be any more burdensome than what is al­ready required.

But Adams points out that USDAs scrutiny of university labs is much more in­tense than that of federal labs. For exam­ple, USDA does not inspect federal labs nor have federal labs had to fill out daily forms showing that they are complying with the rules. The big unknown is what any new rules will actually require. Just changing the cage sizes for rodents could have a huge financial impact, he says.

On another front, a bill now being considered in the House and Senate could reduce the number of lab animals needed for research. The Interagency Coordinating Committee on the Valida­tion of Alternative Methods Authoriza­tion Act of 2000 would officially sanction an informal interagency process for vali­dating new, revised, or alternative toxi-cological test methods. If passed, this legislation is expected to lead to greater use of in vitro methods.

The American Chemistry Council (formerly the Chemical Manufacturers Association), animal rights groups, and the Administration all support the legis­lation, which is expected to pass before the 106th Congress adjourns for good.

Bette Hileman

Left-handed DNA Finally Gets Some Recognition A scientific team has achieved a long-sought advance in the search for com­pounds capable of recognizing and mod­ifying DNA on the basis of its shape—as opposed to its sequence, the more com­monly used basis for DNA binding and manipulation.

The group shows that WP900, the en-antiomer of the anticancer natural prod­uct daunorubicin, binds selectively to a left-handed (Z-DNA) form of a synthetic DNA polynucleotide. The researchers also demonstrate that the newly synthe­sized enantiomer can be used in conjunc­tion with daunorubicin—which was al­ready known to recognize right-handed DNA (B-DNA)—to interconvert the polynucleotide back and forth between its left- and right-handed forms.

The findings could lead to the ratio­nal design of drugs for diseases such as cancer in which altered forms of DNA may play a causative role. In a commen­tary scheduled to appear in the Proceed­ings of the National Academy of Sciences USA, pharmacology professor Michael J.

Waring of the University of Cambridge notes that the group's results are "of clas­sic significance."

The work was carried out by biochem­istry professor Jonathan B. Chaires of the University of Mississippi Medical Center, Jackson; professor of medicinal chemis­try Waldemar Priebe of the University of Texas M.D. Anderson Cancer Center, Houston; assistant professor of medicine John O. Trent of the University of Louis­ville; and coworkers [Proc. Natl Acad. Sci. USA, published Oct. 10, Early Edi­tion, http://www.pnas.org/papbyrecent. shtml].

The study was based on speculation by Chaires, Priebe, and coworkers that daunorubicin's enantiomer might bind DNA of opposite handedness from B-DNA. Priebe and postdoc Izabela Fokt first designed and carried out a total syn­thesis of WP900, an arduous process that required 33 synthetic steps. Although B-and Z-DNA are not mirror images of each other, Chaires and postdoc Xiaogang Qu found that WP900 bound Z-DNA selec­tively. Trent aided the effort by develop­ing a predictive molecular model for the binding of WP900 to Z-DNA

"A striking result in our study is that in addition to selectively recognizing partic­ular DNA conformations, daunorubicin and its enantiomer can actively convert DNA to the conformation that provides the preferred binding site for each enan­tiomer," Chaires tells C&EN. "No chiral complex has shown such an activity."

Most agents known to recognize DNA shape are chiral metal complexes. In 1976, physical chemistry professor Bengt

Nordén and a coworker at Chalmers Uni­versity of Technology, Goteborg, Swe­den, first reported the selective binding of a tris(dipyridyl)Fe(II) complex to B-DNA. And chemistry professor Jacque­line K. Barton of California Institute of Technology has discovered a variety of chiral metal complexes with selective af­finity for B-DNA

Small organic molecules that show enantiomeric selectivity for B-DNA have also been identified by chemistry professor Samuel J. Danishefsky of Me­morial Sloan-Kettering Cancer Center and Columbia University and his co­workers and independently by the group of Dinshaw J. Patel, head of Me­morial Sloan-Kettering's Nucleic Acid & Protein Structure Laboratory.

"This is not the first time that a ste­reoselective ligand capable of binding to Z-DNA has been described," Waring notes of the new study, "but it does seem to be the first unambiguous dem­onstration of true selectivity for left-handed DNA over right-handed DNA . . . The binding constants are not enor­mous, but they are sufficient to nudge [interconversion of] the polymer in one direction or the other."

WP900 also turns out to be cytotoxic to cancer cells, making it a possible lead compound for Z-DNA-targeted antican­cer agents. In future work, Chaires, Priebe, Trent, and coworkers plan to study WP900's mechanism of action and create modified versions that may have higher binding affinity and selectivity for Z-DNA Together with Houston Pharma­ceuticals, a company founded by Priebe,

Daunorubicin binds by intercalation with B-DNA (left), whereas its enantiomer, WP900, binds in a similar manner with Z-DNA (right).

OCTOBER 16, 2000 C&EN 7

n e w s of t h e w e e k

they will seek out small-molecule drugs that target different forms of DNA as a means to control gene expression.

Barton comments that "a specific role for the Z-DNA conformation in vivo has remained elusive. Perhaps [WP900], in showing selectivity for Z-DNA and driv­ing transitions, might be useful in explor­ing therapeutic consequences of Z-DNA targeting. However, the binding affinities of the compounds are modest, and it will be quite a challenge to establish such tar­geting in vivo."

Stu Borman

Magnesium Systems Could Rival Current Lead-Acid Batteries

Rechargeable magnesium battery sys­tems developed in Israel could rival the performance of environmentally prob­lematic batteries used in electric vehi­cles and other heavy-load applications, according to the discovery team.

The prototype systems, devised by Doron Aurbach, head of the electro­chemistry group, and coworkers at Bar-Ilan University, Ramat Gan, comprise a magnesium metal anode; novel electro­lyte solutions based on magnesium-organohaloaluminate salts; and a cath­ode made from a novel material that contains magnesium, molybdenum, and sulfur [Nature, 407, 724 (2000)].

The group notes that magnesium is abundant, inexpensive, easy to handle, environmentally benign, and—because the metal is light—has potential as a high-energy-density power source. Re­chargeable lead-acid and nickel-cad­mium batteries currently employed in large-scale energy conversion, on the other hand, contain heavy metals that are highly toxic.

"Our battery systems are green, can deliver thousands of charge-discharge cycles with very little capacity fading, and are operational over a wide temperature range," Aurbach tells C&EN. 'They have a very long shelf life and are expected to be cheaper than other rechargeable bat­tery systems on the market."

According to Jeffrey R. Dahn, a phys­ics and chemistry professor at Dalhou-sie University, Halifax, Nova Scotia, and an expert on battery materials, the work is impressive. "I don't think anyone has developed a rechargeable magnesium system before that was worth anything,"

he remarks. "The fact that the group can achieve so many charge-discharge cycles with very low capacity fading is amazing."

Dahn explains that one of the main problems that has hindered development of magnesium systems in the past has been the reaction of magnesium anodes with electrolytes, resulting in growth of passivating surface films on the anodes that inhibit electrochemical reactions.

"The magnesium electrodes are not passivated in the electrolyte systems used by Aurbach's group," Dahn says. "That's really important because it gives the 100% cycling efficiency of the mag­nesium that is required for the long cy­cling life of the system."

Aurbach and colleagues point out that their present results are only the first step in the development of this technology. The team is working on in­creasing the voltage of its batteries and notes that the energy density of re­chargeable magnesium batteries could be considerably increased by modifying the cathode by, for example, doping with electropositive atoms.

Michael Freemantle

Asbestos Drives Owens Corning Into Bankruptcy Building and composite materials maker Owens Corning has filed for reorganiza­tion under Chapter 11 of the U.S. Bank­ruptcy Code. A flood of new liabilities related to its long-dismantled as­bestos products business and cooling demand for its current portfolio were more than the company could bear.

Owens Corning has already agreed to pay $5.2 billion to people whose health has been impaired because of the use of asbestos insulation it sold un­der the Kaylo brand name between 1952 and 1972. The amount covers more than 320,000 claims evaluated before and af­ter a national settlement program was set up almost two years ago.

Owens Corning has an additional 150,000 claims pending under the na­tional settlement program—totaling about $1.3 billion—and another 30,000 claims from people who are not partici­pating in the program. The total payout for these suits has yet to be resolved.

OWENS CORNING

The company is also a victim of ris­ing interest rates and easing demand for its glass fiber insulation and other build­ing products. For the second quarter of 2000, its net sales decreased 1% to less than $1.3 billion.

Owens Corning is not going out of business, only negotiating with credi­tors on how it can best reorganize to meet its obligations. That may involve setting up a trust, which would be sepa­rate from the company, to handle the claims and insulate the company itself from mounting liabilities.

The company has been given a $500 million line of credit from the Bank of America to keep its business afloat. During the Chapter 11 proceedings, the company will suspend payments for div­idends, on unsecured debt securities, and to asbestos claimants.

"Until very recently, we thought Chapter 11 could be avoided," says Glen H. Hiner, Owens Coming's chairman and chief executive officer, noting that the company tried out-of-court settle­ments and legislative and judicial relief and formed its national settlement pro­gram, all to manage the liabilities. "However, the cost of resolving current and future claims, together with a flurry of recent new filings from plaintiff law­yers not participating in the [national settlement program], led us to the con­clusion that a Chapter 11 reorganization was prudent and necessary."

Companies facing similar circum­stances because of as­bestos have, on average, been in Chapter 11 for six years, Owens Corn­ing says. Hiner hopes that the company can re­solve these issues in half that time.

Other makers of as­bestos products have weighed in on Owens Coming's predicament. W.R. Grace, which has

its own liabilities and is paying more than $1 billion in damages, says it is important for companies facing such turmoil to be healthy so they can compensate their claimants.

USG Corp. distanced itself from Owens Coming. "USG Corp. is in a very different situation than Owens Corning. USG's cash flow and balance sheet are strong, and U.S. Gypsum's asbestos exposure has historically been far less than theirs," says William C. Foote, USG's chairman.

Alex Tullo

8 OCTOBER 16, 2000 C&EN