Chemical & Engineering
NEWS FEBRUARY 13, 1967
The Chemical World This Week Magnetic bottle quiets plasma Containment and control of plasma has been achieved in a magnetic bottle at the University of Wisconsin by graduate student research workers John A. Schmidt, J. Clint Sprott, and Donald E. Lencioni, working under the direction of physicist Donald W. Kerst. The apparatus used generates an octupole toroidal furnace, a magnetic field formed by four current-carrying hoops. The device was designed and built at the university and has now been perfected to a point where a quiet and stable plasma is contained in a closed system. Work by former graduate students also contributed to the achievement, Dr. Kerst said at the annual meeting of the American Physical Society, held in New York City. The encouraging development, Dr. Kerst notes, has opened the door to research on methods to control and capture the energy released by thermonuclear reactions. The Wisconsin workers ran their first experiments in 1964. Scientists at General Atomic division of General Dynamics then built a similar device and corroborated the Wisconsin results (C&EN, Nov. 14, 1966, page 4 7 ) . A quiescent plasma was also observed in a stellerator by West German scientists. At Wisconsin, Dr. Harold K. Forsen cooperated in modifying the octupole device to give a system similar to a stellerator. In the Wisconsin system, a plasma cloud was injected through the multipole magnetic field from the outside at a point where lines of force were concave toward the oncoming plasma. Two actions caused penetrations of the field by plasma: Ions are deflected in the magnetic field in one direction while the electron component in the plasma bends in the opposite direction. This charge separation produces opposite charges on the opposing boundaries of the particle cloud. Polarization thus cancels the magnetic force on the moving ions, permitting the cloud to drift across the magnetic field, Dr. Kerst says. In operation, the apparatus injects plasma of about 100-e.v. ion energy into the octupole magnetic field. A zero field locus is near the middle of
Graduate students and plasma confinement system A quiet and stable plasma the region, and fields of 1000 to 8000 gauss exist along the wall and around the current-carrying loops forming the multipole field. Probes and microwave observations show that the electron component has 10-e.v. (about 120,000° K.) temperature and remains for 2.5 milliseconds. The energetic ions were extracted from the plasma to determine the energy and lifetime of the ions for the same period of time. There were no sudden or catastrophic losses or fluctuations in either the central or extracted plasma which would indicate instability, according to Dr. Kerst. After 100 microseconds, the large electric fields present during filling died away and the plasma apparently acquired a boundary with small electric potential differences, compared to the 100-e.v. energies of contained ions. This quiescent condition, according to the Wisconsin scientist, continued while the plasma was gradually being lost on probes and supports. The development of plasma confinement apparatus is paralleled by research on techniques for improving plasma injection devices. Such devices are needed before the full potential of experimental (and eventually practical) plasma reactors can be re-
alized. Research on the Madison campus is now under way to devise techniques for efficient continuous plasma creation and injection. One source currently being used is the E X B (or rotating plasma) source, characterized by two inherent problems: limited gyromotion conversion and impurity control. These have yet to be overcome, although some progress has been made. Still other work under way at Wisconsin, under the direction of nuclear engineer Forsen, is the attempt to devise a method of converting the rotating system into a plasma gun, which might offer easier gyromotion conversion and effect impurity control.
Clinical fluorometry grows Changes in fluorescence caused by enzyme systems are finding use in clinical laboratories. The diminishing of the native fluorescence of nicotinamide adenine dinucleotide (NAD) from its reduced form (NADH) has been used as a basis for assaying serum lactic acid dehydrogenase and other enzyme systems, according to Dr. Martin Rubin, director of the clinical chemistry laboratory at Georgetown FEB.
13, 1967 C&EN 9
University, in a seminar on fluorescence chemistry at the University of Maryland. Advances in low-level biochemical detection are being achieved by combining the sensitivity of fluorometric assay with the selectivity of enzymic reactions. This type of analysis may be used for some nonfluorescent compounds by converting them to fluorescent derivatives using certain enzymes (C&EN, Feb. 6, page 58). Protein structures may be studied by forming fluorescent conjugates, such as via dansyl (1-dimethylaminonaphthalene-5-sulfonyl) labeling of several amino acids in the chain. Protein tracers—fluorescein isocyanate, for example—are also finding use in clinical research as biological probes. They have the advantage over radioactive labels because they can be optically traced. A procedure of particular importance in the clinical laboratory, Dr. Rubin says, is the assay of ammonia and urea using the fluorometric traits of the NADH-NAD change. This technique does not involve distillation of ammonia. Also developed is a sensitive analysis of glucose specificity, using hexokinase, glucoses-phosphate dehydrogenase, and NADP, and recording the fluorometric change in the coenzyme involved. Standard determinations are being run on urea to 400 mg. per 100 ml.; on glucose, to 500 mg. per 100 ml.; and on lactic acid, to 40 mg. per 100 ml. Dr. Rubin and his coworkers have also developed sensitive fluorometric methods for some drugs, vitamins, enzymes, and hormones which possess natural fluorescence. Compounds conveniently susceptible to fluorometric analysis include quinidine, salicylates, tetracycline antibiotics, inulin, thiamine, ascorbic acid, chelated calcium and magnesium, phenylalanine, serum proteins, cholesterol, Cortisol, catechol amines, porphyrins, lactic acid, and aspartate transaminase. The high sensitivity of fluorometry has yielded new insights. For example, aspartate transaminase enzyme in serum increases activity sharply in high dilutions. The clinical meaning of this finding for medical diagnosis is under study, says the Georgetown scientist.
New anti-inflammatory agents The s form of the dextrorotatory isomer of a chloro-substituted cyclohexylphenylacetic acid is more active than other known nonsteroidal antiinflammatory agents, according to Dr. T. Y. Shen of Merck Sharp and Dohme Research Laboratories, Rahway, N.J. The anti-inflammatory activity 10 C&EN FEB. 13, 1967
p-Biphenylylacetic acids Greater than phenoxyacetic acids
p-Cyclohexylphenylacetic acids Highest antiswelling with methyl
Ibufenac From England
of nonsteroids, like the activity of the auxins (plant igrowth hormones), is related to the stereospecificity of the molecule's asymmetric carbon atom, Dr. Shen told last week's ACS Second Middle Atlantic Regional Meeting, held in New York City. (See pages 15, 43, and 44 for additional coverage of the meeting.) In both classes of compounds, it is the s form of the dextrorotatory isomer that is most active. The compound that's the most active anti-inflammatory agent to date is ra-chloro-p-cyclohexyl-a-tfnethyrphenylacetic acid, Dr. Shen and 11 Merck coworkers have found. Several years ago, Merck scientists found that indomethacin, chemically 1- (p-chlorobenzoyl) -5methoxy-2-methylindole-3-acetic acid, and its carbocyclic isosteres, the 1arylidenyl-3-indenyl acetic acids, have potent analgesic (pain killing), antiinflammatory (swelling reducing), and antipyretic (fever reducing) activities. This prompted them to study other types of aryl-substituted acetic acids. Since then, clinical studies of ibufe-
nac, p-isobutylphenylacetic acid, by scientists at Boot's Pure Drug Co. (England) and namoxyrate, dimethylaminoethanol p-biphenyl-a-butyrate by workers at Warner-Lambert Co. (Morris Plains, N.J.) have been made. Several other acrylacetic acids have also been tested for anti-inflammatory activity by other scientists, Dr. Shen notes. The Merck Sharp and Dohme team has studied the anti-inflammatory activity of members of two families of phenylacetic acid compounds. They are the p-biphenylylacetic acids and the p-cyclohexylphenylacetic acids. Many members of these two families of compounds are highly potent antiinflammatory agents, the team finds. In addition, many of the compounds have analgesic and antipyretic activities. The p-biphenylylacetic acids have been tested on rats by Dr. Charles A. Winter and his associates at the Merck Sharp and Dohme laboratories in West Point, Pa. These compounds are much more active anti-inflammatory agents than are the corresponding phenoxyacetic acids, they find. When both benzene rings are unsubstituted (X and Y equals H ) , the activity-enhancing property of the group in the alpha position is: methyl group greater than hydrogen, and methylene greater than ethyl and higher alkyl substituents. The p-cyclohexylphenylacetic acids also have anti-inflammatory activity, Dr. Winter and his group find. As with the ip-biphenylylacetic acids, highest antiswelling activity in rats occurs when there is a methyl group in the alpha position. Less active compounds result when methylene, ethyl, or higher alkyls are substituted in the alpha position. The cyclohexyl group's enhancement of anti-inflammatory activity is highly specific, Dr. Shen says. p-Cyclohexylphenyl-a-propionic acid is about 10 times more active than ibufenac in reducing foot edema in rats, he points out. The corresponding cyclopentyl, cycloheptyl, and 2-norbornyl analogs are less effective, he notes. The activity is further increased by substitution in the benzene ring. For example, Dr. Shen and his coworkers have synthesized the ra-chloro derivative and have resolved it into its optically active isomers through its cinchonidine salt. When tested on rats by Dr. Winter and his group, the s form of the dextrorotatory isomer was found to be more active than other known antiinflammatory agents. It's thus clear that these compounds are an important new class of nonsteroidal anti-inflammatory agents, Dr. Shen says.
