An ongoing program in plant mo lecular biology lowers the thresh old of effort required for a newly recruited scientist to get his own projects under way, Hein says. Such a new scientist "can plug in very easily" to the PPG group and not have to start a project from scratch. What PPG is seeking from the program at Scripps, Chakrabarti says, are "scientific signals." He defines a signal as a "piece of basic research information one can mold into a commercial product." One such signal has come from t h e work of Darryl Rideout, a Scripps chemist who was brought on board as part of the PPG re search program. Rideout last year published research on what he calls "self-assembling cytotoxins." The ba sic idea is to administer two rela tively nontoxic compounds that react spontaneously to form a highly tox ic compound in vivo. Using two compounds allows one to amplify slight differences in distributional selectivity for each of the initial compounds. Rideout has demonstrated the con cept working with erythrocytes. Decanal, an aldehyde, and N-aminoN'-l-octylguanidine (AOG), a hydra zine, react under physiological con ditions to form the h y d r a z o n e N-decy lidenimino-N'-1 -octy lguanidine (DIOG). Neither 56μΜ decanal nor ΙΟΟμΜ AOG alone is toxic to erythrocytes, Rideout found. How-
Chakrabarti: seeking scien tific signals
ever, a mixture of 28μΜ decanal and 28μΜ AOG lyses erythrocytes. Studies show that DIOG formed by the reaction of decanal and AOG is the toxic agent. Even though DIOG lyses erythrocytes at lower concentrations than the decanalAOG mixture, what is important is that the dose-response curve for the mixture is much steeper than that for DIOG alone. Selectivity is the goal for com mercial chemicals ranging from anti cancer agents to herbicides, Rideout explains. The idea is to kill one type of cell—tumor cells or weeds, for instance—and leave others alone. But selectivity is only part of the equation. If the dose-response curve is relatively flat for a chemical with, say, a slight affinity for rapidly di viding tumor cells, then any dosage that kills most of the tumor cells will also kill a significant percent age of normal cells. A steep doseresponse, on the other hand, allows one to take advantage of relatively slight differences in affinity for the two types of cells. In the jargon of the business, a steep dose-response curve opens up the "therapeutic window." Enhancing distributional selectiv ity through a biomolecular reaction to form the cytotoxin seems to be a general phenomenon, Rideout says. He has demonstrated it in fungi, bacteria, and a tumor cell line. He points out that many compounds that exhibit slight selectivity exist; however, that selectivity is insuffi cient to be exploited in commercial products. "There are a lot of com pounds sitting on the shelf, so to speak, that can now be taken off the shelf and used in a self-assem bling cytotoxin in such a way that their selectivity becomes interest ing," he says. "This is a very powerful concept," Chakrabarti says, and one that PPG will be pursuing both for develop ment of potential herbicides and for development of pharmaceuticals, be cause Johnson & Johnson decided not to exercise its rights to the re search. Chakrabarti isn't willing to speculate on why Johnson & John son was not interested in the re search. Whatever the reason, he says, "we didn't miss it." Rudy Baum, San Francisco
Monsanto improves glass interlayer process Monsanto has been making ther moplastic sheets with tinted color gradients since the 1950s. But novel technology commercialized more re cently has pumped new life into the product. The thermoplastic sheets are in tended for use as interlayers be tween sheets of glass for vehicle windshields or in architectural ap plications. Monsanto's new Saflex process has substantially reduced production costs, improved product quality, and enhanced Monsanto's market position. It also has earned the employees who developed it rec ognition by the company. Saflex interlayers are polymer sheets imbedded between layers of glass to improve safety by limiting danger from flying glass following an impact. Most interlayers made today are also colored for control of incident sunlight. Therein lies a problem. It is desirable to vary the density of the color across the glassinterlayer composite. Typically, a windshield is more densely colored at the top. Prior to development of the new Saflex pro cess, the conventional procedure for making tinted gradient interlayers was to print, dip, or spray pigment or dye on. the extruded interlayer. Achieving the necessary diffusion of dye throughout the polymer re quired weeks of curing under close temperature control. And this re quirement meant that large inven tories of products had to be main tained in controlled environments. There were consequent quality con trol problems and the correspond ing expense. The solution to the problem of cutting production costs and improv ing quality control was conceived by Hagop Boyajian, senior group leader; Robert A. Esposito Jr., se nior research engineer; and William W. Mumford, an engineer now re tired, all of Monsanto's resins divi sion in Springfield, Mass. Their so lution involved the coextrusion of a dye layer within the extruded ther moplastic interlayer. The dye is coextruded in such a way that the color density of the band varies in a February 16, 1987 C&EN
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Technology oxides, and biological materials. For example, makers of emulsion poly merized resins may verify lot-to-lot uniformity. Or ceramics producers may work toward uniform particle sizes for lower sintering tempera tures. The user injects about 50 μΙ, of a 1% suspension. An initial flow of water containing small amounts of surfactant, electrolyte, or buffer moves the sample into a circular, hollow band 60 cm in circumfer ence, 25 mm wide, and 250 μιη thick. Spinning of the band in a centri fuge establishes an equilibrium, with heavier particles or macromolecules closer to the channel wall, while Brownian motion keeps lighter bod ies closer to the center. Resumption of liquid flow results From left, Esposito, Mum ford, Boyajian and windshield tinted by Saflex process in laminar (layered) flow. Layers of prescribed manner. The trick lies in factured in Belgium and Japan, as liquid close to channel walls flow slower than those toward the cen using a wedge-shaped nozzle for well as in the U.S. the dye layer. Success of the process has resulted ter. Lighter particles closer to the Normal coextrusion processes are in recognition of the developers center thus elute first. Users can difficult to control, especially if a with the 1986 Edgar M. Queeny enhance resolution by programing gradient colorant band is required. Award—a gold medal, and $80,000 an exponential reduction in the cen The color dispersion must be ex shared by the recipients. The award trifugal field during a run. This is tremely even with no color varia is given by Monsanto for develop analogous to temperature program tions other than the gradual reduc ment of unique proprietary tech ing in gas chromatography or sol tion of color density. The color cut nology that has resulted in an iden vent gradient programing in liquid chromatography. off point also must be uniform across tified commercial success. the glass composite sheet. This re Joseph Haggin, Chicago The technique is one of many quirement presents a demand that field-flow fractionation methods de there be no variation in polymer veloped over the past 25 years by melt flow in the extruder, a formi analytical chemistry professor J. dable control problem. Calvin Giddings at the University of Utah. Du Pont has licensed The polymer used for the interGiddings' patent, and its own sci layer can be anything that is capa ble of extrusion through a sheet die. A sedimentation field-flow fraction entists have worked to shorten run The preferred polymer is plasticized ator that separates and character times. polyvinyl butyral. Others that have izes particles and macromolecules Stephen Stinson, New York been used include polyacrylics, poly has been introduced by Du Pont. styrenes, polyvinyl ethers, polyvi Priced at $89,000, the instrument nyl acetals, and polyurethanes. resolves particles according to size In a typical operation, a polyvi from 10 nm to 1 μιη and macromol nyl butyral sheet is extruded with ecules according to molecular weight an encapsulated color gradient band from 106 to 1013 daltons in less than along one edge. Clear polyvinyl bu one hour. The electronics and the biotechnoltyral is the sheet material; the dye Populations of particles that dif ogy/bioprocessing industries are material is typically a predyed mix fer in size by 10% are well resolved two of the current driving forces ture of the same polymer as the by the instrument, the company for improved filtration/separation sheet. In the case of polyvinyl bu says. Precision of determinations is technology that have boosted prod tyral, processing temperatures range about 1%. Samples may be collected ucts for that technology to what is from 190 to 205 °C. in a fraction collector after detec now a $3.5 billion business in the The Saflex process has cut pro tion of each fraction. The process is U.S. And few product segments in duction times from months to hours, gentle enough to avoid damaging that business are growing at less than 5% per year, with many post substantially improved product qual proteins, nucleic acids, or viruses. ity, and produced sharply increased The device may find use in char ing figures of more than 8%. customer demand. Saflex interlayer acterizing materials such as poly These are a few of the overall composites are now being manu mer latexes, pigments, fillers, metal figures contained in a new market
Du Pont offers fast field-flow fractionator
Separation products market hits $3.5 billion
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February 16, 1987 C&EN
