news of the week market its genetically engineered insectresistant corn. The deals are still under negotiation, says a Monsanto spokeswoman, but about $945 million of the acquisition price will suit directly confirms what re be for Holden's. This is a tremendously searchers have assumed from high premium for a privately held compa previous studies: Molecules ny that has annual sales of about $45 mil with amino groups reach out lion. However, what Monsanto will gain to the superconductor surface immediately, suggest chemical industry an through those groups. This alysts, is a worldwide marketing and distri finding is corroborated by elec bution infrastructure for its biotechnology trochemical data indicating products. In addition, says Paul Raman, an analyst that pyridine groups do not chemically interact with the with investment banker PaineWebber in New York City, "Monsanto should be able surface of YBa2Cu307_5. One solution to the problem now has Although the superconductor coun to increase its [seed corn] market share to been devised by Chad A. Mirkin, an associ terpart in this "handshake" and other about 40% from the about 7 to 10%" share ate professor of chemistry, and graduate structural details—such as the degree of it would have had without the acquisition. students Jin Zhu and Feng Xu at North order of the adsorbed molecules—have In a separate deal aimed at agrochemi western University, Evanston, Π1., and Su not yet been determined, McDevitt says cals, Monsanto signed an agreement with san J. Schofer, an undergraduate student at the Raman method should allow a "more combinatorial chemistry company ArQule. Brown University [f. Am. Chem. Soc., 119, complete structural analysis of supercon Under the five-year agreement, the Med235(1997)]. ductor-localized monolayer assemblies." ford, Mass.-based company will provide ar Their solution lies in metal nanopartiThe simplicity of the approach is very rays of compounds for use in discovering cles. Earlier work such as that by the appealing, comments Natan. The monolay and developing crop protection products. group of Michael J. Natan, an assistant er is formed on the substrate by immersing ArQule is to receive $12 million from professor of chemistry at Pennsylvania the substrate in a solution of 4-aminopyri Monsanto for delivering the initial arrays. State University, University Park, showed dine in acetonitrile. Then the monolayer is Additional milestone and royalty payments that assemblies of nanoparticles of metals exposed to gold nanoparticles dispersed in are possible if compounds progress like gold and silver can enhance the Ra toluene and rinsed several times with pen- through field trials and become commer man signals of bulk organic films depos tane. The Raman spectrum obtained after cial products. ited on various substrates. such treatment of the monolayer compares Combinatorial chemistry is most often Building on those results, Mirkin and very well with that of pure solid 4-amino directed toward drug discovery, so part nerships involving small combinatorial coworkers have developed a technique pyridine. compatible with the high reactivity of Maureen Rouhi chemistry firms such as ArQule and major high-temperature superconductors. Using agrochemical producers are rare. But the gold as a Raman-signal enhancer and a same principles can be applied in creating commercially available instrument, they agrochemicals. like drug candidates, com obtained the Raman spectrum of a mono pounds can be rapidly screened and iden layer of 4-aminopyridine on the surface of tified for pesticidal activity. With Monsanthe cuprate superconductor YBa2Cu307_§. "Usually, getting information regarding the surface structure of high-temperature superconductors requires heroic efforts," Monsanto announced three deals last says Natan, an expert in colloid chemistry week—two in seed production and mar and Raman spectroscopy. The experiment keting and one in agrochemicals—that by Mirkin and coworkers is simple and will expand its technology base and pro straightforward, rapidly giving insight into vide commercialization routes for its bio the structure of the organic film, he adds. technology developments. Mirkin's research provides, for the first In the two largest deals, Monsanto time, information about the "handshaking will spend a total of up to $1.02 billion mechanism" between a monolayer and a to acquire Holden's Foundation Seeds complex cuprate superconductor surface, and two Corn States businesses. Based in notes John T. McDevitt, associate profes Williamsburg, Iowa, Holden's is a leading sor of chemistry at the University of Texas, producer of seed corn used by retail Austin. One of McDevitts areas of exper companies to create hybrid seeds for tise is chemical modification of high- farmers. Des Moines-based Corn States temperature superconductors. Hybrid Service and Corn States Interna The Raman spectrum indicates a strong tional are the exclusive worldwide mar chemical interaction between the amino keting and sales representatives for Hold group of 4-aminopyridine and the en's products. Late last month, Monsanto YBa2Cu307_5 substrate, Mirkin says. This re- received final U.S. regulatory approval to Shapiro: deals will speed seeds to market (From left) Zhu, Mirkin, and Xu are three-fourths of team that devised spectroscopic technique.
Monsanto to buy seed corn producer, makes agchem discovery deal
6 JANUARY 13, 1997 C&EN
to, the target chemicals will include herbicides, fungicides, and insecticides. In the past 18 months, Monsanto has spent more than $400 million to expand its reach in agricultural biotechnologyacquiring stakes in Calgene, Ecogen, DeKalb Genetics, and all of Agracetus— fueling rumors, since proven true, that the company would split into a chemical company and a life sciences company (C&EN, Dec. 16, 1996, page 9). Holden's basic seed technology will be an important building block in Monsanto's agricultural biotechnology business, providing a delivery mechanism for getting genetically engineered plant traits into commercial seed products. "These acquisitions mean the latest technological advances will be made available to the greatest possible number of seed companies of all sizes with unparalleled speed," says Robert B. Shapiro, Monsanto chairman and chief executive officer. Monsanto's investments in seed marketers are designed to allow it to capitalize on the billions of dollars it has invested in plant biotechnology R&D over the past 20 years. Ann Thayer
Investors push for Rexene sale Two Wall Street investors are waging a battle to toss out the current board of directors of Dallas-based plastics and film maker Rexene. They want to install four new directors whose mission will be to sell Rexene for at least $16 per share or $300 million. The investors are miffed because they say Rexene's board failed to adequately explore at least three offers to purchase the company made last year by Salt Lake Citybased plastics maker Huntsman Corp. In July, Huntsman offered $14 per share (C&EN, Jury 29, 1996, page 6); it made another offer of $15 in August (C&EN, Aug. 12,1996, page 9); and it made a third offer of $16 late in October. The last offer represented a more than 70% premium over the $925-per-share price at which Rexene traded before Huntsman's first offer. The investors' proposed directors "have no experience in managing a specialized polymer company like Rexene," warns Rexene's chairman and chief executive officer, Andrew J. Smith, in a letter to shareholders. If they secure control of Rexene and cannot sell the company at $16 per share, the proposed
directors would be "forced to manage the company, or sell the company at an unacceptably low price," he says. However, in reaction to the two investors' call for the sale of the company, Rexene management now says it would consider selling the company for $16 per share, if it could close a deal within 60 days. At press time, Rexene, which has annual sales of more than $600 million, traded at $ 14 per share on the New York Stock Exchange. The investors, Wyser-Pratte Management and Spear, Leads & Kellogg, both of New York City, together own about 10% of Rexene's shares. They have just mailed a solicitation statement asking shareholders to approve a special meeting of shareholders. If a majority approves the request, the investors—who plan to ask Smith to remain as a fifth director and CEO—hope that the shareholders will replace the current board with their nominees. Those nominees are Jonathan R Macey, a professor at Cornell Law School; Robert C. Mauch, former president and CEO of propane distributor AmeriGas; Lawrence C. McQuade, former executive vice president of W.R. Grace; and James S. Pasman Jr., former chairman and CEO of KaiserTech, an aluminum and chemical concern. Of the current imbroglio, a spokesman for Huntsman says, "We are aware of the proxy battle, but we have nothing to do with it." The spokesman added that under advice of counsel, he could make no comment about Huntsman's interest in acquiring Rexene. If Huntsman is still interested in acquiring Rexene, it may not want to re-create the hostile atmosphere that existed between the two companies last year. Marc Reisch
Methylene chloride exposure sharply limited The Occupational Safety & Health Administration has issued a final standard limiting worker exposure to methylene chloride. The new eight-hour time-weighted permissible exposure limit (PEL) is 25 ppm. The previous PEL was 500 ppm. According according to OSHA, about 238,000 workers in more than 92,000 establishments are exposed to methylene chloride every year. The compound is used for paint stripping and in aerosols, plastics manufacture, metal-degreasing operations, urethane foam production, and pharmaceuticals. It is not flammable and does not contribute significantly either to
air pollution or depletion of stratospheric ozone. OSHA has set the new standard low because of indications that methylene chloride is carcinogenic. Laboratory animal studies show that it can cause cancers in rats and mice, and some epidemiologic data indicate it may cause cancer in exposed workers. Based on OSHA's risk assessment from these data, the agency estimates that exposure at 25 ppm will result in 3.6 excess cancer deaths per 1,000 workers exposed to the chemical. These risks are vigorously denied by the Halogenated Solvents Industry Alliance (HSIA), a Washington, D.C.-based trade group that represents manufacturers and users of methylene chloride. OSHA's review of the toxicity of methylene chloride "likely will be inconsistent with the outcome of an ongoing recharacterization of the solvent by the Environmental Protection Agency and other federal agencies," predicts HSIA Executive Director Peter E. Voytek. He believes this ongoing federal review will show that it is safe to use the chemical at the industry-recommended exposure level of 50 ppm. OSHA disagrees. Adam M. Finkel, director of OSHA's health standards programs, says industry is incorrect in believing OSHA has not considered the animal and epidemiologic data properly. "OSHA has considered the metabolic differences between mice and humans and did consider the data submitted to us by HSIA," Finkel says. Those data did not convince the agency to set the PEL at 50 ppm. HSIA is also concerned that it will be impossible for small businesses to meet the new, tougher standard. "For many smaller users, if OSHA sticks with the 25 ppm, they will go out of business," according to Voytek. OSHA believes its standard is both technologically and economically feasible. Compliance costs are estimated to be $101 million annually, or about $424 per exposed worker. Firms that substitute other chemicals for methylene chloride could avoid compliance costs entirely, OSHA points out. At press time, the methylene chloride standard had not yet been published in the Federal Register, but it will go into effect 90 days after publication. It includes requirements for exposure monitoring, medical surveillance, and respiratory protection. Small businesses get a few breaks on some compliance deadlines and medical tests, but will have to meet the same exposure limit as all other affected operations. Dave Hanson JANUARY 13, 1997 C&EN 7
