SCIENCE/TECHNOLOGY SCIENCE/TECHNOLOGY noninhibitors and weaker inhibitors are eliminated and progressively simpler sublibraries are constructed until the active agent is identified—a technique developed and reported in Nature in 1991 by Richard A. Houghten and coworkers at Torrey Pines Institute for Molecular Studies, San Diego. Although a cubane-based inhibitor didn't turn up this time, reaction of a pentasubstituted cubane with the same number of amino acids would generate a combinatorial library of more than a million variants. There's a much better chance of finding active compounds in such a library than in the 12,000-member library used in this initial study. A second proposed collaboration is between ARDEC and the Center for Advanced Biotechnology & Medicine at Rutgers University, Piscataway, N.J. This effort will focus on biological activity screening and molecular modeling to identify cubanes with enhanced activity against a range of diseases. ARDEC is also negotiating a CRADA jointly with Geo-Centers, Albert Einstein College of Medicine of Yeshiva University (New York City), and TheraGuide, a biotechnology company in New York City. The goal is to use cubanes to enhance the antiviral activity of alkylureas that Albert Einstein College of Medicine has been developing as anti-AIDS agents. Alkylureas disrupt the lipid bilayer of the AIDS virus, and cubanes are highly lipophilic molecules that bind avidly to the envelope of the virus. "By using these two [types of] compounds in tandem, or by linking them together, we hope to get a synergistic destructive effect on the virus envelope," says Arye Rubinstein, professor of pediatrics, microbiology, and immunology at Albert Einstein College of Medicine. Getting into the military spirit, Rubinstein says cubanes might also be useful as tiny antipathogen or anticancer bombs. The idea is to bind cubanes to monoclonal antibodies and deliver them specifically to pathogens or cancer cells in the body. Energy released from the high-energy cubanes would then be used to destroy the target, he says. "The interaction with the Army . . . has opened a whole new avenue of research in our laboratories," says Rubinstein—adding that "it somehow seems ironic that explosives developed by the Army" are now being developed for therapeutic use as well. • 36
NOVEMBER 28,1994 C&EN
Modern reaction engineering faces challenging real-world problems Joseph Haggin, C&EN Chicago hemical reaction engineering is entering an era of intense application. This modern form of chemical engineering incorporates computational and instrumental advances. And the recent 13th International Symposium on Chemical Reaction Engineering (ISCRE13) held in Baltimore illustrated the broad scope of the discipline—both its international ambience and its various applications. Louis L. Hegedus, vice president of W. R. Grace's research division and a cochairman of ISCRE13, is a vocal advocate of chemical reaction engineering. "Chemical reaction engineering is firmly entrenched and performing well in the chemical industry," he told the symposium. Hegedus points to the contributions of "formal" chemical reaction engineering in developing several of Grace's new, active catalysts for industry. Similarly, symposium cochairman Carmo J. Pereira, a senior research associate at Grace, thinks that "chemical reaction engineering has developed far beyond the core subjects of reactor design, scaleup, and reaction characterization. It has integrated the core subjects with modern computational methods, simulation, and materials design."
C
Formal procedures for designing catalysts have not always been available to chemical engineers. At the symposium, Mark E. Davis, professor of chemical engineering at California Institute of Technology, noted that "catalyst design has been talked about for a long time. In the past... most of catalyst design has been manipulating physical properties of the catalytic materials." Davis wants to put catalyst design on a rational basis. As he points out: "There are many catalytic materials but only a few catalysts." However, although many potentially useful catalytic materials exist, "we have yet to master the practical matters of converting them into usable, reliable, affordable catalysts for commercial use." Catalyst design is another form of chemical synthesis, Davis argues. He regards catalyst design as similar to architectural planning: The architect is told how many rooms of prescribed size and character are needed, the surroundings, anticipated future requirements, available capital, and the like, and the architect creates a structure that incorporates
Davis (above): catalyst design on a rational basis; Rostrup-Nielsen: design based on microkinetic analysis
Chemical engineering responds to changing economic, professional realities The rapid development of chemical engineering during the past 15 years hasn't surprised Milorad P. Dudukovic, who is Laura & William Jens Professor of Chemical Engineering at Washington University, St. Louis, and a cochairman of the 13th International Symposium on Chemical Reaction Engineering held in Baltimore. "The biggest change is that the profession now involves a much greater spectrum of technology/' Dudukovic says. "Chemical engineering used to be largely confined to petroleum and petrochemistry with some inorganic processing thrown in. Now, it is normal to find chemical engineers involved in such diverse things as ceramics, optical fibers, and drug making. The domain of chemical engineering is truly inclusive of everything that involves the transformation of materials. Obviously, chemical engineers are at the center of the craft." Chemical engineers must function in a team ambience as never before. Dudukovic believes that industrial development costs are now too high to be handled by lone entrepreneurs, although a few of these "rugged individuals" remain. "The development of products and processes has become tied to high-tech and high-cost equipment that is usually found only in larger commercial organizations," he says. The dwindling number of independent consultants now finds work most-
this information. The catalyst designer proceeds in much the same way. Davis cites design of a catalyst for the epoxidation of propylene—a major commercial process—as an example. For this process, Shell Chemical uses titanium catalysts supported on silica with tertbutyl hydroperoxide as an oxidant. Shell engineers were faced with the problem that their catalyst is extremely water sensitive. They overcame the problem, Davis says, "by supporting the titanium on a hydrophobic molecular sieve, such as [zeolite] ZSM-5." As such, aqueous hydrogen peroxide could replace the hydroperoxide as the oxidant, and the zeolite screens bulk water from the titanium active site. "The key to success was the hydrophobicity of ZSM-5," Davis points out. In a similar way, Davis hopes to develop a "generic procedure" for making
ly as troubleshooters for the rehab and repair of mature processes that must be resuscitated or modernized. Despite the changes, Dudukovic thinks that training of chemical engineers is not much different from what it was. But emphasis is less on practical skills and more on computational and simulation skills. "This [change] is good or bad, depending on your viewpoint, but it is necessary," says Dudukovic. Although demand for chemical engineers remains good, absolute demand is down. The decline is partly a result of the economy's conversion from a manufacturing base to a service base. Dudukovic believes that internationalization of industry has had little influence on demand for engineers, except that many companies are going overseas for financial reasons, a trend that bothers him. "Whatever they say about it, companies are going overseas because it is cheaper to do so," he says. "We have probably eroded our dominant technical base by capitulating to this demand." And other countries produce engineers who are as well prepared as ours, says Dudukovic, allowing them to fill their own needs quite well. "Since our industrial base is shrinking, we must contract the entire profession," Dudukovic says. He suggests that internationalization is an effect rather than a cause of U.S.
catalysts by using shape selectivity. Davis says, "We are now at an intermediate stage in formal catalyst design, that is, in the practical stage. The future looks good for constructing active-site topology. The computational problems are slowly being solved, but there is a long way to go." Catalyst design tends to focus on specialty chemicals, but interest in new catalysts for high-volume commodity chemicals is reviving. This possibility interests Lanny D. Schmidt, a professor in the department of chemical and materials engineering at the University of Minnesota. Schmidt is exploring partial oxidation with very fast exothermic reactions. The main problem, he says, "is that oxidation reactors are also potentially dangerous and may have low selectivities without good catalyst design." With very fast exothermic reactions,
Dudukovic: no radical changes soon problems. U.S. industry simply has not been able to compete with other countries hungrier to get ahead. Dudukovic expects no radical changes in the profession for the short term. But he does expect to see more successes with chemical reaction engineering, which, he says, will become established "as the modern form of chemical engineering." And he believes that "modern and sound reaction engineering will be the key to successful pollution prevention efforts, since it is the manner in which we conduct chemical transformations that determines whether pollutants are produced or not."
small reactors are adequate and no heat input is required. Reactor design is simpler and, probably, cheaper, but it also demands better specification of the reaction itself. Schmidt is studying catalytic partial oxidation of hydrocarbons to produce synthesis gas with greater than 90% selectivity and 90% alkane conversion and oxidation of olefins with 70% selectivity and greater than 80% conversion. Both reactions involve complete conversion of molecular oxygen. "This can be accomplished with residence times from 10"4 to 10"2 seconds," Schmidt says, meaning that reactors can be two orders of magnitude smaller than reactors used in conventional steam reforming. The feedstocks for Schmidt's reactors have typically been methane and the lower alkanes. Oxidizing these comNOVEMBER 28,1994 C&EN
37
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SCIENCE/TECHNOLOGY SCIENCE/TECHNOLOGY
FOAMS I i m i i . M m n i i N MHI \ p p l i i .ui.mx I in tin- »Mi..I» urn ImliiMrv
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Foams: Fundamentals and Applications in the Petroleum Industry This new volume provides an introduction to t h e nature, formation, propagation, stability, properties, and uses of foams in t h e petroleum industry. Its primary focus is o n t h e applications of the principles of foams and includes attention to practical processes and problems. The volume's twelve chapters are divided into four sections covering: •
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NOVEMBER 28,1994 C&EN
Knshna (above): systematic reactor selection; Schmidt: partial oxidation with very fast exothermic reactions pounds with molecular oxygen invariably causes alarm because of the potential for explosions. But Schmidt believes that this problem need not deter research in this area, because reactant composition can be controlled to safe values. And the reaction velocities are sufficiently fast that the oxygen is totally consumed within 1 mm of the reactor entrance. 'These reactions happen primarily on the catalyst surfaces/' Schmidt says, "and the results are extremely sensitive to the nature of the catalyst. "It is essential to design for the minimization of homogeneous reactions, flames, and explosions. We have done this and have tested the procedure for more than a hundred reactions/' Schmidt's principal reactor is a simple quartz tube with a highly porous catalyst plug. Once the reaction has started, it sustains itself on the catalyst, which usually becomes incandescent. The products are quickly quenched downstream from the reaction site. Quenching most reactions requires no special cooling equipment. Environmental conservation and cleanup are another application area. Jens R. Rostrup-Nielsen, research director for Haldor Tops^e of Denmark, views the challenge as primarily one of obtaining higher selectivities to minimize by-product production. With exhaust cleanup, the problem is designing reactions and reactors that function well when polluting compounds are present at only part-per-million levels. Such demanding application requires basic changes in catalyst design, says Rostrup-Nielsen. "The ultrahigh conver-
sions required in part-per-million reactions may result in the breakdown of the simple . . . approach for formulating reaction kinetics. The classical method of overcoming this problem was to assume a rate-determining step but continue to use the steady-state assumption." A more consistent basis for design should emerge from microkinetic analysis over a wide range of gas compositions. An example of this approach, offered by Rostrup-Nielsen, is development of the procedure for selective catalytic reduction of NOx, which required generating a unique reaction model. In many reaction models, the effects of mixing are critical. Except for laminar flow, fluid mixing traditionally has been treated empirically. Julio M. Ottino, chairman of the department of chemical engineering at Northwestern University, says: "The present treatment of laminar (viscous) mixing is in good shape. This is [because of] developments in chaos theory and the vast improvement in computational resources. There has also been fundamental progress in understanding fluid mechanics in general." Turbulent mixing regimes are not as well defined. No generally accepted model exists that simultaneously aids understanding of the phenomena and provides reliable engineering predictions. 'Typically, turbulent flows exhibit regions of very good and very bad mixing that illustrate the inhomogeneity of such flows," Ottino says. "Current sta-
tistical approaches to the analysis of turbulent flows don't fully deal with these situations/' Reactor design is also changing. Rajamani Krishna, chairman of the department of chemical engineering at the University of Amsterdam, is an active proponent of systematizing reactor selection. "We have developed a systematic procedure for arriving at the 'ideal' reactor configuration for carrying out a desired chemical reaction," he told the symposium. The parameters involved in selection include maximum conversion, maximum selectivity, plant safety, and economic acceptability. Krishna's procedure involves three decision levels. In the first level, catalyst design is the main concern: optimizing the basic catalytic material and adapting it appropriately to the system. Because most of the systems used are fluid systems, often multiphasic fluid systems, a major design variable may be how to generate the maximum extent of a diffusion layer for catalysis. The type of gas-liquid contacting system can be crucial.
The second level looks at mass and energy flows into the reactor. "We must consider step inputs, periodically fluctuating inputs, serial flow introduction, staged- and parallel-flow introduction, [and] the use of membranes," Krishna says. At this level, it is also necessary to consider product dispositions. Sometimes, accumulating products for postreactor separations is the best strategy. At other times, removing the products as they are formed may be better. The final step in reactor selection is specifying the flow regime. The options are numerous and are not always determined by convention. After making the decisions, Krishna appends the "wish list of wants and musts" to arrive at a final reactor configuration. The engineers must still make "educated compromises" if incompatibilities appear. Some observers maintain that chemical reaction engineering came of age a decade ago, but others insist that routine, predictable engineering applications are a requisite for such maturity. ISCRE13 participants think that maturity has arrived. D
Highly electron-deficient porphyrin synthesized The most highly electron-deficient porphyrin known to date has been synthesized by chemists at the University of Pennsylvania, Philadelphia, and the University of Nebraska, Lincoln [/. Org. Chem., 59, 6943 (1994)]. The compound's unusual electrochemical properties suggest uses as a ligand in transition-metal oxidation-reduction catalysts.
Additionally, the perfluoroalkylated porphyrin may act as a catalyst in such unusual phases as supercritical fluids and fluorinated-nonfluorinated solvent mixtures. The generality of the porphyrin synthesis offers possibilities for making other members of this compound class. The new compound is 5,10,15,20-tetra-
Perfluoro substituents create electron deficiency H
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Available Fall 1995 The Fellowship places an ACS member in a staff position in Congress to • Gain firsthand knowledge of the operation of the legislative branch of the federal government, • Make scientific and technical expertise available to the government, and • Forge links between the scientific and government communities. Applications due January 1, 1995. For more information contact: Ms. Caroline Trupp Department of Government Relations and Science Policy American Chemical Society 1155 Sixteenth Street, N.W. Washington, DC 20036, (202) 872-4467. Applications consist of a letter of intent, a resume, and two letters of reference. Arrangements should be made to send the letters of reference directly to ACS. Candidates should contact ACS prior to submitting an application to determine the type of information needed in the letter of intent.
H+
(2)NaBH4
Carbinol C3F7
C3F7
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ACS Congressional Fellowship
VNH
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Oxidation
V-NH F7C:3-VV
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NOVEMBER 28,1994 C&EN
39
