As was cited in the Angewandte report, Derek Lowe noted that this kind of thing has happened before in the field of catalysis. It’s worth briefly recounting the story of one of those historical cases.

Organic chemists rely on metals to make many different chemical bonds, including carbon-carbon, carbon-nitrogen, and carbon-oxygen bonds. But this particular tale dates to a time when many of the most famous metal-catalyzed reactions used today were just hitting their stride.

In 1983, Tamejiro Hiyama, Hitosi Nozaki, and coworkers at Kyoto University in Japan reported a new chromium-mediated reaction for forming carbon-carbon bonds. Because the reaction could selectively form particular types of structures, and it could be run without disturbing potentially sensitive parts of molecules, the reaction caught the eye of several of the research groups working on making highly complex structures, including that of Yoshito Kishi at Harvard University.

At the time, Kishi’s team was trying to make a monster of a molecule from scratch. The target was palytoxin, a dauntingly complex molecule first isolated from a coral reef animal, and one of the most poisonous small molecules known to man. At the time, it was the most poisonous substance known, with the exception of some proteins from bacteria and plants. Why make such a molecule at all? Well, part of it’s the challenge of the journey, the realization that making such a tough molecule will push your chemistry toolkit to the limit and force you to innovate, to invent new reactions or improve old ones. (The latter is what happened here).

The Kishi team had a tough carbon-carbon bond to make en route to palytoxin, and most of the tools in their toolkit weren’t cutting it. So they turned to Nozaki’s chromium-mediated method, which, after some adjustments, turned out to be successful.

As an aside, I should mention that chromium salts are very toxic. But I suppose if you’re trying to make something as dangerous as palytoxin, using chromium salts in the synthesis is the least of your problems. My cursory web searches suggest it takes only micrograms of palytoxin to kill a person- it’s a potent neurotoxin. Anecdotally, folks making palytoxin had to wear hazmat suits once they got past a certain point in the synthesis. That makes sense to me, given the experimentals (the team made about a milligram of palytoxin and several milligrams of closely related compounds). I haven’t been able to verify this in the papers, though.

But there’s more to the story. From the original report:

The Cr(II)-mediated coupling reaction provided an excellent solution to our problem except one technical difficulty we had yet to overcome….the success of this coupling mysteriously depended on the source and batch of CrCl₂. We also tested the homemade Cr(II) reagent without success. These facts naturally suggested an intriguing possibility that the success of this reaction might depend on some unknown contaminant in CrCl₂.

Imagine the situation- the reaction worked better, worse, or not at all, depending on which company the chromium reagent came from, or the particular lot number on the bottle. So Kishi’s group tested the several metal salts to see whether anything affected the reaction. Sure enough, nickel(II) chloride had a beneficial effect when combined with CrCl₂. Nozaki and colleague Kazuhiko Takai independently uncovered the same thing. The teams’ 1986 reports appear in the same journal, within 500 pages of each other. Today, the reaction is known as the Nozaki-Hiyami-Kishi coupling reaction.

It was a nifty find, but what elevates these papers beyond niftiness is that the discovery transformed a somewhat erratic reaction into a reliable one that chemists have since harnessed for building many molecules.

Kishi’s group went on to use this reaction in a key step on their odyssey to palytoxin, which they completed in 1994. The sheer size and complexity of palytoxin renders the work a major achievement for organic chemists.

It’s important to remember that contaminants happen outside of organic chemistry, too. And the contaminants aren’t always doing beneficial things. Take, for example, a recent report in Science, which notes that additives used to make disposable plastic labware, such as pipette tips, can leach and interfere with biological assays. It’s something to keep in mind, no matter what kind of labwork you’re doing.

More reading:
Angew. Chem. Int. Ed., DOI: 10.1002/anie.200902237
Classics in Total Synthesis, Chapter 36
Tet. Lett. 1983, 24, 5281
J. Am. Chem. Soc. 1986, 108, 5644.
J. Am. Chem. Soc. 1986, 108, 6048.
J. Am. Chem. Soc. 1989, 111, 7525 and 7530.
J. Am. Chem. Soc. 1994, 116, 11205.
Science 2008, 322, 917.

Images: Albert Kok (Wikimedia Commons); J. Am. Chem. Soc. 1994

One of the ACS initiatives is an effort to have the U.S. Postal Service adopt chemistry as a theme for a commemorative stamp in 2011. Since USPS gets about 50,000 subject requests per year and awards only 25 commemorative stamps per year, your efforts are needed to advance this cause. More on that in a moment.

Activities planned during IYC 2011 will accomplish the following:

• Increase the public appreciation of chemistry in meeting world needs
• Increase the interest of young people in chemistry
• Generate enthusiasm for the creative future of chemistry
• Celebrate the 100th anniversary of the Mme. Curie Nobel Prize in Chemistry and the 100th anniversary of the founding of the International Association of Chemical Societies (the predecessor to IUPAC).

As Judith L. Benham, chair of the ACS Board of Directors, wrote in a letter to ACS committee chairs earlier this year: “The principal goal of IYC is to celebrate the achievements of chemistry and its contributions to the well-being of humankind. We are pleased that this goal dovetails with the ACS vision and mission and several of ACS’s top strategic goals: to create and sustain global scientific community; to address global challenges through chemistry; and to communicate the nature and value of chemistry and related sciences.”

The UN celebrated 2005 as the International Year of Physics. This year, 2009, is the UN’s International Year of Astronomy. For some weird reason, the U.S. government has a policy against supporting International Year designations, so if our country is going to have a significant presence during IYC 2011, it’s going to be up to ACS to take the lead.

We have formed a staff task force, on which I sit as C&EN’s representative, to help focus our efforts. We have some time to decide on and prepare for events in 2011. It seems likely that already planned events such as Chemists Celebrate Earth Day and National Chemistry Week will have an IYC 2011 flavor to them.

We don’t have as much time for the commemorative stamp effort. We would like the Citizen’s Stamp Advisory Committee to act this year in recommending a chemistry commemorative stamp for 2011. One powerful tool we have is a petition signed by tens of thousands of Americans requesting such a commemorative stamp.

In this week’s print edition is just such a petition, ready for you to remove from C&EN and circulate widely. It doesn’t have to be signed just by chemists. You can take it to work, circulate it in your neighborhood, and have family and friends sign it. If you do not want to tear it out of C&EN, you can download a PDF file.

As soon as possible, but no later than Nov. 1, 2009, please mail the completed petitions to ACS Celebrates IYC 2011, c/o American Chemical Society, Office of International Activities, 1155—16th St., N.W., Washington, DC 20036, or fax them to (202) 872-6317. For more information on ACS activities related to IYC 2011, please visit www.acs.org/iyc2011.

Thanks for reading. And thanks for signing!

Today, we all nearly expired sitting out in the noon sun for nearly two hours, listening to the Lindau conference’s panel about climate change and sustainability, which featured some of the usual suspects in these debates (such as the IPCC’s Rajendra Pachauri and the controversial writer Bjørn Lomborg). Also present: other Nobel Laureates (Molina, Schrock), climate scientist Thomas Stocker and a rep from the German government, lover of solar technology. The Economist’s science editor Geoff Carr moderated.

The sweltering discussion took place on an island called Mainau. (It’s got a castle. Stay tuned for photos of the strange bullet-like ferry we took from Lindau to Mainau, and the boat’s decorative balloon molecules.)

So panel members mostly stuck to their typical mantras: Pachauri: the world is growing unsustainably and we need to do something about climate change. Lomborg: climate change is an issue, but we have other more pressing world problems than climate change to solve, such as world health. Molina: The planet is facing irreversible threats; we have to invest in new renewable energy technologies and cut consumption. Cornelia Quennet-Thielen (from the German Ministry for Education and Science): One million new jobs in the solar energy sectors means renewable energy can help the economy. Schrock: There are many renewable energy problems that chemistry can solve.

To be honest, I was mostly interested in finding out what the delegates would say about the upcoming United Nations conference in Copenhagen this December, which will aim to develop a workable global agreement to fight climate change… since the Kyoto Protocol has not been what one might call a stellar success. Lomborg played pessimist, “We will get together in Copenhagen and make promises, but will we keep them?,” while Pachauri was excessively optimistic. He said an agreement in Copenhagen would be found and enforced, arguing that public awareness was “light years” ahead of where it was during the Kyoto negotiations. “The world has changed,” Pachauri said, adding that this public awareness means governments would get voted out if they don’t ratify or enforce whatever comes of Copenhagen. He mentioned this increase of awareness is a key to changing our consumptive lifestyle. I’m really not convinced about the last point, and it’s one I’ve heard before on such panels.

Although I am choosing to be optimistic about Copenhagen, and I’m even willing to hope that this increasing awareness about climate science may inspire the public to vote in sustainably-bent politicians. But knowledge doesn’t change human behavior, when we humans enjoy doing what we are doing.

Consider personal health, a subject arguably closer to the human heart than the environment. Nutritionists have been telling us for years that eating right and exercising makes for a longer life. I’d wager that more people believe that the nutritionists are correct about eating right than they believe scientists about climate change. But being educated sure hasn’t stopped the obesity epidemic. We love our twinkies and we love our cars, and left to our own devices we’d probably not curb our enjoyment of either, or at least not enough to stop both impending catastrophes. Education is not superfluous, but what we need are good polices, and ones that are enforced.

Incidentally, both the panel moderator Carr and nobelist Roger Tsien, who was sitting in the audience, asked the panelists to point out specific renewable energy needs, since there were hundreds of budding young scientists in the audience who might put their brains to the problem(s). But the only person to list off specifics was Pachauri, who called for the development of small turbines to use as biomass gasifiers. He also asked for a way to convert agricultural cellulose waste into usable fuels. Everyone else ducked the question by saying that basic research was important. (Sure it is, but that wasn’t the answer to the question!)

Afterwards, lots of people were talking about Tsien’s “on-stage self-psychoanalysis,” as one guy from Germany put it. Tsien gave a down-to-earth synopsis of his search for a scientific research area that would “suit my neuroses” and encouraged delegates to do the same. Some of Tsien’s mental health considerations: He feels really uncomfortable with competition. He’s the youngest of three brothers and according to sibling psychology prefers to eke out his own niche. Then there’s his penchant for bright colors. And finally, he feels that biology offers the “most interesting grand questions in all of science currently doable by individuals.” (Big physics questions relying on expensive gadgets that you have to share among lots of people.) So deciding to apply his chemistry know-how to biology, he went looking for his own niche relatively free of competition, with, uh, obviously good results.

Anyway, besides the self-psychoanalysis, Tsien also hasn’t hesitated to get political. At a press conference Wednesday, a Chinese journalist asked him what sort of advice he would give to help young Chinese people become successful. Tsien first noted that Chinese people are hard workers and have made important discoveries. “The problem right now,” he said, “is intellectual freedom.” Tsien added that it’s important that young people have the freedom to challenge what “big shot professors or politicians tell them.”

In addition to an eclectic assortment of international media, there are also some celebrity bloggers here, such as Coturnix and PZ Myers. Royalty has also made a cameo: Thai Princess Maha Chakri Sirindhorn showed up for a couple of days. (Sirindhorn should not be confused with her sister Princess Chulabhorn, who has a PhD in chemistry and her own research institute.)

Gerhard Ertl chats with a delegate

I’m on a seriously quaint but very humid island called Lindau in Germany’s Lake Constance this week, surrounded by more than 20 Nobel laureates, and nearly 600 young researchers who are lucky (and smart) enough to have nabbed a chance to mingle with these science celebrities. No advisors at the Lindau conference, just students and postdocs from 67 countries, from as far afield as Chile or Pakistan. (Harry Kroto told me he feels like the equivalent of a scientific rock star here…)

Besides talks and panel discussions by the laureates, students get to chitchat with their heroes in small groups. A Swedish count started the Lindau meetings in 1951 and each year the conference focus toggles through the different prize themes—last year the focus was on physics, this year it’s chemistry. His daughter Countess Bettina runs the show now, sporting a fetching hat.

The mood here has been super congenial—I ran across Bob Grubbs drawing structures on a notepad with a pair of delegates. But the weather has been ridiculously humid, with most delegates looking as cheery as they are moist. Somehow Poornima Rangadurai, a chemistry undergraduate from Chennai, India, managed to overcome the heat when she gave a super cool traditional Indian song and dance performance Monday evening.

But every morning, laureates speak about whatever their heart desires. Many have stuck to topics close to their prize-winning research—for example Gerhard Ertl spoke about surface science, Sherwood Rowland about greenhouse gases, Ryoji Noyori about synthesizing drugs.

Others have strayed from science during their presentations. For example, Richard Ernst spoke primarily about his passion for Buddhist Tibetan art, making only a few, brief references to NMR–“my little toy”—whose development won him the Nobel Prize. Ernst used his time on stage to tell delegates to diversify their interests, so as not to become “one-sided nerds.” He also mentioned a cool project that teaches science to Tibetan monks, and also the conservation chemistry he does in his home lab.

Today, Walter Kohn chose to show a movie about solar energy that he helped produce, which is strangely but wonderfully narrated by Monty Python star John Cleese. (Cleese has a perfectly authoritative voice, but as the guy next to me commented, during the serious documentary, “you’re always waiting for him to give the punch line.”) Kroto also only briefly mentioned buckyballs, amidst his energetic talk that touched upon everything from atheism, his web 2.0 projects and his love of design.

Besides chemistry, this year’s conference also has renewable energy and global sustainability as themes, and keeping with that, Peter Agre, spent his slot on stage giving a gorgeous slide show of several canoe trips he’s made with family and friends in the Arctic, “images of what we are losing as the current energy consumption patterns continue.”

As you might be able to guess from Algenol’s name, the idea is to use specially-engineered algae to make the ethanol, which would be used as fuel or as a feedstock for plastics.

Both of the stories are business stories, so I don’t expect them to have a great deal of information about the science behind this announcement. But it’s important to emphasize a potential stumbling block for this technology-getting the ethanol the algae makes into a usable form.

The Times’s online edition mentioned that concern briefly in their story, while Green Inc. doesn’t mention it.

From the Times story:
Among the steps still being improved is the separation of the oxygen and water from the ethanol. The Georgia Institute of Technology will work on that process, as will Membrane Technology and Research, a company in Menlo Park, Calif.

It takes plenty of energy to distill ethanol- I’m not clear on where Dow/Algenol are going to obtain the heat to do the distillation, and how that fits into the overall carbon dioxide balance for their process. Membrane Technology and Research, one of the partners mentioned in the Times article, is working on ways to save energy during the distillation step. That link provides a little more detail about their energy-saving process, which combines distillation and permeable membranes.

I wish Dow, Algenol, and partners the best in getting U.S. Department of Energy grant they’re after. We’ll never know if this or any alternative fuel-making process is feasible on a practical scale unless someone ponies up for the tinkering and testing phase.

Image: Shutterstock

1. A musical interlude.

There was a serious jam session/sing-a-long last night in the overflow dining tent. I hear it’s a standing gig, and if you don’t know how to play an instrument, you’re encouraged to pick one up and learn. There were some usual suspects—guitar, banjo, harmonica, violin—and some less expected additions—a full drum kit, mandolin, and a saw. Earlier in the day, I had noticed some mysterious markings on the floor of the tent. Turns out, they are song chords. Crowd favorites? Dylan (“Don’t Think Twice, It’s Alright”), Talking Heads (“Psycho Killer”), and Beatles (“Hide Your Love Away”).

2. Mosquitos.

Before I left for Alaska, I told friends I needed to track down Deet and a mosquito net. Many were perplexed: there are mosquitos in the arctic? Sure are. Each person has their own personal swarm. It reminds me of the dirt cloud perpetually surrounding Pigpen. Breck Bowden, a scientist who has been coming up here for two decades, commented at breakfast yesterday that the mosquitos this summer are the worst he’s seen since 1997. Constant itching isn’t the only problem; the pests can get into instrumentation in the field and seriously throw off measurements. We witnessed their meddling ways when we went out to measure carbon exchange in a particularly mosquito-rich area of heath. For a small taste of what it’s like, another reporter on the trip posted video of what happens when you put nine journalists in a bug-filled van.

3. Guacamole.

The food here is amazing. This isn’t your typical cafeteria food. I’m told because it costs so much to get food up here (we’re a 12-hour drive from Fairbanks) that it doesn’t make that much of a difference to get the good stuff. So far we’ve had Mexican, Indian, fresh fish, and many other tasty treats. From the looks of the menu, there’s a Thanksgiving dinner coming our way on Sunday. It’s strictly BYOB (for some crazy reason, NSF won’t pay for Alaskan IPA), and researchers clearly have carefully planned their summer drinking plan.

4. Five kinds of paella.

As part of that really amazing food, the kitchen staff works overtime to accommodate everyone’s dietary needs or choices. On paella night, there was regular paella (meat and fish), vegetarian paella (fish and veggie sausage), vegan paella (veggie sausage only), no-seafood paella, and Cody’s paella (a special treat for the one gluten-free researcher on camp).

5. A mini laundromat.

Because it is 75 cents a gallon to pump water out and haul it to Prudhoe Bay, laundry ends up costing the camp $22.50 per load. Understandably, each visitor is only allowed one washing every two weeks, and sharing loads is encouraged. For a New Yorker that doesn’t even have a washer and dryer at home, I certainly didn’t expect that the first time I did my own laundry (like most lazy New Yorkers, I send mine out to a Laundromat) in nearly a year would be in the arctic.

Anyway, a back-in-the-day anecdote by E. J. Corey made it perfectly clear why he had the conference’s first speaker slot. In late 1958, much before his Nobel Prize, he was still a young prof at the University of Illinois, Urbana-Champaign, Corey says he noticed an announcement that a journal called Tetrahedron Letters would be started. With a theoretical paper in hand that needed a home, Corey figured he’d try out the new journal. Lo and behold, his paper was accepted. A surprise came in 1959 when he got a complimentary copy of the inaugural edition of the new journal. Corey told the audience that when he flipped it open, he found his paper not only in the first issue, but on the first page. I just took a quick peek online and found the title: “A theory for the stereospecific polymerization of propylene oxide by ferric chloride,” should anyone be curious.

Not to miss out on the nostalgia, Nobel Prize winner Jean-Marie Lehn also mentioned his link to the journal. Lehn says that two papers published in Tetrahedron Letters in 1969 were some of the first in the area of supramolecular chemistry. But he warned the audience that we might want to brush up on our French, because that’s the language he published them in.