for itself, Gatte says. Research priorities will be in new catalysts, customer application support, and manufacturing improvements.

No doubt Muzyka and Gatte under-stand the importance of research to their companies’ future success. But they still must convince skeptical investors that R&D funded by the profits of today won’t detract from shareholder returns tomorrow. ◾

$ Billions

200607 08 09 10 11 12 13 14 15 16

10

13

16

19

22

% of sales

200607 08 09 10 11 12 13 14 15 16

4

5

6

7

8

Capital ideas Af er rising steadily for fi ve years, capital spending will slip to 6.5% of sales in 2016

Note: Values are for 17 chemical firms listed in the table above. Excludes Evonik Industries because 10 years of data are not available. Source: C&EN surveys and estimates

a April 2015 estimates. b Actual 2015 financial report. c Budget for 2016. d Actual 2014 to actual 2015. e Actual 2015–16 budget. f Fiscal year ends Sept. 30. g Bought Rockwood in 2015. h Bought Bostik in 2015. i Bought ISP in 2011. j Purchased Süd-Chemie in 2011. k Acquired Danisco in 2011. l Purchased Solutia in 2012. m Spun out GCP Applied Technologies in 2016. n Bought Rhodia in 2011 and Cytec Industries in 2015. Source: C&EN surveys

CHANGE

$ MILLIONS 2010 2011 2012 2013 2014 Planned 2015a Actual 2015b Planned 2016c 2014–15d 2015–16e

3M $1,091 $1,379 $1,484 $1,665 $1,493 $1,600 $1,461 $1,400 -2.1% -4.2%

Air Productsf 1,298 1,352 1,521 1,524 1,682 1,725 1,615 1,550 -4.0 -4.0

Albemarleg 76 191 281 155 111 235 228 235 105.4 3.1

Arkemah 350 471 486 534 522 499 478 522 -8.3 9.0

Ashlandf,i 206 201 298 314 248 288 265 330 6.9 24.5

BASF 2,827 3,784 4,549 4,882 5,659 4,438 5,770 4,660 2.0 -19.2

Cabotf 108 230 281 264 171 225 141 150 -17.5 6.4

Celanese 201 349 361 370 678 388 520 275 -23.3 -47.1

Clariantj 233 385 323 303 322 317 389 338 20.6 -13.0

Dow Chemical 2,130 2,687 2,614 2,302 3,572 3,900 3,703 3,800 3.7 2.6

DuPontk 1,508 1,843 1,793 1,882 2,020 1,800 1,629 1,125 -19.4 -30.9

Eastman Chemicall 243 457 465 483 593 712 652 652 9.9 0.0

Evonik Industries 723 921 1,065 1,202 1,246 1,221 973 973 -21.9 0.0

FMC 142 190 207 272 225 163 109 109 -51.6 0.0

W.R. Gracem 113 142 139 156 170 178 155 200 -8.9 29.2

Huntsman Corp. 236 327 412 471 601 625 663 450 10.3 -32.1

Praxair 1,388 1,797 2,180 2,020 1,689 1,700 1,541 1,500 -8.8 -2.7

Solvayn 317 668 871 899 1,096 1,145 1,212 1,054 10.5 -13.0

TOTAL $13,190 $17,374 $19,331 $19,698 $22,098 $21,503 $19,323 -2.7% -10.1%

ANNUAL CHANGE 13.0% 31.7% 11.3% 1.9% 12.2% -2.7% -10.1%

Capital outlays Spending to sink more than 10% for C&EN’s survey group as both BASF and DuPont cut back

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 21

Lee Blaney tells people he has the best-smelling lab on the campus of the University of Maryland, Baltimore County (UMBC).

He’s joking. The environmental engineer and his team operate reactors bubbling with slurries of chicken manure that give off a stinky ammonia odor.

“Once you get used to it, it’s really not that bad,” Blaney says. “But probably only people who deal with a lot of crap get used to it.”

Blaney and his students willingly live with this stench because they see a resource trapped in the smelly waste.

At last month’s American Chemical Society national meeting in San Diego, Blaney’s graduate student Utsav Shashvatt reported on the group’s process to extract phosphorus from chicken litter, the dry, dirtlike mixture of manure and other debris farmers scrape from the bottom of their chicken houses.

By pulling phosphorus out of the ma-nure, the researchers hope to provide a sustainable source for the agriculturally vital nutrient. The technology is one of sev-eral approaches environmental engineers are working on to help Maryland chicken farmers turn their manure into valuable products while also responding to regula-tions designed to improve the water quality in the nearby Chesapeake Bay.

For decades, the Chesapeake has suf-fered from low-oxygen, or hypoxic, dead zones , which are uninhabitable for crabs, fish, and other native species. These dead zones are largely caused by nutrient pol-lution—nitrogen and phosphorus—that washes off the land and into waterways that feed into the Chesapeake, says Bill Ball , the executive director of the Chesapeake Re-search Consortium, which coordinates and communicates research on the bay. A large

portion of this pollution comes from agri-cultural lands. Just as these nutrients help crops grow on farms, the compounds fuel the growth of algal blooms in the bay. When these algae die, bacteria consume them, using up the water’s dissolved oxygen and creating the dead zones.

Chicken manure contributes to the bay’s nutrient pollution. Farms on the Delmarva Peninsula—which forms the bay’s Eastern Shore and consists of most of Delaware and parts of Maryland and Virginia—raise more than half a billion chickens per year and pro-duce millions of tons of manure, Blaney says. “The easiest thing to do—and what has been historically successful—is to use that litter as fertilizer,” he says. In fact, many farmers see the manure as a valuable resource that they can apply to their own fields or sell to others.

But when chicken litter is used as fertiliz-er, it’s easy to add more phosphorus to soils than crops need, Ball says. Compared with other manures, such as those from cows and pigs, poultry litter contains a relatively high ratio of phosphorus to nitrogen. “Because the manure is cheap and farmers have to get rid of it, they often end up overapplying phosphorus,” Ball says. When oversaturated with phosphorus, soils can start to leach the nutrient into nearby waterways.

Last year, Maryland instituted regulations that could significantly restrict farmers’ use of chicken litter. The regulations, called the Phosphorus Management Tool, are part of the state’s plans to curtail nutrient pollution flowing into the Chesapeake. Maryland, along with the District of Columbia and the other five states—New York, Pennsylvania, West Virginia, Delaware, and Virginia—with waterways that drain into the bay, must de-velop plans to meet nitrogen and phospho-rus limits set by the Environmental Protec-tion Agency under the Clean Water Act.

When the new regulations are fully imple-mented in 2022, the amount of phosphorus farmers can apply to their fields will be re-stricted, in part, by how much of the element is already in the soil.

This could create manure problems for farmers such as Lee Richardson. On his farm in Wicomico County, Md., Richardson raises chickens—about 175,000 broilers at a time in six houses—and grows corn and soybeans on 2,000 acres of land.

More than half of the farms in the lower part of Maryland’s Eastern Shore, where Wicomico is located, have soil phosphorus levels that would trigger the new regula-tions. And about 10% are already prohibited from applying phosphorus because of ex-cessively high soil levels.

Based on the new regulations and his farm’s soil levels, Richardson says by E

DW

IN R

EM

SB

ER

G/V

WP

ICS

/NE

WS

CO

M

ACS MEETING NEWS

Much ado about chicken poo Environmental engineers look for sustainable ways to deal with manure in Maryland

MICHAEL TORRICE , C&EN WEST COAST

Moving manure in a Maryland chicken house.

“What we really wanted to do was find how to best utilize the full chemistry of the raw poultry litter.”

— Lee Blaney , professor of engineering, University of Maryland, Baltimore County

22 C&EN | CEN.ACS.ORG | APRIL 18, 2016

2018 he might not be able to add more phosphorus to his fields.

So farmers like him will have to find a way to get rid of their chicken litter. One solu-tion is to truck it out of the Eastern Shore to farmers with land that can still take phos-phorus. Although the state runs a program that helps with manure transportation costs, Richardson says it can get expensive.

Blaney thinks his team’s solution could be another option for farmers. Nitrogen and phosphorus make up just a tiny frac-tion of the mass of chicken litter. So most of what is shipped by farmers—and what contributes most to transportation costs—lacks the nutrients that farmers want.

By extracting the phosphorus from the manure, “we’re not pulling out much of the

actual mass of the poultry litter—no more than 5%,” Blaney says. “But we’re pulling out the good stuff.” Those nutrients would be valuable for other farmers needing phos-phorus for their crops, and would be in an easier and less expensive form to ship.

The extraction process takes place in two separate reactors and starts with a slurry of the poultry litter. In the first reactor, the engineers bring the slurry’s pH down to about 5, which releases am-monium and phosphates from the manure and into the water. The liquid is separated from the remaining solid and pumped into the second reactor. There, the team increases the liquid’s pH to about 9, which

causes the end product, phosphorus-rich minerals, to precipitate out.

In their lab-scale tests, the engineers can recover between 80 and 90% of the phos-phorus in a litter sample. Mostly, the team produces an ammonium phosphate min-eral called struvite (MgNH 4 PO 4 •6H 2 O), which can serve as a slow-release fertilizer for crops. But they also precipitate out a calcium phosphate mineral (CaHPO 4 ) that could be used as a nutrient supplement in animal feeds.

And the solid leftover in the first reactor isn’t just waste. It is still rich in organic matter, making it useful as a fertilizer that farmers could apply to fields without worry-ing about adding to their phosphorus levels. Blaney says the material could also be used

in anaerobic digestion, a process that uses microbes to break down organic matter to produce biogas, a mixture of methane and carbon dioxide that can be burned as fuel.

Other phosphorus extraction methods already exist, including ones to pull out the nutrient from wastes such as biosolids left-over after wastewater treatment. But, Blaney says, those processes are often energy-inten-sive and require the addition of magnesium and ammonium to produce minerals.

To make this process sustainable, Blaney and his team want to minimize the amount of water and chemicals required. When the engineers analyzed the composition of chicken litter, they realized that it had all the

elements they needed to form struvite. So the only additions they make are in the steps to acidify the slurry and precipitate the min-erals. “What we really wanted to do was to find how to best utilize the full chemistry of the raw poultry litter,” Blaney says.

For the acidification step, the team de-cided to skip strong acids, which Blaney says would add to the cost of the process. Instead, the researchers bubble carbon dioxide into the manure slurry. To increase the pH in the second reactor, the engineers add sodium hydroxide and bubble in air to push out any residual CO 2 .

To reduce the water they use, the re-searchers pump out the liquid remaining in the second reactor at the end of the process and use it to form the slurry for the next manure batch. They can recycle the liquid through 10 cycles and still recover greater than 80% of the litter’s phosphorus.

Stephanie A. Lansing , an ecological engi-neer at the University of Maryland, College Park, says the extraction method is one way to increase the sustainability of chicken farming. Farmers import feed onto the Eastern Shore for their chickens, she says. “A portion of that comes out in the manure. But those nutrients stay on the shore and don’t necessarily go back to where the feed is grown.” Extracting the phosphorus and shipping it back to the feed growers could help close that loop.

Lansing is also working on other uses for chicken litter. She’s developing two tech-nologies that turn the manure into energy. The first uses anaerobic digestion to pro-duce biogas, and the other gasifies the ma-nure into syngas, a fuel consisting mostly of hydrogen and carbon monoxide. Her group has demonstrated the technologies at mul-tiple scales—from lab to farm scales.

Blaney is working with Triea Technol-ogies, a small Maryland agricultural tech-nology company, to translate his team’s extraction process into an on-farm system. He hopes to have such a system running on Richardson’s farm in Wicomico within the next year.

Richardson sees the extraction technolo-gy as a win-win situation for farmers. “If they can make it economical and I can get the by-products back—the organics and minor elements—it solves two problems: Me not losing my manure, and making the state hap-py with no phosphorus going on the field.”

For Ball, whether it’s converting chicken litter into an easy-to-transport fertilizer or a gaseous fuel to be burned, finding other uses for the manure will certainly help the water quality in the Chesapeake watershed. “A good solution,” he says, “would be one that is economically beneficial and is better than applying it to the land.” ◾

Pulling out the good stuff To extract phosphorus from chicken litter, engineers add a slurry of the manure to a reactor and bubble in CO 2 to drop the pH to about 5. This releases ammonium and phosphates into the water, which is then pumped into a second reactor. There, the en-gineers add sodium hydroxide and air to increase the pH to 9 to precipitate out struvite and other phosphate minerals. The remaining liquid can then be recycled into the fi rst reactor to make the slurry for the next batch of manure.

AD

AP

TE

D F

RO

M L

EE

BL

AN

EY

(S

CH

EM

AT

IC);

LE

E B

LA

NE

Y (

PH

OT

OS

)

Raw poultry litter

Mixers

Nitrogen- and phosphorus-rich liquid

Recycled liquidsReactor 1 Reactor 2

pH~5.0 pH~9.0

Low-nutrient litter Struvite

Solids Solids

CO2 NaOH/air

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 23

Assessments of drug raw materials are conducted at Cadila Pharmaceuticals, which FDA cited for poor safeguards against data tampering.

When visiting drug plants outside their home country, U.S. Food & Drug Ad-ministration inspectors typically have just a few days to determine whether

the facilities comply with manufacturing standards. In the case of Pan Drugs, inspected in July 2014, it was an easy task.

“ Our investigator observed holes in the walls and roof which allowed pigeons access near production equipment in multiple manufacturing areas,” read the warning letter that FDA sent to the firm last September to explain why products made at the plant, in Vadodara, India, would be banned from the U.S.

Dr. Reddy’s Laboratories, one of the biggest names in India’s drug industry, similarly failed spectacularly. Several days into a late-2014 inspection, FDA officials discovered a lab, not previously disclosed by the firm, that had analyzed active pharmaceutical ingredients exported to the U.S. Inspectors found that the secret lab kept retesting batches that had failed quality tests until positive results were obtained.

More often, though, the problems that FDA uncov-ers are less obvious than they were at Pan Drugs and Dr. C

AD

ILA

PH

AR

MA

CE

UT

ICA

LS

“Until May 2013, regulators in the U.S. and Europe took what was presented to them by companies based in India at face value.”

— Dinesh S. Thakur , executive chairman, Medassure

Global Compliance

DRUG SAFETY

Indian drug firms struggle with quality issues More and more companies are challenged by FDA’s scrutiny of manufacturing records

JEAN-FRANÇOIS TREMBLAY , C&EN HONG KONG

Reddy’s. In recent years, dozens of plants in India have been cited for “data integrity” is-sues in warning letters sent by FDA officials or their regulatory counterparts in other countries. Harder to fix than holes in a wall, data issues are likely to plague Indian firms for years to come and could threaten their role as leading U.S. suppliers of generic drugs.

“ ‘Data documentation issues’ is not the case of a sloppy secretary failing to file test reports alphabetically but a serious issue, one which has an impact on the lives of human beings,” wrote Dinesh S. Thakur last month in the Indian magazine Business Today. “If a batch fails a test, a manufacturer is required to withdraw the consignment from the market—in most cases this would result in a loss to the manufacturer. The simpler, unethical, and illegal way around this problem is to delete the failed test re-cords and replace them with manipulated test records that demonstrate that the batch passed quality assurance tests.”

Based in Tampa, Fla., Thakur is head of Medassure Global Compliance, a consulting firm advising companies on their phar-maceutical supply chains. Thakur was the whistle-blower who alerted FDA in 2007 to

24 C&EN | CEN.ACS.ORG | APRIL 18, 2016

systematic manipulation of manufactur-ing records at Ranbaxy Laboratories. The company was fined $500 million in 2013 for its transgressions. Thakur was expected to receive about 10% of it.

It was the fraud committed by Ranbaxy, which is now part of Sun Pharmaceutical Industries, that led FDA to more broadly question the validity of data submitted by drug manufacturers, Thakur tells C&EN. “Until May 2013, regulators in the U.S. and Europe took what was presented to them by companies based in India at face value,” he says. “Ranbaxy changed that.”

Although FDA’s new focus on data in-

tegrity is worldwide, it has proven most damaging to India. In the past five years, of the 29 warning letters citing data integrity issues that FDA sent to companies around the world, 18 related to facilities in India (C&EN, April 4, pg. 15). A common problem uncovered in its inspections is failure to pre-vent unauthorized access to test data, which leaves inspectors unsure as to whether the data companies are presenting amount to a complete and accurate picture of their man-ufacturing performance.

Thakur reckons that 44 Indian drug plants are currently banned from exporting to the U.S., a number that he says is evidence of a systematic problem with the country’s drug industry.

According to a recent report by the In-dian Pharmaceutical Alliance, an industry group whose members include India’s most prominent drug firms, a total of 379 plants have at some point been authorized by FDA to export pharmaceuticals to the

U.S. Fully a third of the drugs sold in the U.S. in 2014 were manufactured in India, the report says.

The focus on data integrity at FDA, and at its counterparts in Europe and Japan, has kept Indian firms on alert for some time. Yusuf K. Hamied, the chairman of Cipla, which has yet to receive an FDA warning letter, told C&EN in December 2013 that whenever a competitor receives such a let-ter, Cipla employees review it to make sure that the firm’s facilities don’t have a similar problem.

At the time of the interview, a manufac-turing quality consultant who previously

worked at the World Health Organization was auditing one of Cipla’s main active ingredient plants to make sure its systems were in order.

That kind of self-auditing is costly, but failure to meet FDA requirements is likely dearer. In 2013, for example, the agency issued two warning letters to Wockhardt, banning two of the company’s plants from exporting to the U.S.

Until then, Wockhardt’s sales in the U.S. had been steadily expanding, to the point that they accounted for more than 40% of total sales. With two of its plants banned from exporting to the U.S., Wockhardt’s sales dropped by 14% in the fiscal year that ended March 31, 2014. Profits fell by nearly half.

Given that the financial penalty for non-compliance can be so high, it is perplexing that many Indian drug exporters have not taken the steps required to ensure that their manufacturing standards meet those of

Trail of negligence FDA warning letters issued to Indian drug firms cite a litany of problems.

Note: List is not comprehensive. Source: FDA

Over 14,000 unique reagentsfor medicinal chemistryand library synthesis

Available overnight fromSan diego stock via our

e-commerce portalHit2Lead.com

San Diego, CA 92121

Tel: +1-858-451-7400, Option #4support@chembridge.com

www.hit2lead.com

CHEMBRIDGE:

A MAJOR FORCEIN BUILDING

BLOCKS

BORONIC ACIDS

CARBOXYLIC ACIDS

PRIMARY AND SECONDARY AMINES

ARYL BROMIDES

N

N

NH2

F F

NH2

HCl

NN

NH2

HCl

CH3

2

HN

HCl

CH3

CH3

CH3

NHHCl

HO

HN

O

NH

HCl

CH3

S

O

O

N Br

CH3

NN

HN

Br

CH3

N

NS

Br

O

O

Br

N

B

O

OH

OH

H3C

B

O

O

CH3

H3C

H3C

H3

C

OH

B

O

O

OH

F

CH3

CH3

CH3

H3C

H3C

B

O

O

N

CH3

CH3

CH3

CH3

N

HNO

OH

HClCH3

NO

OH

O

OH

HClNH2

O O

HO

H3C

CH3

Na

COMPANY DATE OF WARNING MAJOR OBSERVATIONS

Emcure Pharmaceuticals March 2016 Failure to prevent contamination

Ipca Laboratories January 2016 Retesting of samples without reason, data manipulation, lack of

oversight

Cadila Healthcare December 2015 Failure to investigate failed batches, poor safeguards against data tampering, discovery of notebooks in trash

Sun Pharma December 2015 Failure to investigate failed batches, inadequate facility maintenance, inconsistent investigation of test anomalies

Dr. Reddy’s (three plants) November 2015 Incomplete data, batch retesting, poor safeguards against data tampering, operating an undisclosed quality-control lab

Sandoz (two plants) November 2015 Undocumented manufacturing steps, inadequate staff training, failure to investigate failed batches

Pan Drugs September 2015 Shoddy manufacturing facilities, incomplete data

Mylan August 2015 Failure to prevent microbial contamination, poor environmental

monitoring, poor safeguards against data tampering

Mahendra Chemicals July 2015 Destruction of data, incomplete data entry, poor safeguards against data tampering, inadequate employee training

Cadila Pharma ceuticals February 2015 Failure to implement controls after discovering contaminated batches, poor safeguards against data tampering

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 25

Western regulators. But thoroughly fixing the issues could harm the business models of many of them, claims Peter Saxon , pres-ident of Saxon I nternational Associates, a New Jersey-based consulting firm that has advised dozens of Indian and Chinese drug companies on meeting U.S. drug manufac-turing regulations.

“India has always been admired for get-ting products to market fast,” Saxon says. When a drug goes off patent, the first com-pany to come up with a generic version is of-ten an Indian firm. But in rushing, he claims, companies risk going to market with manu-facturing processes that do not consistently produce quality drugs.

Quality control managers at these firms end up with the job of falsifying data to cover up their poorly designed manufacturing pro-cesses, Saxon says.

According to Thakur, the Ranbaxy whis-tle-blower, such data falsification comes easily to Indian firms because Indian regu-lators are much less demanding than West-ern ones. “Indian pharma companies have thrived in a lax and corrupt regulatory envi-ronment for over 30 years now and are not going to change their ways overnight,” he says. Regulators in India do not even investi-gate companies that have been banned from Western countries, Thakur points out.

The West shares some of the blame, ac-cording to drug safety experts. In the U.S., the focus has long been more on drug cost containment than on positive patient out-comes, Thakur says.

One result is that the quality regulation of generics—which account for almost 90% of the drugs sold in the U.S.—is more lax than that of patented drugs, Saxon notes.

In view of the prevalence of quality prob-lems at drugs plants in India and elsewhere overseas, consumers should know where their drugs—and the active ingredients they contain—are made, argues Helena Champion, principal consultant at Drug Quality Assurance, a Boston-based drug manufacturing quality and regulatory com-pliance firm.

“Consumers can read on the label where a clothing item is made, but not where a drug is made,” she says. “Companies can market under a known U.S. or European name and address, even though the product may actu-ally be made by another company in a coun-try where fraud prevails.”

Although it will likely take years for Indian drug manufacturers to solve their data integ-rity issues, a consensus is emerging within India that the country’s pharmaceutical industry needs to change its ways.

Assocham, a federation of Indian cham-bers of commerce, urged the Indian govern-ment in December to tighten its regulation

of the drug industry to force companies to raise their standards and compete on quality. Meanwhile, the Indian Pharma-ceutical Alliance has set up a quality forum, one of the main thrusts of which will be to help its members establish robust data and documentation systems. Several alliance members have received warning letters from FDA.

Despite the Indian drug industry’s prob-lems, the credit rating agency ICRA is opti-mistic about prospects for Indian firms in the U.S. market. In a report last month, ICRA

noted that growth at several leading compa-nies had been curtailed by regulatory issues. But on the whole, it expects the industry to continue launching generic drugs in the U.S. soon after their original versions lose patent protection.

Thakur, the consultant, isn’t so sanguine. Regulators, patients, and buyers in the U.S. are catching on to India’s quality shortcom-ings, he says. And as medical evidence of the impact of substandard pharmaceuticals grows, he expects an American backlash against Indian-manufactured drugs. ◾

5 WAYS TO TRANSFORM

YOUR LABORATORY

abbottinformatics.com

STARLIMS solution provides the flexibility and configuration you need to take on the challenges of today and seize the opportunities of tomorrow.

Information is your lab’s greatest asset. Put it to work with a powerful LIMS

that guarantees data integrity, drives innovation and growth for lab excellence.

AUSTRALIA

Tel: +61 3 9670 0678

GERMANY

Tel: +49 2302 915 244

FRANCE

+33 1 61 37 02 00

LATIN AMERICA

Tel: +1 954 964 8663ASIA PACIFIC

Tel: +852 2793 0699

UNITED KINGDOM

Tel: +44 161 711 0340NETHERLANDS

Tel: +31 72 511 8100

CANADA

Tel: +1 888 455 5467SPAIN

Tel: +34 91 663 67 64

USA

Tel: +1 954 964 8663

4000 Hollywood Blvd, Suite 333 South, Hollywood, FL 33021-6755 USA

AISales@abbott.com

26 C&EN | CEN.ACS.ORG | APRIL 18, 2016

“A rules-based approach to chemical safety education and information is inadequate,” said Ralph Stuart during a symposium at last month’s American Chemical Society national meeting in San Diego.

Stuart, the environmental safety man-ager at Keene State College, recommends something better. Educators should focus on teaching their students hazard and risk assessment skills, Stuart and others believe. This view is bolstered by guidelines issued last year by ACS for two-year college and bachelor’s degree chemistry programs: “Classroom and laboratory discussions need to stress safe practices and should ac-tively engage students in the evaluation and assessment of safety risks associated with laboratory experiences,” say the bachelor’s degree guidelines.

Educators and safety experts shared their approaches and tools for incorporat-ing safety assessments into educational lab curricula at the meeting in San Diego during a Division of Chemical Health & Safety symposium organized by Stuart and Samuella B. Sigmann , a senior lecturer at Appalachian State University.

“We’ve always been concerned about safety in the laboratory for our academic courses, but that’s translated into a few minutes of cautionary comment when giv-ing a prelab lecture. We need to do a better job,” said Lawrence Tirri , a professor of chemistry and biochemistry at the Univer-sity of Nevada, Las Vegas, when introduc-ing his department’s plans.

First, UNLV chemistry and biochemistry first-year graduate teaching assistants, who teach all of the school’s general and organic chemistry labs and assist with upper-level labs, will get more intensive training be-fore classes start in the fall. Because the incoming graduate students have various backgrounds, Tirri wants to use the training to ensure they all meet a basic level of safety awareness and practice. “We’ll talk about chemical hygiene and safety culture con-cepts and go through the tools available for hazard identification and assessing risks,” Tirri said. “We want to make sure they un-derstand what our department expects of them when they go into the labs and what they should convey to their students.”

Then, for the undergraduates taking lab courses, Tirri aims to start including the concepts of hazard identification and risk assessment in the curriculum. Topics will include consideration of the hazards of dif-ferent quantities or concentrations of var-ious materials and safe handling practices. Students will learn basic concepts in general chemistry and engage more deeply as they move to upper-level courses. Lab quizzes and exams will include safety-related ques-tions. In their senior year, students will have to write a full hazard analysis report.

“We’re just starting this journey,” Tirri said. “We’re hoping that it’s going to help students develop their thinking and be more aware of what’s going on around them, not just in the laboratory but in their everyday lives.”

At Appalachian State, deeper engagement with safety occurs at the junior and senior undergraduate level, Sigmann told C&EN. At the junior level, students must take an introductory course on research that covers information literacy, ethics, grant writing, and safety. Sigmann teaches the safety com-ponent, during which she covers types of hazards, components of risk, and where to find safety information. She also goes over how to do a hazard analysis, using changing a lightbulb as an example: As a class exercise, she breaks down the task into steps and goes through the hazards, risk level, and safety controls for each step.

Then the students complete their own hazard analysis for a laboratory procedure.

“The purpose is not to make students responsible for everyone else’s safety behavior but to give the class a sense that we’re all accountable for safety.”

— P. J. Alaimo , professor of chemistry , Seattle University

ACS MEETING NEWS

Teaching hazard assessment Educators move beyond lab safety rules to teach students new skills

JYLLIAN KEMSLEY , C&EN WEST COAST

“The hardest thing for them to wrap their heads around is dividing a process into steps and determining the risk for each step,” she said. “They tend to want to combine or skip steps, such as pouring 30 mL of nitric acid into a beaker, skipping taking that 2.5-L bot-tle out of the cabinet and transporting it. But transporting the bottle is one of the highest hazard steps—if you drop it and it breaks, it’s likely a hazmat situation.”

Students doing research projects in their senior year must also do a hazard analysis as part of their research proposal. “Students are very receptive,” Sigmann said about the hazard assessment assignments. “They stop in for help and say, ‘I’ve never thought about this before.’ ” The skills her students acquire by doing these assessments stay with them as they transition into internships at govern-ment labs or jobs elsewhere, Sigmann said.

Instructors at some schools are incorpo-rating more intensive hazard assessment into their labs at the general and organic chemistry levels. Last fall, Melissa Anderson of Pasadena City College taught an honors general chemistry lab in which students did independent projects. On the first day of a multiweek titration unit, she introduced students to the various kinds of chemical and physical hazards, had them do an ac-tivity involving safety data sheets, and then had them do a titration with caustic sodium hydroxide.

Subsequently, as part of planning their independent projects, Anderson’s students completed a full hazard analysis using a worksheet Anderson developed from the ACS publication “ Identifying and Evaluating Hazards in Research Laboratories .”

The worksheet guided students through analyzing their reagents, equipment, and processes. It also asked students to consider whether substituting a different chemical or process could achieve their goals with fewer hazards. “Those questions were hard for them,” Anderson told C&EN. But she sees that challenge as an opportunity to get the students thinking more deeply about the fundamental purpose of their projects, what variables they can change for safety reasons, and which ones they can’t.

This semester, Anderson is teaching chemistry to students in allied health pro-grams such as nursing and dental hygiene, and she is thinking about how to build safety into that program. She wants to focus on the Globally Harmonized System of Classifica-tion & Labelling of Chemicals , which clas-sifies chemicals by their hazard and hazard

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 27

AD

AP

TE

D F

RO

M “

INT

RO

DU

CT

ION

TO

BO

WT

IE M

ET

HO

DO

LOG

Y F

OR

A L

AB

OR

AT

OR

Y S

ET

TIN

G”

BY

MA

RY

BE

TH

MU

LCA

HY

OF

TH

E C

HE

MIC

AL

SA

FE

TY

BO

AR

D A

ND

CH

RIS

BO

YL

AN

OF

DN

V G

L

severity. “I think it provides a really useful framework for helping students think about hazards,” Anderson said. “You want to give them tools to reach an informed perspective instead of thinking that everything is always safe or always dangerous.”

Seattle University has also been working to increase its safety education starting from general chemistry, through what the chemistry department calls a “safety teams” approach that started several years ago ( J. Chem. Educ. 2010, DOI: 10.1021/ed100207d ). Beginning in their second quarter of general chemistry, students are divided into teams of three or four students, separate from their lab experiment partners. For one lab each quarter, each team is assigned to be an extra set of eyes in the lab: The teams do a prelab inspection to make sure all students have appropriate clothing and personal protec-tive equipment (PPE), backpacks are out of the way, and safety equipment is available. During the lab, each safety team member pe-riodically walks around to ensure that PPE is still in place, hood sashes are at the right lev-el, reagents are capped, and waste bottles are

not overfilled. At the end of the lab, safety team members ensure that everything is put away, benches and balances are clean, and equipment is in good condition.

At the start, “some students are hesitant to call out their peers,” Andrea Verdan told C&EN. “But once the first group gets through, it goes smoothly.”

“The purpose is not to make students responsible for everyone else’s safety behavior but to give the class a sense that we’re all accountable for safety,” said chemistry professor P. J. Alaimo .

In Seattle’s organic chemistry labs, in-structors keep up the safety teams approach, but they add a responsibility: Teams must also do a hazard assessment of the lab for which they’re responsible. The assessment tasks include creating a safety handout, submitting it to the instructor to review in advance, and presenting a safety briefing to classmates at the start of the lab. “Students really feel like they’re part of something im-portant,” Alaimo said. Also, “we never ever saw students having safety conversations with each other prior to implementation of

this program. Now it’s almost as common as ‘What do we do next?’ ”

The students’ training in general and organic labs then carries over to upper-level labs and research projects. Although Seattle professor Ian Suydam doesn’t have students do a safety briefing for his physical chemis-try lab—the concerns are more instrumental rather than chemical and harder for the stu-dents to research in advance—he believes that the earlier experiences prime students to think and ask about safety concerns.

And when students start research proj-ects, “I know exactly what they’ve seen before and that makes it easier to train them in my lab,” Suydam said. “I think it would be so much more work and I’d be so much more worried if they hadn’t had that introduction.”

“Our students know they can’t run a re-action without knowing the reagent’s prop-erties, or they can’t decide how to measure something out unless they know its phase and toxicological concerns,” Alaimo said. “We want them to be able to walk into grad school or a job ready to go.” ◾

Spill or splash

NO2 release

Violent reaction from nitric acid + organic reagent

Spill cleanup

Quantity limit

Fume hood

Emergency shower

Eyewash

Skin damage

Eye damage

Lung damage

Personal protective equipment

Hot plate with magnetic stirrer

Personal protective equipment

Uncluttered fume hood with no obstructions

Clean glassware and storage bottles free of organic residue

Spill kit with neutralizing material

Caustic chemicals

Skin, eye, or lung

contact

Hazard

Consequence

Threat

Barrier

Loss-of-control event

A way to assess risk One risk assessment tool that could help students and others think through their experiments is the “bowtie” method. This method was presented at the ACS meeting in San Diego by Mary Beth Mulcahy , an inves-tigator at the Chemical Safety Board, and Chris Boylan , head of the safety systems risk section at risk management company

DNV GL. The example shown here is for preparing a stock solution of copper(II) nitrate by using concentrated nitric acid to digest copper wire.

The general concept of the bowtie is to identify a particular hazard of an operation, such as using a corrosive reagent. Then you predict a critical event in which you’ve lost control of

that hazard, such as spilling the reagent. The hazard and loss-of-control event go in the center of the diagram.

You work right from the cen-ter to identify and list potential consequences of the loss-of-control event, such as chemical burns and lab damage, as well as the barriers that would help prevent or mitigate the conse-quences. You work left from the center to identify and list the

threats that could lead to the event, such as a spill or organic residue left in a beaker, as well as the barriers that would help keep the threat from turning into the full-blown event.

A bowtie diagram by itself is “a tool for communication, not hazard identification,” Boylan emphasized, although a bowtie exercise could include checking safety data sheets or other re-sources to identify hazards.

28 C&EN | CEN.ACS.ORG | APRIL 18, 2016

Plant-e, a Dutch company spun off in 2010 from Wageningen University, has a vision that one day the rhizosphere, or soil root

zone, won’t just provide plants with water and nutrients. It will provide people with electricity.

To some, the idea will seem implausible. But Plant-e, with a staff of just five, has al-ready proven the concept with a demonstra-tion project that powers LED safety lights on a road barrier. With refinements, the company hopes to develop a system cheap enough for small farmers in developing countries to generate their own electricity.

The idea came from founder David Strik,

assistant professor of biology at Wagenin-gen, whose expertise includes microbial fuel cells, and the company’s chief execu-tive officer, Marjolein Helder, whose Ph.D. was on generating electricity from plants.

The electricity that Plant-e seeks to har-vest is generated in tiny amounts in the rhi-zosphere by microbes of the Geobacter and Shewanella genera. These microbes, which thrive in wet, anaerobic conditions, con-sume organic matter released by plant roots and then jettison electrons into the soil.

“We provide the electron acceptor,” says Pim de Jager, Plant-e’s engineer, who works on the project in labs rented from the university. P

LA

NT

-E

ENERGY

C&EN profiles Plant-e, a start-up looking to soil for power Dutch university spin-off seeks to capture electrons from microbes living alongside plant roots

ALEX SCOTT , C&EN LONDON

The latest version of the firm’s technolo-gy is an anode tube about 5 cm wide and up to several meters long made mostly from an activated carbon-based felt. The cathode is inserted inside.

The system is buried in the soil, leaving crops to be planted and harvested as usual. “No one will notice anything apart from a couple of wires,” de Jager says.

Micropores on the surface of the acti-vated carbon are large enough for the soil microbes to grow in. The bacteria grow “nanowires” inside the pores that connect with the activated carbon and enable the bacteria to release electrons to the anode.

The firm’s long-term goal is for 1 m 2 of

soil to yield 3 W of power, up from the 1 W it is currently generating in the lab. At this higher rate, about 125 m 2 of suitable land could power an average family home in the Netherlands.

The company still has a way to go. A sys-tem Plant-e installed near Wageningen in November 2014 successfully powers LED warning lights on a road barrier. Based on an older modular technology, it only gen-erates a “couple of watts” from a soil area of 100 m 2 , de Jager acknowledges. And each 1-meter tube currently generates just milli-watts of power.

The firm’s progress is encouraging, argues Jason He, an associate professor at

Virginia Tech, whose own research includes using microbes both to decontaminate wastewater and harvest energy from it . One challenge is that ion movement is greatly limited, He says, resulting in an insufficient supply of electrons and subsequent limited electricity generation.

Plant-e is confident that better materials and a greater understanding of soil condi-tions will lead to significant increases in power output.

A future research focus will be determin-ing optimal pore size on the anode surface. If the pores are too small, the firm thinks, the microbes may not be able to fit their nanowires inside them. The firm plans to investigate the use of carbon grains and graphite in place of the activated carbon felt in case their pore sizes are a better fit for the bacteria. “Whatever it is, it has to be cheap,” de Jager says.

To better understand how to improve the technology, late last year the firm began testing 30 variously configured systems in a waterlogged, western region of the Nether-lands. The electron-harvesting tubes are be-tween 1 and 2 meters in length. In a second trial, the tubes will be about 15 meters long.

In addition to generating electricity, Plant-e’s technology could promote the growth of electricity-generating soil bacte-ria at the expense of methanogens, bacteria that excrete the potent greenhouse gas methane. About 25% of global methane emissions are emitted by methanogens in rice paddies. Curbing such emissions could be eligible for payments from United Na-tions carbon reduction schemes. “If we can put a value on that, it’s a whole different ball game,” de Jager says.

Much of Plant-e’s funding, totaling just a few hundred thousand dollars, is from aca-demic research grants. The firm has opted to take this route and maintain full control rather than recruit outside investors to ac-celerate its research. In the past few years, according to de Jager, it has rejected a num-ber of advances from private investors and venture capitalists.

It might take some time before a com-mercially viable product is ready, but Plant-e is convinced it will be worth the wait. “It could provide farmers with power in some of the poorest regions of the world and even provide them with income,” de Jager says. ◾

Plant-e’s technology is successfully deployed in the Netherlands to power LEDs on a road barrier.

Plant-e at a glance

▸ Headquarters: Wageningen, the Netherlands

▸ Company focus: Technology for generating electricity from soil microbes

▸ Funding: A few hundred thousand dollars, mostly from academic grants

▸ Employees: Five ▸ Legal status: Plant-e is an

independent, privately held company

Antroquinonol A: Scalable Synthesis and Preclinical

Biology of a Phase 2 Drug Candidate

Phil S. Baran et al.

DOI: 10.1021/acscentsci.5b00345

EXAMPLES OF

THE EXCEPTIONAL

IN ORGANIC CHEMISTRY

To submit your next great discovery visit

pubs.acs.org/acscentralscience

ACS Central Science publishes high impact organic chemistry research. This list of articles

highlights some of the articles that we published in the past year. We welcome the submission

of your next great discovery to ACS Publications’ first open access chemistry journal that is

FREE TO PUBLISH AND FREE TO READ.

ORGANIC CHEMISTRY HIGHLIGHT ARTICLES

Cobalt(III) Werner Complexes with 1,2-Diphenylethylenediamine

Ligands: Readily Available, Inexpensive, and Modular Chiral Hydrogen

Bond Donor Catalysts for Enantioselective Organic Synthesis

John A. Gladysz et al.

DOI: 10.1021/acscentsci.5b00035

High-Potential Electrocatalytic O2 Reduction with Nitroxyl/NO

x

Mediators: Implications for Fuel Cells and Aerobic Oxidation Catalysis

James B. Gerken and Shannon S. Stahl

DOI: 10.1021/acscentsci.5b00163

Remote Meta-C–H Activation Using a Pyridine-Based Template:

Achieving Site-Selectivity via the Recognition of Distance and Geometry

Jin-Quan Yu et al.

DOI: 10.1021/acscentsci.5b00312

30 C&EN | CEN.ACS.ORG | APRIL 18, 2016

BRITT E. ERICKSON , C&EN WASHINGTON

Silicone wristbands reveal personal exposures to toxic compounds

Tracking everyday chemical exposures

In brief Simple, lightweight silicone wristbands are giving researchers a new window on people’s environmental expo-sures to toxic organic chemicals. They sequester and concen-trate organic compounds, with a chemical absorption profile similar to that of human cells. And unlike other devices for tracking chemical exposure, the wristbands are comfortable to wear. Read on to find out how scientists are using them to ex-plore links between disease and exposure to pesticides, flame retardants, fragrances, and en-docrine disruptors.

Cover story

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 31

For one week, 92 preschool-aged children in Oregon sported colorful silicone wristbands provided by researchers from Oregon State University. The children’s parents then returned the bands, which the researchers analyzed to determine whether the youngsters had been exposed to flame

retardants. The scientists were surprised to find that the kids were exposed to many polybrominated diphenyl ethers (PBDEs), chemicals that are no longer produced in the U.S., as well as to organophosphate flame retardants, which are widely used as substitutes for PBDEs.

WIL

L L

UD

WIG

/C&

EN

/SH

UT

TE

RS

TO

CK

The results from that wristband study ( Environ. Res. 2016, DOI: 10.1016/j.envres.2016.02.034 ) remain qualitative—they tell parents whether their child has been exposed to a particular chemical but don’t pro-vide information regarding the amount of exposure. The researchers, led by environmental chemist Kim Anderson , are now working on ways to extract quan-titative exposure data from the bands.

The work by Anderson’s team is one of several projects evaluating the effectiveness of silicone wristbands to record exposure to organic chemicals in air, water, and personal care products. Interest in using the bands as personal exposure monitors has been growing since Anderson’s team described the technology in a 2014 Environmental Science & Tech-nology study (DOI: 10.1021/es405022f ). Increasing demand for the wristbands recently led Anderson to cofound MyExposome, a company that hopes to put the tool into the hands of the public.

A simple wearable Silicone wristbands are easy to slip on, light-

weight, and comfortable to wear compared with traditional personal air monitoring devices that rely on bulky air pumps, filters, and electronics. Study participants wear the bands for a specific amount of time—typically a day, a week, or a month. They keep the bands on at all times during the study—while sleeping, showering, jogging, swimming, eating, working, petting the dog, or reading their favorite magazine.

While they are being worn, the bands passively absorb a wide range of organic chemicals from the participants’ surroundings, trapping them within the silicone polymer matrix. After participants return the bracelets, researchers extract chemicals from them using various solvents or thermal desorption methods.

They identify the substances using analytical methods such as gas chromatography/mass spec-trometry. Anderson’s team has developed a GC/MS screening method that detects 1,400 organic chemi-cals from wristbands, including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, pesticides, flame retardants, fragrances, and en-docrine-disrupting chemicals such as bisphenol A, phthalates, and nonylphenol. The number of chemicals that the method detects keeps growing, Anderson says.

The screening method provides qualitative in-

formation on whether the chemicals are present in the wristband. It does not provide information on the amount of each chemical. But Anderson and colleagues are working to change that. They have already developed quantitative methods for ana-lyzing certain classes of chemicals, including PAHs, pesticides, and flame retardants, absorbed into the wristbands.

Anderson got interested in silicone wristbands after decades of work in the environmental field developing passive sampling technologies. Such technologies measure how much of an environmen-tal pollutant is likely to end up in an organism, rather than how much of the substance is in water, sedi-ment, or air. Merely determining the concentration of chemicals in the environment “is a poor surrogate for understanding the chemical load in organisms,” she says.

While attending a football game years ago, Ander-son noticed that several athletes and fans were wear-ing silicone wristbands. “I knew that was a material that I could adapt to be a passive sampler,” she says.

Her research group had previously tried to make a passive sampler necklace. It was effective in some regards, but wasn’t amenable to some job environ-ments in which workers could be endangered by an item dangling around their necks. It also wasn’t expected to be something men would be willing to wear, Anderson notes. So she and her colleagues began developing gender-neutral wristbands out of various carbon- and silicone-based polymers.

Silicone polymers are an attractive material for wristbands because they are more elastic than poly-mers made from carbon, Anderson says. Silicone polymers are also good mimics of bioavailability because they contain long chainlike structures that form spaces similar in size—about 1 nm in diam-eter—to pores created by biological polymers in a human cell membrane, she says.

The wristbands are being promoted to the public by the Environmental Defense Fund (EDF), an environmental group that teamed up with MyExposome on a small project last year. EDF recruited 28 volunteers, mostly EDF staff and board members, to wear the bands for one week. Partici-pants filled out a short activities survey. MyExposome analyzed their bands qual-itatively for the suite of 1,400 chemicals.

EDF reported 57 chemicals were found in the bands, including PAHs, pesticides, plas-

32 C&EN | CEN.ACS.ORG | APRIL 18, 2016

ticizers, phthalates, fragrances, preserva-tives, and flame retardants. Each band con-tained at least 10 and as many as 27 of the screened chemicals , with an average of 15.

The environmental group has since recruited a more geographically diverse group of volunteers, representing all 50 states and some international regions, to further test the wristbands. “We have now about 5,000 people who have signed up,” says Sarah Vogel, vice president of health programs at EDF.

Exposure matters The bands have already made a dif-

ference for roofers in western Oregon, Anderson tells C&EN. A small group of the roofers wore the wristbands while working as part of a pilot project conducted by An-derson and colleagues at Oregon State to determine whether the bands can be worn comfortably by workers who are physically active on the job.

When the researchers analyzed the chemicals in the bands, they discovered that roofers at a training location were exposed to higher levels of harmful PAHs than roofers at a job site. Even though it was just a small demonstration project, the data were compelling, Anderson says. The researchers communicated the informa-tion to the roofers’ union, which prompted changes in how the workers set up tar ket-tles—a source of PAHs—and how the train-ing site is ventilated.

The bands are also helping researchers

examine whether there is a link between prenatal exposure to hazardous PAHs and asthma in children. Anderson is collabo-rating with Julie Herbstman, an epidemiol-ogist at Columbia University, on a project with pregnant women in New York City.

“We put the wristbands on the women in their last trimester,” Anderson says, and later follow their children’s health for asth-ma and other adverse effects. The pregnant women also provide urine samples and wear conventional backpack polyurethane foam air samplers to monitor their expo-sure to PAHs.

The project just started last year, so it is too soon to tell if prenatal exposure to PAHs is associated with asthma in chil-dren. “You can’t really diagnose asthma until children are two to three years old,” Anderson notes. But the wristband results do seem to correlate well with PAH metab-olites found in urine, Anderson says. The wristbands are more comfortable to wear, have lower cost, and are less of a burden to set up and operate than the backpacks.

In other work Anderson and colleagues are conducting, exposure data from sili-cone wristbands are integrated with loca-tion data from a smartphone’s GPS and measurements of lung function taken with a pocket-sized spirometer. The studies aim to associate exposures to toxic PAHs with decreased lung function.

In one study, 10 adults with asthma in Eugene, Ore., each wore a wristband for one day and then wore a second band for one week. The smartphone pinged them three

times a day as a reminder to take a lung function measurement with the spirome-ter, which was connected by Bluetooth to the phone. Afterward, researchers at Pacif-ic Northwest National Laboratory down-loaded the data and integrated them with chemical data from the wristbands.

Preliminary results suggest that lung function decreases on days associated with exposure to high levels of PAHs, Anderson says. But in some cases, the effect lags. “What you are exposed to the day before affects your lung function the next day,” she notes.

Flame retardants in children Silicone wristbands are also helping

researchers study the link between flame retardants found in electronics, furniture, and textiles, and adverse health effects, particularly in children. Heather M. Sta-pleton and colleagues at Duke University have been exploring such associations for more than a decade by measuring chemi-cals in the air and in house dust. They have also used hand wipes to examine hand-to-mouth exposure and dermal contact. When the researchers learned about the wristbands, they put them to the test to see how they compare with the hand wipes. The results were published last month in Environmental Science & Technology (2016, DOI: 10.1021/acs.est.6b00030 ).

“We examined how the levels of organo-phosphate flame retardants on hand wipes and wristbands compared to urinary metab-olites of those compounds,” says Stephanie C. Hammel, a graduate student in Staple-ton’s group at Duke. The study involved 40 participants who wore the wristbands for five consecutive days and collected urine samples on days one, three, and five. They used hand wipes on day five. Urine samples were pooled across the three days and ana-lyzed for metabolites of four organophos-phate flame retardants: tris(1,3-dichloroiso-propyl) phosphate (TDCIPP), tris(1-chloro-2-propyl) phosphate (TCIPP), triphenyl phosphate (TPHP), and monosubstituted isopropylated triaryl phosphate (mono-ITP ).

“For the compounds where we saw a significant correla-tion, the wristbands were more highly correlated to the urinary metabolites than the hand wipes,” Hammel says. “We believe that the wrist-bands work better as a more time-in-tegrated measure of exposure—or H

OL

LY D

IXO

N/O

RE

GO

N S

TA

TE

U (

EX

PO

SU

RE

KIT

)

Data from a portable spirometer (far right) that measures lung function is being integrated with location data from a smartphone’s GPS and exposure data from a silicone wristband to explore whether chemical exposure affects lung function.

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 33

How silicone wristbands act as personal exposure monitors Silicone wristbands absorb organic chemicals from the environment. The bands can be worn at all times and continue to record a per-son’s chemical exposure even as they sleep, shower, jog, swim, eat, work, pet a dog, or perform any other activity.

Silicone polymers mimic the way human cells absorb organic chemicals because they contain long chainlike structures that create chan-nels similar in size (about 1 nm) to pores created by biological polymers in a human cell membrane. The wristbands take up polycyclic aromatic hydrocarbons, polychlorinated biphenyls, pesticides, fl ame retardants, fragrances, endocrine-disrupting chemicals, and many other persistent pollutants. The chemicals can be extracted from the bands and analyzed, providing a snapshot of an individual’s chemical exposure over a particular time period.

at least in this case a period of five days —whereas hand wipes might reflect more recent exposures,” Stapleton adds.

On the farm in Africa The wristbands have caught the attention

of researchers around the world. Projects are under way in Africa, Asia, Europe, and the U.S. to evaluate the bands for use in mon-itoring farm and worker-related chemical exposures, Anderson says.

Paul Jepson, director of the Integrated Plant Protection Center at Oregon State, and scientists in Anderson’s group are col-laborating to help residents of a rural farm-

ing community in Senegal learn about their chemical exposures.

“We’ve been working with the communi-ty for about a decade or more with stationary air monitors,” Anderson says. “They had heard about the wristband and asked us if they could wear them as part of a study.”

The Oregon State researchers recruited 35 men and women from the community to each wear a band for five days. Afterward, they were given a second band to wear for another five days. The researchers then analyzed the bands quantitatively for 63 pesticides. Each person’s band had two to 10 pesticides, but no two individuals had the same profile. The amounts of pesticides in

the bands within the same individual were consistent from the first week to the second.

Differences such as this in pesticide ex-posure from one individual to the next are not captured by stationary air monitors, which are often used to calculate exposures, Anderson stresses. On the basis of the infor-mation provided by the wristbands, she says it may be important to customize advice to individual farmers about how to reduce their exposure to pesticides.

Although this was a small study, it demon-strates the eagerness of people to use this technology, Anderson says. The researchers observed 100% compliance—participants wore the bands as they were instructed.

P

S

O

O ONCl

Cl Cl

Chlorpyrifos

Pesticides

Galaxolide

O

Fragrances

HO OH

Bisphenol A

Endocrine-disruptingchemicals

Polybrominated diphenyl ethers

O

Brm Brn

Flame retardants

Benzo[a]pyrene

Polycyclic aromatic hydrocarbons

Clm Cln

Polychlorinated biphenyls

C&

EN

/SH

UT

TE

RS

TO

CK

34 C&EN | CEN.ACS.ORG | APRIL 18, 2016

That’s not been the case with conventional personal-backpack monitors, she says.

High-throughput exposure modeling

Scientists at the U.S. Environmental Protection Agency are excited about the flurry of research under way using silicone wristbands for monitoring everyday ex-posures to chemicals. EPA and the world’s other regulatory agencies need both ex-posure and toxicity information to assess the risk of a chemical. But there are many chemicals for which exposure data simply don’t exist.

“If we can identify hundreds or thou-sands of chemicals in a wristband that we didn’t know people were being exposed to, that is a treasure trove,” says John Wam-baugh, a physical scientist with EPA’s Of-fice of Research & Development.

Wambaugh sees one limitation to the wristbands: They provide only a record of a person’s cumulative exposure over time. “You lose some of the notion: Did they get one big exposure at one point, or have they been gradually getting exposure?” he says.

Still, he is excited to examine how the wristbands could complement an ongoing EPA effort to develop computer models that generate high-throughput exposure predictions for thousands of chemicals. Initially, the models were based on data about how chemicals are used, says Kristin Isaacs, an EPA scientist who works with Wambaugh.

“We needed information about what chemicals are in consumer products and at what concentrations,” Isaacs says. So a few years ago, the EPA scientists began collecting data for about 2,000 chemicals that are listed on product material safety data sheets made publicly available by re-tail giant Walmart. They then merged that information with what they could find in scientific literature about how people use consumer products.

EPA has entered into collaborations to get more data on consumer product use. For example, EPA scientists have access to product-use questionnaires for 50,000

women enrolled in the Na-tional Institutes of Health’s

Sister Study—a study following the health of women whose sister had breast cancer.

EPA also has an agree-ment with Nielsen, a company that provides information on what television shows con-sumers watch and what

they buy. The company pro-vided EPA with a year’s worth of data from 60,000 households involved in a project in which people record every product they bring into their homes. “We are analyzing those data to see if we can predict what people are buying based on de-mographics,” Wambaugh adds.

Although EPA now has more data than ever on chemicals in consumer products, the agency still lacks informa-tion about thousands of substances. In a recent test, EPA scientists ground up 100 consumer products, including upholstery, breakfast cereals, and baby toys, and tried to extract every chemical they could.

The researchers found 3,800 different chemicals, and only 2,000 of those were ones that they already knew were in con-sumer products, Wambaugh says. The unidentified substances might not raise concerns, however. “Unless you are grinding your baby toy up in a blender and extracting

it with dichloromethane, you are not neces-sarily being exposed,” he says. “But the po-tential is there .” The wristbands could help EPA identify whether people are actually being exposed to any of the chemicals.

Identifying chemicals in pulverized consumer products, house dust, silicone wristbands, or any other matrix can be chal-lenging if researchers don’t know what they are looking for. Advances in high-resolution mass spectrometry, coupled with more data on how people use various consumer prod-ucts, however, are facilitating the process.

High-resolution MS has been a boon to exposure science over the past few years, Wambaugh says. “It allows you to try to identify everything in the sample,” he notes. In the past, scientists would analyze a sample, such as blood, urine, or dust, for a specific chemical. That work was predi-cated on researchers knowing which sub-stance they were looking for.

But even with high-resolution MS, identifying specific chemi-cals can be tricky. That’s because

different molecules can consist of the same atoms combined in dispa-

rate arrangements. EPA scientists recently ran into

that situation when trying to iden-tify chemicals in house dust from dozens of homes across the U.S.

The researchers detected a compound with the molecular formula C 17 H 19 NO 3 in 75% of the dust samples. Initially, they thought they had uncovered a huge heroin problem be-cause the molecular formula matches that of morphine, a component of heroin. But the formula also matches piperine, the alkaloid that gives black pepper its pungency.

The EPA scientists then examined infor-mation about how each of these two chem-icals is used and combined those data with exposure predictions from high-throughput models. “We decided that most of those matches were actually the black pepper ingredient rather than the heroin compo-nent,” Wambaugh says, because many more people use black pepper than heroin.

EPA scientists are currently working with university researchers and technology com-panies to develop methods for screening blood samples for new chemical signatures using nontargeted high-resolution MS. Sili-cone wristbands could simplify the analysis.

“It is much easier to analyze a wristband for a wide range of chemicals than it is to analyze a blood sample for a wide range of chemicals,” Stapleton says. “The matrix isn’t as complicated.”

Wambaugh sees great potential in people using silicone wristbands to record their chemical exposure. He acknowledges that the bands are an imperfect tool, but he says they have fewer limitations than other methods routinely used to evaluate risk, such as toxicity tests on laboratory rats.

Consumers who want to learn about their everyday exposures to chemicals can try out the wristbands by joining projects such as those conducted by EDF. MyExposome eventually hopes to market the bands direct-ly to the public. But for now, the company only offers them to groups of 20 people or more, at a cost of about $1,000 per person.

Anderson is hoping to get funding for a citizen science project using the wrist-bands. “You don’t have to wait for a disas-ter like a Flint” for people to get interested about their chemical exposures and want to wear the band, she says, referring to the lead-in-drinking-water crisis in Flint, Mich. “We have developed a technology that inspires people to think about science and their environment and hopefully even act about their environment.” ◾

“It is much easier to analyze a wristband for a wide range of chemicals than it is to analyze a blood sample for a wide range of chemicals.”

— Heather Stapleton , Duke University

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 35

ACSNEWS

Chemists, the chemistry enter-prise, and the American Chemical Society operate in a fast-paced, increasingly uncertain, and

rapidly changing world. We have much to contribute through solutions that will help achieve the ACS vision of “improving people’s lives through the transforming power of chemistry.” The burning question is “How can we navigate this environment suc-cessfully to have lasting and significant impact?” The short answer is “Be thoughtful and strategic about what we do and how we do it.”

There is a simple, powerful thought pro-cess to demystify how to be thoughtful and strate-gic. The process has four main steps that move us to strategically focused actions based on forces in the world outside us. It works equally well for individuals; for groups such as ACS local sections, divisions, and commit-tees; and for ACS as a whole. Here are the steps: (1) Observe the world and identify major trends that might affect us.(2) Eval-uate what opportunities or challenges these trends create. (3) Determine what actions we might take to respond to these opportunities and challenges. (4) Choose and pursue a realistic number of the most promising options.

At the society level, part of the answer to the “how” of being strategic has been to create an ACS Board Standing Committee on Planning. The planning committee serves as a focal point for strategic think-ing and planning prior to full ACS Board discussion and action. The planning com-mittee’s charter is purposefully broad. His-torically, the committee focused on recom-mending the next year’s ACS Strategic Plan to the ACS Board, but given the challenges for ACS in today’s world, is this enough?

To answer that and other strategic ques-tions about the planning committee, we followed the lead of more than 30 ACS units that have held a Strategic Planning Retreat

during the past three years and held a facil-itated strategic planning session last fall. The retreat, part of the ACS Leadership De-velopment System, freed us of day-to-day pressures, allowing us to be thoughtful and strategic and to determine what the plan-ning committee should do to help ACS have maximum impact in today’s world.

We developed the following vision of long-term success for the planning committee: “A dynamic and successful ACS through strategic planning and action.” Using this vision as a North Star, we developed our mission statement: “Develop, communicate, and promote a strategic process and plan that en-gages staff and volunteer leaders, aligning their efforts to realize the ACS vision.”

These vision and mis-sion statements, featuring words and phras-es such as “action,” “develop, communicate, and promote,” “engage staff and volunteer leaders,” and “align efforts,” make it clear that the planning committee’s responsi-bility is to do more than recommend next year’s ACS Strategic Plan to the ACS Board. With the board’s approval, the planning committee’s work now includes two goals: (1) Develop and continuously improve the ACS strategic planning process, and (2) Develop and implement a communications plan that facilitates communication with key stakeholders.

So what’s happening now? The planning committee has broadened its focus to find and implement tools and practices for stra-tegic planning, identification of emerging trends, and “futures thinking,” which helps groups envision possible futures and gain new insights. We are using increased dia-logue within the society along with external resources to guard against becoming an echo chamber.

First, the committee is actively partner-ing with ACS Executive Director and Chief Executive Officer Thomas Connelly and his team, the ACS director of strategy, and

the ACS Board to identify state-of-the-art best practices and resources for organiza-tions similar in size and type to ACS. Using this information, we hope to increase the capability of an integrated team of board members and ACS staff to think and act strategically. In January, the committee sponsored an interactive webinar and dis-cussion for the ACS Board-staff team on futures thinking with an external expert. During the next six months, we will use new guidelines to prepare for ACS Board strategic discussions that are data-driven and more productive.

Second, we will strengthen communica-tion of ACS strategic planning information by, for example, continuing to provide in-formation on the latest trends to ACS units’ strategic planning retreats; adding review of emerging trends identified in local section, division, and committee retreats for possible dissemination to the rest of ACS; and incorporating more dialogue on emerging trends with ACS committees and other units.

What are we learning about being strate-gically successful? That effective strategic planning and action requires constant vigilance to escape the pull of day-to-day, tactical pressures. Some other success factors include creating a focal point for strategy (a person or subgroup whose pri-mary responsibility is to focus on strategy), making time to be strategic (schedule it!), learning and practicing thinking strate-gically, getting organized to act (create a vision, mission, goals, infrastructure, and process to support action), and, perhaps most important, discussing “being strate-gic” with others to share what you’re learn-ing and learn from them.

Please share your thoughts on how ACS can be strategically successful in today’s world at strategy@acs.org. The planning committee welcomes your ideas and sug-gestions on the current ACS Strategic Plan and planning process, especially emerging trends affecting our work and options for better serving our members and the chem-istry enterprise.

CO

UR

TE

SY

OF

KA

TH

LE

EN

SC

HU

LZ

COMMENT

Keeping ACS strategic in an uncertain world KATHLEEN M. SCHULZ, CHAIR , ACS BOARD STANDING COMMITTEE ON PLANNING

Views expressed on this page are those of the author and not necessarily those of ACS.

36 C&EN | CEN.ACS.ORG | APRIL 18, 2016

ACSNEWS

▸ Zafra Lerman wins Andrei Sakharov PrizeFor her outstanding leadership and achieve-ments upholding human rights, Zafra Lerman has been named the recipient of

the 2016 Andrei Sakharov Prize. The $10,000 prize, awarded by the American Physical Society, was pre-sented on April 17 at an APS meeting in Salt Lake City.

An accomplished chemist, science

educator, and humanitarian, Lerman is the creator of, as well as the chair of the organiz-ing committee for, the biennial Malta Con-ference , which takes place every two years and promotes international scientific coop-eration and diplomacy as a bridge to peace in the Middle East. The conference brings scientists from 15 Middle Eastern nations to-gether with several Nobel Laureates to solve regional problems, establish cross-border collaborations, and build relationships of trust, especially between Israelis and Palestinians.

Lerman is a fellow of the American Chemical Society, the American Associa-tion for the Advancement of Science, the International Union of Pure & Applied Chemistry, and the Royal Society of Chem-istry. She plans to donate the prize money to the Malta Conference.

▸ Florida Award to Richard AdamsRichard D. Adams, Carolina Distinguished Professor in the department of chemistry and biochemistry at the University of South Carolina, is the recipient of the Florida Award, presented by the ACS Florida Section.

The award recognizes leadership and contributions toward the advancement of the profession of chemistry. Adams is being honored for his more than 30 years of contributions to the organometallic chem-istry of polynuclear metal complexes and their catalytic transformations of a variety of small molecules. He is also being rec-ognized for his service to the community through editorial and conference organiza-tional activities.

▸ Inorganic Nanoscience Award to Raymond Schaak Raymond E. Schaak, DuPont Professor of Materials Chemistry at Pennsylvania State University and an associate editor at ACS Nano, is the winner of the 2016 Inorganic Nano-science Award, presented by the ACS Division of In-organic Chemistry to honor excellence in research. The award is sponsored by the NanoCenter at the University of South Carolina.

Schaak is well-known for his creative

▸ Nominations sought for Pauling MedalNominations are being accepted for the 2016 Linus Pauling Medal Award. Spon-sored jointly by the American Chemical So-ciety’s Puget Sound, Oregon, and Portland local sections, the award is presented annu-ally in recognition of outstanding achieve-ment in chemistry in the spirit of and in honor of Linus Pauling, a native of the Pacif-ic Northwest. The medal will be presented at a symposium to be held this fall at Pacific Lutheran University in Tacoma, Wash.

Nominations should consist of a concise curriculum vitae that lists significant pub-lications, honors, and awards, along with a summary (400–1,000 words) of scientific achievements, including explanations that clearly outline the importance of the nominee’s work.

E-mail a single pdf that includes all nomination documents by May 23 to pauling2016@chem.plu.edu with “nomination” in the subject head. For details, visit www.plu.edu/chemistry/pauling2016.

work in synthetic inorganic nanochemistry. His work provides new paradigms for the design and synthesis of complex inorganic nanostructures by using the concept of ret-rosynthetic design, which historically has been limited to molecular systems.

Schaak will receive the award, which consists of a plaque and $3,000, at the ACS national meeting in Philadelphia in August.

WCC names 2016 Rising StarsThe American Chemical Society Women Chemists Committee (WCC) has named the recipients of its 2016 Rising Star Awards, which recognize excep-tional early- to midcareer women chemists across all areas of chemistry on a national level. The awards were established in 2011 to help promote retention of women in science.

The winners are Karelle Aiken, Georgia Southern University; Anas-tassia N. Alexandrova, University of California, Los Angeles; Rongjuan Cong, Dow Chemical; Elise B. Fox, Savannah River National Laboratory; Susan Halpern Chirch, L’Oréal USA; Amanda B. Hummon, University of Notre Dame; Mindy Levine, Universi-ty of Rhode Island; Jin K. Montclare, New York University Tandon School of Engineering; Jennifer A. Prescher, University of California, Irvine; and Rebecca T. Ruck, Merck Research Laboratories.

The winners received a $1,000 sti-pend to cover travel expenses to the 2016 spring ACS national meeting in San Diego, where they presented their research. Nominations for the 2017 awards are due June 15. For more informa-tion, visit www.womenchemists.sites.acs.org.

Top row (from left): Ruck, Hummon, Aiken, Fox, Montclare, and Chirch. Bottom row (from left): Prescher, Alexandrova, Cong, and Levine.

Linda Wang compiles this section. Announcements of awards may be sent to l_wang@acs.org. C

OU

RT

ES

Y O

F A

MB

ER

CH

AR

LE

BO

IS

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 37

▸ ObituariesACS

NEWS

Elmer Joseph Huber Jr.

Elmer Joseph Huber Jr., 93, died on Oct. 30, 2013 , in Richland, Wash.

“Kin, as he was known by his friends, worked in explosives for the World War II effort before joining Los Alamos National Laboratory. Early work at the lab included arming devices for tower tests at the Neva-da Test Site. After the war, he worked on the thermochemistry of the actinides and laser purification of silane. He published many papers and was an invited speaker at a sym-posium in Vienna. During his 35 years at Los Alamos, he and his beloved wife, Marilyn, won many bridge championships and en-joyed a home-based business making hand-cut glass wind chimes from wine bottles. They were married for 61 years.”—Jenny (Huber) Sontag, daughter

Most recent title: chemist, Los Alamos Na-tional LaboratoryEducation: B.S., chemistry, University of California, Berkeley, 1942Survivors: daughter, Jenny (Huber) Sontag

Survivors: wife, Barbara Van Arsdale; daughters, Margaret, Amber Archer, and Ann Hinnen; son, Eric; and two grandchildren

Karl S. Vorres

Karl S. Vorres, 88, died on Aug., 7, 2015, in Tucson.

“Karl was a very active fellow who had the ability to work well with others and provide a great deal of help and under-standing. He always seemed to be happy with his role in life. He was also interested in and supportive of the ACS Division of Fuel Chemistry for over 50 years, serving as chair and preprints editor, which back in

William E. Keller

William E. Keller, 90, died on Dec. 31, 2015, in Santa Fe, N.M.

“Bill had an astute financial mind, a com-mitment to education, and a determina-tion to better the world through his charitable works and philanthropy. He passed on his passions as well as his wisdom to his children, his asso-ciates, and to many colleagues in the nonprofit world. Bill loved his garden, traveled the world, enjoyed a round of golf, excelled at stock picking, savored good food, and finished his day with a good single malt. Bill had a rich life; gave back to his community, family, and friends; and will be missed by many.”—Margaret Keller, daughter

Most recent title: division leader, Los Ala-mos National LaboratoryEducation: B.S., chemistry, Harvard Uni-versity, 1945; Ph.D., chemistry and physics, Harvard, 1948

John W. Sloan

John W. Sloan, 100, died on Jan. 5 in Cary, N.C.

“John entered the U.S. Army Medical Corps as a private in 1941 and spent a year as a chemical specialist analyzing blood and bi-

ological specimens in Camp Roberts at the California Sta-tion Hospital Clin-ical Laboratory. By the end of the war, he was a decorated Air Force captain serving as assistant wing chemical officer on Saipan

Island. In the fall of 1947, John joined the National Center for Agricultural Utiliza-tion Research of the U.S. Department of Agriculture’s Agricultural Research Ser-vice, in Peoria, Ill. In 1963, John transferred to the federal meat inspection division as assistant head of the Washington, D.C., laboratory, and the family settled in An-nandale, Va. Four years later, he became senior staff chemist for packaging materi-als and supervisor of the Beltsville, M.D., compounds laboratory. He retired from federal civil service in 1976 and began to devote more time to his lifelong hobby of photography.”—David Sloan, son

Most recent title: senior staff chemist, U.S. Department of Agriculture, Agricultural Research ServiceEducation: B.S., chemistry, Indiana Univer-sity, 1939Survivors: wife, Nadine; daughter, Jeanne; sons, Stephen, David, and Paul; five grand-children; and two great-grandchildren

Stephen L. Wythe

Stephen L. Wythe , 90, died on Nov. 13, 2015, in Knoxville.

“Born in Flushing, in Queens, N.Y., Steve was a member of U.S. Army Company H.

273rd Infantry Regiment, 69th In-fantry Division, and was stationed in Germany from 1944 to 1946. Steve was employed by Exxon Corp. from 1953 to 1982. In the 1960s, he managed the do-mestic plastics and

lubricant additives business. After retiring from Exxon in 1982, Steve ran his own con-sulting business until 1997. He spent most of his retirement years with his wife, Pat, in Pickens, S.C. He enjoyed meeting new peo-ple, astronomy, hiking, gardening, cooking, reading, travel, and history.”—Shirley Bea-sley, daughter

Most recent title: consultantEducation: B.A., science, 1950; Ph.D., organic chemistry, Columbia University, 1954Survivors: daughter, Shirley Beasley; sons, Stephen, David, Scott, and Christopher; 12 grandchildren; 15 great-grandchildren; and two great-great-grandchildren

those days demanded a whole lot of effort, particularly before the expan-sion of digital computers to do the com-piling. His latest work involved serving as manager of the Premium Coal Sample Program at Argonne National Laboratory from 1984 to 1995, after which he retired to Tucson. Previously, he had served in the Army, been educated at Michigan State University and the University of Iowa, and worked at Babcock &Wilcox and the Institute of Gas Technology Institute in Chicago.”—Donald Cronauer, friend and coworker

Most recent title: senior chemist, Argonne National LaboratoryEducation: B.S., chemistry, Michigan State University, 1957; Ph.D., physical chemistry, University of Iowa, 1958Survivors: wife, Nancy; daughters, Carol and Janet; sons, Robert and Steven; and five grandchildren

To recognize your late loved one or colleague, submit obituary information at cenm.ag/obits .

To advertise in the C&ENjobs section, please contact Kimberly Mallory via email at classifi eds@acs.org or telephone at (202) 452-8918. Please see below

for current advertising options and how to get started.

Classifi ed Line Ads (best for posting a job): Want to appear within a section with head-ers that are classifi ed according to your in-dustry? Our Classifi ed Line Ad section gives you that opportunity. Your ad can appear with text only, or you may opt to include your logo in color or black and white. Header position classifi cations include: Academic, Government, Pharmaceutical, and Industry. Pricing starts at $65 net per line ($650 min-imum). If your ad is also posted online at chemistryjobs.acs.org, please ask about our print discount opportunities.

Display Ads (best for branding): Looking for a way to stand out from com-petitors and win the attention of potential candidates? Display ads provide an excellent opportunity to elevate your brand, highlight multiple open positions, or both.

Classifi ed Directory Ads (best for announcements): Have something to sell? Announce? Want to promote your graduate program? Consider our directory. Header classifi cations in-clude: General Directory (Announcements, Chemical Exchange, Equipment Mart, Tech-nical Services) and Graduate Programs.

How To Get StartedTo place your ad in C&ENjobs, please send your job description in Word format to classifi eds@acs.org. Once your job description is received, you will receive a prompt response with a quote for your consideration.

Visit acsmediakit.org/cen-classifi eds/ and download the editorial calendar to fi nd the right issue for your message.

To connect with our Global Sales Team, please visit acsmediakit.org/contact/.

To connect with our Global Sales Team, please visit acsmediakit.org/contact/

RE

CR

UIT

ME

NT

AD

VE

RT

ISIN

G

pubs.acs.org/acssensors

Read the Inaugural Issue FREE

Mentora classroomfor National

Lab Day.

SHARE CHEMISTRY.START A REACTION...

www.acs.org/chemistryambassadors

Find everything you need

to get started!

Chemistry Ambassadors

38 C&EN | CEN.ACS.ORG | APRIL 18, 2016

Abbott Laboratories 25 www.abbottpharma.com

ChemBridge Corporation 24 www.chembridge.com

Lonza Biologics, Inc. IFC www.lonza.com

OriginLab Corporation 3 www.originlab.com

Spectrum Chemical Mfg. Corp. OBC www.spectrumchemical.com

This index and additional company information are provided as a service to the advertisers. We are not responsible for errors or omissions.

Classified Advertising 38–39

Subscription & Member Record Service 2016: Send all new and renewal subscriptions with payment to: ACS, P.O. Box 182426, Columbus, OH 43218-2426. Changes of address, claims for missing issues, subscription orders, status of re-cords and accounts should be directed to: Manager, Member & Subscriber Services, ACS, P.O. Box 3337, Columbus, OH 43210; (800) 333-9511 or (614) 447-3776.Subscription Rates 2016: Printed editions (1 year, ACS mem-ber): $52.98—included in the ACS membership dues of $162 for members living in North America; members living outside North America who opt to receive the print edition add $68 for shipping and handling. (1 year, nonmember individual): North America, $285; Outside North America, $353. (1 year, institu-tions): North America, $600; Outside North America, $685.Single copies: Current $25. Rates for back issues and vol-umes are available from Office of Society Services, ACS, 1155—16th St., N.W., Washington, DC 20036, or e-mail help@acs.org, or call (800) 227-5558 or (202) 872-4600.Chemical & Engineering News (ISSN 0009-2347) is pub-lished weekly except for the last week in December by the American Chemical Society at 1155—16th St., N.W., Washing-ton, DC 20036. Periodicals postage is paid at Washington, DC, and additional mailing of ces.POST MASTER: Send address changes to: Chemical & Engi-neering News, Member & Subscriber Services, P.O. Box 3337, Columbus, OH 43210.Canada Post Mail Agreement Number: 40612608ACS assumes no responsibility for the statements and opin-ions advanced by the contributors to its publications.C&EN is published in print format, and may be published in other formats, methods, and technologies of distribution now known or later developed. For all illustrations submitted to and used in C&EN, it is understood and agreed that they may appear in other formats, methods, and technologies of distribution, including but not limited to reprints of the articles to which they apply.Copyright permission: Reprographic copying beyond that permitted by Section 107 or 108 of the U.S. Copyright Act is allowed for internal use only, provided that the fee of $13.00 per article copy is paid to the Copyright Clearance Center (CCC), phone +1 (978) 750-8400. Direct reprint and other permission requests to ACS Copyright Of ce, Publications Division, 1155—16th St., N.W., Washington, DC 20036. For quotes and ordering information on bulk reprints, e-mail cencopyrequest@acs.org. The CCC Code for C&EN is 0009-2347/02/$13.00.

ACS Publications' Advertising Sales Group(See list of of ces to the right)

© Copyright 2016, American Chemical SocietyCanadian GST Reg. No. R127571347

JUNE 14-16, 2016

PORTLAND, OR

REGISTER BY APRIL 29TH FOR

A DISCOUNTED RATE

WWW.GCANDE.ORG/

REGISTRATION

20th Annual Green Chemistry & Engineering

Conference

gcande.org

Advancing Sustainable

Solutions by Design

Advanced Registration

Open

APRIL 18, 2016 | CEN.ACS.ORG | C&EN 39

ACSMediaKit.org1155 16th St., NW, Washington, DC 20036

KEVIN A. DAVIES

PublisherTelephone: (202) 776-8217

k_davies@acs.org

STEPHANIE HOLLAND

Manager, Advertising and Business Development

Telephone: (202) 872-4536s_holland@acs.org

RENEE ZERBY

Manager, Advertising Production(202) 872-8069

cenc@acs.org

ADVERTISING PRODUCTION SPECIALISTS

Krystal King & Joe Davis202-872-6127

DisplayAds@acs.org

Sales Representatives:tnempoleveD lanoisseforP & tnemtiurceR …

Kimberly MalloryTel: 202-452-8918E-mail: classifi eds@acs.org

Virginia to Northeast US… Peter ManfreTel: 917-421-9077Email: p.manfre@ jamesgelliott.comJohn DayTel: 917-421-9042Email: j.day@ jamesg elliott.com

Midwest, Central & Southern US…Pegeen PrichardTel: 312-348-1204Email: p.prichard@jamesgelliott.comScott HillTel: 312-348-1206Email: s.hill@ jamesgelliott.com

Western, Pacific US & Canadian Sales…

Tel: 213-596-7202Email: d. gentilella@ jamesgelliott.com

dnalreztiwS & ynamreG ,eporuE lartneC …

Tel: 49-202-271-690E-mail: riemeyer@ inter media part ners.de

,ylatI ,dnalerI ,ecnarF ,muigleB ,modgniK detinUPortugal, Scandinavia, Spain & the Middle East…Paul Barrett, Hartswood MediaTel: 44 1268 711 560E-mail: paulbarrett@hartswood media.com

China…eChinaChem, Inc.Tel: 86 21 5169 1611E-mail: angel.zhu@echinachem.com

Japan…Shigemaro Yasui, Mai Hashikura, Global Exchange Co., Ltd.Tel: 81-3-5733-5031E-mail: mai@global-exchange.co.jp

India…Faredoon Kuka, RMA MediaTel: 91 22 6570 3081E-mail: info@rmamedia.com

Korea…DOOBEE Inc., Tel: 822 3702 1700E-mail: dbi@doobee.com

Singapore…Peggy Thay, Publicitas Singapore Pte. Ltd.Tel: +65 6836 2272E-mail: peggy.thay@ publicitas.com

Thailand…Publicitas ThailandTel: 662-651-9273-7E-mail: ppn-thailand@ publicitas.com

INDEX TO ADVERTISERS IN THIS ISSUE

40 C&EN | CEN.ACS.ORG | APRIL 18, 2016

NewscriptsCurating quirky science since 1943

Newton’s alchemical studies

Study: Isaac Newton left notes inside square brackets in this hand-copied alchemical manuscript.

CH

EM

ICA

L H

ER

ITA

GE

FO

UN

DA

TIO

N (

MA

NU

SC

RIP

T);

C&

EN

/SH

UT

TE

RS

TO

CK

(S

NIF

FE

R)

Craig Bettenhausen wrote this week’s column. Please send comments and suggestions to newscripts@acs.org.

Alchemists of old sought to convert base metals into gold. Though the efforts were unsuccessful and the practices tinged with forbidden ties to the occult, scientists as

far back as Isaac Newton saw real scientific value in alchemical data, methods, and equipment.

The Chemical Heritage Foundation (CHF) recently acquired a manuscript in which Newton hand-copied

a text by chemist George Starkey. Starkey was born in Bermuda, educated in New England, and later became a prominent figure in London’s chemistry community. Howev-er, the text is written under Starkey’s alter ego, Eirenaeus Philalethes, which he used to publish alchemical works without risking his professional reputation.

Starkey, writing as Philalethes, de-scribes the prepa-ration of sophic mercury, a substance purported to break metals down into their constituent

parts. According to CHF historians, alchemists hoped this substance could be used to make the fabled phi-losophers’ stone, which would in turn make gold from cheaper metals. While making his copy of the text, New-ton inserted comments, explanations, and corrections, demonstrating a serious study of the alchemical work.

The paper’s translated title is “Prepa-ration of the [Sophic] Mercury for the [Philosophers’] Stone by the Antimonial Stellate Regulus of Mars and Luna from the Manuscripts of the American Philosopher.” Though CHF does not currently have plans to display the manuscript, it will be available for scholarly research and it will

be digitally added to Indiana University’s (IU) “The Chymistry of Isaac Newton” project.

Though mostly known for his development of physics and calculus, “Newton wrote and transcribed about a million words on the subject of alchemy,” notes the IU project’s website. “Newton’s alchemical manuscripts include a rich and diverse set of docu-ment types, including laboratory notebooks, indices of alchemical substances, and Newton’s transcriptions from other sources.”

Bottling that old book smell

Old books like the Newton manuscript help tell the story of chemistry. In return, chemistry can tell us a lot about old books. Analysis of the lignin and cellulose content

of the paper can hint at the vintage and manufacturing methods of an antique tome, as can a careful chemical look at the cover and binding.

A lot of research has been carried out on the chemistry of old books so that libraries can develop the chemical tools they need to preserve aging print resources. Erin Elizabeth Long is one of a handful of entrepreneurs using that research to bring the scent of the rare books department home, with her Secondhand Bookstore scent.

Long found consensus in the literature that the break-down of lignin in wood-based paper produces vanillin,

also known as vanil-la flavor. In addition to that, she says, “as the lignin and cel-lulose break down, you start to get aromatic hydrocar-bons and aldehydes like benzaldehyde, toluene, and ethyl-benzene, which are described as hav-ing almondlike or slightly sweet floral odors in the small quantities found in old books.”

Her complex scent also includes notes of oak, mahogany, tobacco,

and sweetgrass to capture the woody notes, and leather to bring in the binding. Finally, she adds “musk to rep-licate the slightly musty, dusty scent of old books and a hint of black tea for an acrid note that reminded me of the scent of ink.”

Secondhand Bookstore is available at the Etsy shop GeekMarket in a roll-on fragrance. The hand-made craft website also has several old-book-scented candles to choose from, perfect for an evening of bibliophile romance.

Whiff: The smell of old books is available in fragrances and candles.

With the ACS Manuscript Transfer Service, editors can now review

a paper and suggest the transfer of a submission to another

ACS journal. The beneft to you, the author? You have another

opportunity to see your research published in an ACS journal

without having to restart the entire submission process.

LEARN MORE AT

pubs.acs.org/transfer

Reques

Spectrum Chemicals are Now Available

in Europe from VWR International

E U R O P E

Come Visit Us June 1 - 2, 2016 at

Messe Basel, Switzerland - Booth #E84