Article Little Green Molecules

8/12/2019 Article Little Green Molecules

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82 SCIENTIFIC AMERICAN MARCH 200

Little Green

MoleculesBy Terrence J. Collins and Chip Walter

POLLUTION CONTROL:Catalysts calledTAMLs ( green ) work with hydrogen peroxide(blue) to break down chlorophenols (brown),which contaminate the wastewater frommany industrial sources.

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www.sc iam.com SCIENTIFIC AMERICAN 83

CREDT

Chemists have invented a new class of catalysts that can destroysome of the worst pollutants before they get into the environment



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2005 Shanna H. Swan of the Universityof Rochester School of Medicine andDentistry reported similar effects inmale infants. Another study headed bySwan found that men with low spermcounts living in a rural farming area ofMissouri had elevated levels of herbi-cides (such as alachlor and atrazine) intheir urine. Starting from our factories,farms and sewers, persistent pollutantscan journey intact by air, water and upthe food chain, often right back to us.

To confront this challenge, greenchemists at universities and companiesare investigating the feasibility of replac-ing some of the most toxic products andmanufacturing processes with more en-vironment-friendly alternatives [ see boxon page 88 ]. The work of Collinss teamat Carnegie Mellon traces its originsback to the 1980s, when public healthconcerns about chlorine were intensify-ing. Chlorine was then, and still is, oftenused for large-scale cleaning and disin-

fection in manufacturing, as well as forthe treatment of drinking water. Al-though chlorine treatment is inexpensiveand effective, it can create some ugly pol-lutants. The bleaching of wood pulp withelemental chlorine in paper mills hadbeen a major source of cancer-causingdioxins until the Environmental Protec-tion Agency banned the process in 2001.(Most mills now bleach wood pulp withchlorine dioxide, which reduces the pro-duction of dioxins but does not eliminateit.) By-products created by the chlorina-tion of drinking water have also beenlinked to certain cancers. Chlorine in itscommon natural form chloride ions orsalts dissolved in water is not toxic, butwhen elemental chlorine reacts with oth-er molecules it can generate compoundsthat can warp the biochemistry of livinganimals. Dioxins, for instance, disruptcellular development by interfering witha receptor system that regulates the pro-duction of critical proteins.

Rather than relying on chlorine, wewondered if we could put natures owncleansing agents hydrogen peroxideand oxygen to the work of purifyingwater and reducing industrial waste.These cleansers can safely and power-fully obliterate many pollutants, but innature the process usually requires anenzyme a biochemical catalyst thatvastly increases the rate of the reaction.Whether natural or man-made, catalystsact as old-fashioned matchmakers, ex-cept that rather than bringing two peo-ple together they unite specific mole-cules, enabling and accelerating thechemistry among them. Some naturalcatalysts can boost chemical reactionrates a billionfold. If not for an enzymecalled ptyalin, found in our saliva, itwould take several weeks for our bodiesto break down pasta into its constituentsugars. Without enzymes, biochemistrywould move at a numbingly slow pace,and life as we know it would not exist.

WATER POLLUTIONcomes from many sources, but the newly invented TAML catalysts may beable to destroy some of the worst contaminants before they enter rivers and lakes. For

example, applying TAMLs to the wastewater from textile and pulp mills could break down dyes,organochlorines and other hazardous chemicals. TAMLs could also be used to treat the runoff from

agricultural waste lagoons as well as residential sewage, which contains dyes from washingmachines and traces of harmful pharmaceuticals that are excreted in human urine.

TEXTILE MILLDyes

PULP MILLColored lignin fragments,organochlorines

FARMHerbicides,

insecticides,animal waste

and medicines

SEWERDyes,cosmetics,drugs

DONFOLEY



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In nature, enzymes called peroxidas-es catalyze reactions involving hydrogenperoxide, the familiar household chemi-cal used to bleach hair and remove car-pet stains. In forests, fungi on rottingtrees use peroxidases to marshal hydro-

gen peroxide to break down the ligninpolymers in the wood, splitting the largemolecules into smaller ones that the fun-gi can eat. Another family of enzymes,the cytochrome p450s, catalyzes reac-tions involving oxygen (also called oxi-

dation reactions). Cytochrome p450s in

our livers, for example, use oxygen toefciently destroy many toxic moleculeswe inhale or ingest.

For decades, chemists have beenstruggling to build small synthetic mol-ecules that could emulate these enor-mous enzymes. If scientists could createdesigner molecules with such strong cat-alytic abilities, they could replace thechlorine- and metal-based oxidationtechnologies that produce so many pol-lutants. In the early 1980s, however, noone was having much luck developingtest-tube versions of the enzymes. Overbillions of years of evolution, nature hadchoreographed some wonderfully ele-gant and extremely complex catalyticdances, making our efforts in the labo-ratory look clunky. Yet we knew that wecould not achieve our goal of reducingpollution unless we found a way to mim-ic this molecular dance.

Catalytic Convertersc r e a t i n g s y n t h e t i c enzymes alsomeant assembling molecules that wouldbe robust enough to resist the destructivereactions they were catalyzing. Anychemistry involving oxygen can be de-

structive because the bonds it makeswith other elements (especially hydrogen)are so strong. And because each mole-cule of hydrogen peroxide (H 2O2) is half-way between water (H 2O) and molecu-lar oxygen (O 2), this compound is also

strongly oxidizing. In water, hydrogenperoxide often produces a kind of liquidre that demolishes the organic (carbon-containing) molecules around it. A les-son from the enzymes was that a work-ing catalyst would probably need to have

an iron atom placed inside a molecular

matrix of organic groups. So we had totoughen the molecular architecture ofsuch groups to ensure they could survivethe liquid re that would result from theactivation of hydrogen peroxide.

Borrowing further from natures de-sign, we eventually solved this problemby creating a catalyst in which four ni-trogen atoms are placed in a square witha single iron atom anchored in the mid-dle [see box on opposite page ]. The ni-trogen atoms are connected to the muchlarger iron atom by covalent bonds,meaning that they share pairs of elec-trons; in this kind of structure, thesmaller atoms and attached groups sur-rounding the central metal atom arecalled ligands. Next we linked the li-gands to form a big outer ring called amacrocycle. Over time we learned howto make the ligands and linking systemstough enough to endure the violent reac-tions that the TAMLs trigger. In effect,the ligands we invented became a kindof rewall that resisted the liquid re.The longer it resisted, the more usefulthe catalyst. Of course, we did not wantto create an indestructible catalyst,which could end up in efuent streams

and perhaps produce a pollution prob-lem of its own. All our existing Fe-TAMLcatalysts (TAMLs with iron as the cen-tral metal atom) decompose on time-scales ranging from minutes to hours.

Building the ligand rewalls was not

easy. It required developing a painstak-ing four-step design process in which werst imagined and then synthesized li-gand constructions that we hoped wouldkeep the rewall in place. Second, wesubjected the catalyst to oxidative stress

until the rewall dis-integrated. Third, welooked for the preciselocation where thebreakdown began.

(We found that ligand degradations al-

ways start at the most vulnerable site.)And in the nal step, once we had pin-pointed the weakest link, we replaced itwith groups of atoms we believed wouldhold up longer. Then we started thewhole design cycle again.

After 15 years, we nally created ourrst working TAML. We knew we hadsucceeded one morning when ColinHorwitz, a research professor at our in-stitute, showed off the results of ableaching experiment that featured ourmost advanced design at the time. Welooked at the results, and there it was:every time Horwitz squir ted dark dyeinto a solution containing the TAMLcatalyst and hydrogen peroxide, the so-lution quickly turned colorless. We nowknew that our firewalls were finallyholding up long enough to allow theTAMLs to do their job. The moleculeswere acting like enzymes, and yet theywere much, much smaller: the molecularweight of a TAML is about 500 daltons(a dalton is equal to one twelfth the massof carbon 12, the most abundant isotopeof carbon), whereas the weight of horse-radish peroxidase, a relatively small en-zyme, is about 40,000 daltons. The di-minutive TAML activators are easierand cheaper to make, and much moreversatile in their reactivity, than theirnatural counterparts.

Since then, we have evolved morethan 20 different TAML activators byreapplying the same four-step designprocess that enabled us to create the rst

TERRENCE J. COLLINSand CHIP WALTERhave worked together to educate the public aboutthe challenges and possibilities of green chemistry. Collins is Thomas Lord Professor ofChemistry at Carnegie Mellon University, where he directs the Institute for Green Oxida-tion Chemistry. He is also an honorary professor at the University o f Auckland in NewZealand. Walter is a science journalist and author of Space Age and Im Working on That(with William Shatner). He teaches science writing at Carnegie Mellon and is a vice pres-ident of communications at the University of Pittsburgh Medical Center.

T H E

A U T H O R S

Whether natural or man-made, catalysts act as

old-fashioned matchmakers.



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A MOLECULAR CLEANING MACHINEChemists designed TAMLs to emulate the natural enzymes that catalyze reactions involving hydrogen peroxide. TAMLs, though,are hundreds of times smaller than enzymes, so they are easier and cheaper to manufacture.

TAML

At the center of each TAML isan iron atom bonded to fournitrogen atoms; at the edgeare carbon rings linked to forma big outer ring called amacrocycle. This linkingsystem acts as a rewall,enabling the molecule toendure the violent reactions ittriggers. In its solid s tate theTAML also has one watermolecule (H2O) attached tothe iron atom. (The attachedgroups are called ligands.)

When a TAML dissolves in water, another molecule of H2O connects tothe catalyst ( a). If hydrogen peroxide (H2O2) is also in the solution, itcan replace one of the water ligands, which are loosely attached andeasily expelled (b). The peroxide ligand then discards bo th its

hydrogen atoms and one oxygen atom in the form of a watermolecule, leaving one oxygen atom attached to the iron (c). Theoxygen pulls electrons far ther away from the iron atom, turning theTAML into a reactive intermediate.

When in solution with molecules of pentachlorophenola toxic chemical used inwood treatmentTAMLs and hydrogen peroxide break down the pollutant tonontoxic compounds and ions. The strong positive charge of the iron atom in thereactive intermediate enables the molecule to destroy pollutants, althoughscientists have not yet de termined the details of the process.

Macrocycle

Hydrogenperoxide

Waterligand

Peroxideligand

Expelled watermolecule

Carbondioxide

Anotherexpelled watermolecule

Pentachlorophenol

Waterligand

Waterligand

a b c

KEY

MELSSATHOMAS

SOURCE

ARAN

CHANDAInstituteforGreenOxidationChemistry

+++

+ ++

Iron

NitrogenOxygenCarbonChlorineHydrogen

Oxalic acid

Chlorideions



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working model. Each TAML has its ownreaction rate and lifetime, allowing us totailor the catalysts to match the tasks wewant them to perform. Most of the cata-lysts incorporate elements such as car-bon, hydrogen, oxygen, nitrogen andiron, all chosen for their low toxicity.We call some of the molecules hunterTAMLs because they are designed toseek out and lock onto specic pollut-ants or pathogens, in much the sameway that a magnetized mine seeks outthe metal hull of a ship. Other TAMLsact as blowtorches that aggressivelyburn most of the oxidizable chemicalswith which they come into contact. Stillothers are less aggressive and more selec-tive, so that they will, for example, at-tack only certain parts of molecules orattack only the more easily oxidizedmolecules in a group. We expect to adaptTAMLs to advance green chemistry fordecades to come. Although more toxic-ity testing must be done, the results so

far indicate that TAMLs break downpollutants to their nontoxic constituents,leaving no detectable contamination be-hind. We now have more than 90 inter-national patents on TAML activators,with more in the pipeline, and we alsohave several commercial licenses.

Interestingly, we still do not know allthe details of how the TAMLs work, butrecent studies have provided deep in-sights into the key reactions. In their sol-id state, Fe-TAMLs generally have onewater molecule attached as a ligand tothe iron atom, oriented perpendicularlyfrom the four nitrogen ligands; when putin solution, another water molecule con-nects to the opposite side of the ironatom. These water ligands are very loose-ly attached if hydrogen peroxide is alsoin the solution, a molecule of it easily re-places one of the water molecules. Theperoxide ligand swiftly reconstitutes it-self, expelling both its hydrogen atomsand one oxygen atom (which escape as

H 2O, a water molecule) and leaving oneoxygen atom attached to the iron at thecenter of the Fe-TAML, which is nowcalled the reactive intermediate (RI).

Oxygen is much more electronega-tive than iron, which means that its nu-cleus pulls most of the electrons in thecomplex bond toward itself and awayfrom the iron nucleus. This effect in-creases the positive charge of the iron atthe center of the TAML, making the RIreactive enough to extract electronsfrom oxidizable molecules in the solu-tion. We have not yet determined howthe RI breaks the chemical bonds of itstargets, but current investigations maysoon reveal the answer. We do know,however, that we can adjust the strengthof the TAMLs by changing the atoms atthe head and tail of the molecule; put-ting highly electronegative elements atthose locations draws even more nega-tive charge away from the iron andmakes the RI more aggressive.

CHEMISTRY GOES GREENThe invention of TAML catalysts is just one of the many achievements of green chemistry, which strives to develop products andprocesses that reduce or eliminate the use and generation of hazardous substances. Some other accomplishments are listed below.

PROJECT PARTICIPANTS STATUS

Using plant sugars to cr eate polylactic acids(PLAs), a family of biodegradable polymersthat could replace many traditional petroleum-derived plastics

Patrick Gruber, Randy L. Howard,Jeffrey J. Kolstad, Chris M.Ryan and Richard C. Bopp,NatureWorks LLC(a subsidiary of Cargill)

NatureWorks has built afactory in Nebraska tomanufacture PLA pellets,which are used to makewater bottles, packagingmaterials and otherproducts

Discovering synthesis reactions that allowmanufacturers to substitute water for manycommon organic solvents, some of whichcan cause cancer

Chao-Jun Li, McGill University Pharmaceutical and commodity chemical companiesare investigating the process

Developing metathesis chemistry, a method oforganic synthesis that can produce drugs,plastics and other chemicals more e fficientlyand with less waste

Robert H. Grubbs, CaliforniaInstitute of Technology;Richard R. Schrock,Massachusetts Institute ofTechnology; Yves Chauvin,French Petroleum Institute

Widely applied in thechemical, biotechnologyand food industries,this research was awardedthe 2005 Nobel Prizein Chemistry

Replacing toxic petroleum-based solvents withsupercritical carbon dioxide, a high-temperature, high-pressure fluid that has theproperties of bo th a liquid and a gas

Martyn Poliakoff, MichaelGeorge and Steve Howdle,University of Not tingham,England

Thomas Swan & Co., a British manufacturer of spec ialtychemicals, has built a plant that uses supercr itical fluids

Inventing a new method for producingsertraline, the key ingredient in theantidepressant Zoloft

James Spavins, Geraldine Taber,Juan Colberg and DavidPfisterer, Pfizer

The process has reduced pollution, energy and water usewhile improving worker safety and produc t yield



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Industrial Strengthb u i l d i n g t a m l s in the laboratory isone thing; scaling them up for commer-cial use is another. So far the lab tests andeld trials have been promising. Testsfunded by the National Science Founda-

tion, for example, demonstrated that Fe-TAMLs plus peroxides could clean upthe contamination from a bioterror at-tack. We found that when we combinedone TAML with tertiary butyl hydroper-oxide a variation of hydrogen peroxidethat replaces one of the hydrogen atomswith a carbon atom and three methyl(CH 3) groups the resulting solutioncould deactivate 99.99999 percent of thespores of Bacillus atrophaeus, a bacte-rial species very similar

to anthrax, in 15 min-utes. In another impor-tant potential applica-tion, we hope to use Fe-TAMLs and hydrogenperoxide to someday create an inexpen-sive disinfectant to tackle the infectiouswaterborne microbes that account for somuch death and disease worldwide.

In three eld trials, we explored howwell TAMLs can alleviate the pollutioncreated when paper is manufactured.Every year the paper and wood pulp in-dustry produces more than 100 millionmetric tons of bleached pulp, which isturned into white paper. Besides gener-ating dioxins, chlorophenols and otherhazardous organochlorines, many pulpmills discharge a coffee-colored efuentthat stains streams and rivers and blockslight from penetrating the water. The re-duction of light interferes with photo-synthesis, which in turn affects organ-isms that depend on plants for food. Thesources of the staining are large coloredfragments of lignin, the polymer thatbinds the cellulose fibers in wood.Bleaching with chlorine dioxide removesthe lignin from the cellulose; the smallerlignin fragments are digested by bacteriaand other organisms in treatment pools,but the larger pieces are too big to beeaten, so they end up in rivers and lakes.

We have tested the effectiveness of Fe-TAMLs at decolorizing these fragmentsat two pulp mills in the U.S. and one inNew Zealand. In New Zealand we com-

bined Fe-TAMLs and peroxide with50,000 liters of efuent water. In the U.S.we directly injected Fe-TAMLs into apulp-treatment tower or an exit pipeover the course of several days to bleachthe wastewater. Overall, the Fe-TAMLs

reduced the staining of the water by upto 78 percent and eliminated 29 percentof the organochlorines.

The development of other TAML ap-plications also looks exciting. Eric Gei-ger of Urethane Soy Systems, a companybased in Volga, S.D., has found that Fe-TAMLs do an excellent job processingsoybean oil into useful polymers thatdisplay physical properties equal to, ifnot better than, those of current poly-

urethane products. TAMLs may evennd their way into washing machines: inanother series of tests, we found that atiny quantity of catalyst in certain house-hold laundry products eliminated theneed to separate white and colored cloth-ing. TAMLs can prevent staining by at-tacking dyes after they detach from onefabric but before they attach to another.We are also working on a new family ofTAMLs that can break the very stablemolecular bonds that allow drugs andagricultural chemicals to pass intact intodrinking water.

Despite the success of these trials, wehave not resolved all the questions aboutTAML activators. More testing on in-dustrial scales remains to be done, andit is important to ensure that TAMLs donot create some form of pollution wehave not yet observed. Too often chemi-cal technologies have seemed completelybenign when rst commercialized, and

the devastating negative consequencesdid not become clear until decades later.We want to do everything in our powerto avoid such surprises with TAMLs.

Cost is also an issue. AlthoughTAMLs promise to be competitive in

most applications, large corporations aredeeply invested in the chemical processesthey currently use. Shifting to new sys-tems and techniques, even if they work,usually requires signicant investments.One great advantage of TAML technol-ogy, though, is that it does not requiremajor retooling. What is more, TAMLsmay ultimately save companies moneyby offering a cost-effective way to meetincreasingly stringent environmental

laws in the U.S., Europe and elsewhere.The advances of green chemistry to

date represent only a few interim stepson the road to dealing with the many en-vironmental challenges of the 21st cen-tury. The deeper question is, Are we go-ing to practice acute care or preventivemedicine? Right now most chemists arestill trained to create elegantly structuredcompounds that solve the specic prob-lem for which they have been engineered,without regard to their broader impact.We are in effect performing global-scaleexperiments on our ecosystems and our-selves, and when these experiments failthe cost can be catastrophic. New greenchemical techniques offer an alternative.The Industrial Revolution has unfolded,for the most part, without design or fore-thought. Perhaps now we can take somecreative steps to reverse that trend andhelp make a world, and a future, that wecan live with.

M O R E T O E X P L O R E Toward Sustainable Chemistry.Terrence J. Collins in Science, Vol. 291, No. 5501, pages 4849;January 5, 2001.Rapid Total Destruction of Chlorophenols by Activated Hydrogen Peroxide.Sayam Sen Gupta,Matthew Stadler, Chris topher A. Noser, Anindya Ghosh , Bradley Steinhoff, Dieter Lenoir, Colin P.Horwitz, Karl-Werner Schramm and Terrence J. Collins in Science, Vol. 296, pages 326328;April 12, 2002.More information can be found online atwww.cmu.edu/greenchemistryand www.chemistry.org/portal/a/c/s/1/acsdisplay.html?DOC=greenchemistryinstitute\index.html

Building TAMLs in the laboratory is one thing;scaling them up for commercial use is another.

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