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derstanding of how proteins interact with RNA.
"Just seeing the architecture of how this whole thing is put together is neat!" Steitz says. "I think it's going to be an incredible database for understanding how RNA folds. Everybody—including ourselves—will look at this RNA structure and ask: What are the principles of folding in RNA? And can we use these principles to predict the structure of other RNA?"
At least one atomic resolution structure of the other subunit of the ribosome is expected shortly. Venki Ramakrish-nan, an investigator at the Medical Research Council Laboratory, Cambridge, England, says he has two papers on this structure in press, including views of the subunit complexed with three different antibiotics. Both the Yale and Cambridge groups published lower resolution structures of their respective sub-units last year (C&EN, Aug. 30, 1999, page 14).
Like Ramakrishnan, the Yale group is also investigating the interactions of their subunit with various antibiotics. "We are going to be able to get involved in structure-based drug design with our structure at quite a respectable level, I believe," Steitz says. The ribosome is one of the most important targets of existing antibiotics, he notes, which makes it of prime interest for future drug design. Although their plans are still in flux, Steitz anticipates that the Yale group will start a small biotechnology company in New Haven that will work with various pharmaceutical houses on structure-based drug design.
Rebecca Rawls
Profits Up For German Chemical Producers The first half of this year smiled on German chemical companies, according to results released last week by major producers BASF, Bayer, Celanese, and SKW. But one or two niggling signs in second-quarter results indicate that raw material and energy cost increases are starting to eat into profitability.
At BASF, which is the world's largest chemical company, first-half sales were $15.7 billion, up 24.5% from the comparable period in 1999. Net income was $820 million, an improvement of 113%. Second-quarter sales of $8.07 billion set
a record, BASF said. Net profits for the second quarter were $403 million, an increase of 323%, reflecting large extraordinary charges taken in the second quarter of last year.
Second-quarter operating profits before special charges were $794 million, up 18% over the same period in 1999. However, the company said, "a number of divisions were exposed to noticeable pressure on margins, as a result of increased raw material prices. To date, this effect has been only partially offset by increases in selling prices."
First-half sales from continuing operations at Bayer totaled $13.9 billion, up 22% from the same period of last year. However, first-half net profits declined 40% to $929 million. Last year's first-half figures included nearly $900 million in revenues from the spin-off of the company's Agfa photographic division.
In the first six months of the year, Bayer rang up double-digit sales growth in all of its business segments and regions, while operating profits improved for all divisions except its chemicals unit. There, though sales rose 17% over first-half 1999 to $1.89 billion, operating profits declined 4% to $223 million because of "sharp increases in raw material prices." Conversely, operating profits for Bayer's health care operations rose 68% to $672 million on sales of $4.26 billion, a 21% increase.
At Celanese, second-quarter sales were up 19% to $1.17 billion, and operating profits were up 69% to $99 million. The company posted net profits of $23 million in the quarter, compared with a loss of $200 million in second-quarter 1999, engendered by Celanese's split from Hoechst last year.
The operating profit margin for the second quarter, excluding special charges, was 8.5%, up 6% from the second quarter of last year. However, the comparable figure in the first quarter of 2000 was 13.9%. Claudio Sonder, Celanese chief executive officer and chairman, said, "We did not perform as well as in the first quarter, largely because of rapidly rising raw material and energy costs."
SKW, in one of its last reports prior
to its merger with Degussa-Hiils later this year, showed "a very successful first half," the company said. "The strong growth seen in the record figures both last year and in the first quarter of 2000 con
tinued at the same pace in the second quarter," with
sales and operating profits increasing "substantially."
Sales for the half were $1.86 billion, up 27% over first-half 1999;
operating profits were up 21%
to $277 million. All four of the compa
ny's divisions—construction chemicals, nature products, perfor
mance chemicals, and oligomers/silicones—contributed to the growth, SKW said.
Patricia Short
Nuclear Weapons: Cleanup Without End Forever is a long time, but that's how long watchful monitoring and isolation from humans will be required at more than 100 former U.S. nuclear weapon sites, a National Research Council report says.
Department of Energy cleanup plans for these sites, the report says, do not fully recognize the role of long-term stewardship, nor the likelihood that engineered barriers and other techniques used to isolate radioactive and hazardous waste will fail long before time has rendered the wastes safe.
The report questions DOE assumptions that site stewardship will be a low-cost operation, compared to the $250 billion cleanup price tag. Stewardship could stretch to thousands of years, the report says, and costs could skyrocket if DOE scientists underestimate the price of solutions to difficult cleanup problems, such as the flow of contaminated groundwater.
Because of the extreme timescale, the report says, stewardship must include careful watching of land use near sites, especially in rapidly growing areas such as Denver, near the Rocky Flats site, and Las Vegas, near the Nevada Test Site.
Monitoring and oversight must entail more than signs, fences, or deeds
10 AUGUST 14,2000 C&EN
of sale. The report singles out DOE's Oak Ridge facility in Tennessee, where land sold to a golf course developer carried the stipulation that contaminated groundwater not be tapped. Despite the restriction, however, the owner soon began drilling for water.
The report also notes that technical solutions may not work or may take hundreds of years. It cites a groundwater containment operation at the Han-ford Reservation in Washington state intended to retard migration of strontium-90 to the Columbia River. Strontium-90 has the benefit of a short, 29-year half-life, compared with other radioactive wastes, but the pump and reinject facility at Hanford will have to run for 300
| Columbia River flows ο through DOE's Hanford I Nuclear Reservation.
years for radiation to decay to safe levels.
The report urges DOE to fully integrate stewardship into cleanup plans.
DOE commissioned and agrees with much of the report, says Gerald G. Boyd, deputy assistant secretary for science and technology in
DOE's Office of Environmental Management. DOE must actively monitor for "100, 200, or 1,000 years—whatever it takes," he says, "but we think we can lay out a cost-effective program."
Using the Hanford example, he says, 'We may find a better way to treat strontium in groundwater in the future, cutting costs and time." He argues, however, that DOE can't wait for long. "We need to get the waste stable and in a safe condition quickly," he says.
DOE created a Long-Term Stewardship Office last November with a $5 million yearly budget, Boyd points out. It will issue a stewardship assessment in October.
Jeff'Johnson
Nature Spurs Design Of Iron-Oxo Complex Taking their inspiration from biological reactions, chemists have succeeded in synthesizing a unique artificial iron-oxygen complex that's not only stable enough to be characterized, but also provides a new springboard for study and design of catalytic complexes.
Nature routinely performs oxidation with the help of iron-containing catalysts that activate molecular oxygen. It's believed that heme enzymes such as cytochrome P450 and non-heme enzymes such as methane mo-nooxygenase split 0 2 apart, grabbing one of the oxygens and forming an intermediate oxo complex. These complexes then go on to perform chemical reactions, like the oxidation of methane to methanol.
Top view ofiron-oxo complex reveals cavity formed by the ligand surrounding oxygen (red). Iron is shown as orange;
carbon, gray; hydrogen, white; and nitrogen (barely visible), blue.
But these intermediates have been notoriously difficult to pin down. The structures of synthetic heme-based complexes have been moderately characterized, but the structures of non-heme-based complexes had until now only been inferred from mechanistic studies. And attempts to synthesize arti
ficial nonheme iron-oxo complexes have been hindered by the fact that the molecules tend to form unreactive, oxo-bridged dimers.
The new synthetic monomelic iron-oxo complex, which doesn't suffer from such limitations, was created by associate chemistry professor Andrew S. Borovik and graduate student Cora E. MacBeth at the University of Kansas in Lawrence, associate chemistry professor Michael P. Hendrich at Carnegie Mellon University in Pittsburgh, and their colleagues.
Knowledge about biological processes gave them insight into how to design the synthetic system, MacBeth says. 'The best way to couch it is to say that it's bioinspired," Borovik says.
Their success hinges on the design of a new ligand system—which colleagues have described as elegant— that forms a cavity, surrounding the oxygen atom of an Fe-0 unit with stabilizing hydrogen bonds [Science, 289 , 938 (2000) ]. The authors say this type of hydrogen bonding near unsaturated metal centers is probably what's going on in the complex's biological analogs. Hydrogen-bond donors have been proposed in heme enzymes such as cytochrome P450, and although the picture is muddier in the case of nonheme enzymes, Borovik says, "there's a reasonable amount of evidence that hydrogen bonds play a crucial role in regulating dioxygen activation."
One unique aspect of the system is that two of the iron-oxo complexes are formed from 0 2 activated by the complex's precursor, as opposed to the one complex formed in biological systems.
'Without a doubt, these complexes are benchmark structures for our understanding of nonheme metallopro-
teins and their 0 2 activation," notes Karl Wieghardt, chemistry professor and managing director at the Max Planck Institute of Radiation Chemistry, Mulheim an der Ruhr, Germany.
Calling the research "a big advance in bioinorganic chemistry," H. Holden Thorp, associate chemistry professor at the University of North Carolina, Chapel Hill, says the ligand design has great tailoring potential. And the group members now want to do just that: By manipulating the li-gands, they say they may be able to tune the molecule's reactivity.
Elizabeth Wilson
AUGUST 14, 2000 C&EN 11