MEETING BRIEFS FROM PHILADELPHIA
Naphthalene derivative tames psoriasis lesions A tip from a 1972 Soviet drug symposium has led scientists at Syntex Research, Palo Alto, Calif., to synthe size a novel compound that shows promise as a treat ment for psoriasis, a common skin disorder with no known cure. The tip involved a rather unstable naphtha lene derivative that displayed antipsoriatic activity. Organ ic chemist Gordon H. Jones and his coworkers prepared numerous analogs of this compound, but all were unsuit able as drugs until they hit upon 6-chloro-1,4-diacetoxy2,3-dimethoxynaphthalene (RS 43179). In screening studies, this derivative appears to provide consistent and long-lasting clearing of the itchy, scaly, red skin lesions that often characterize psoriasis. Moreover, RS 43179 seems to have none of the potentially serious side ef fects or inconvenience of most current therapies. Syntex scientists expect to present results of clinical trials with the compound in the fall. Device aids study of heterogeneous fast reactions Fast reactions at high temperatures between gases and solids can be studied with a modified electrodynamic balance developed by R. Erik Spjut, John P. Longwell, and Adel F. Sarofim at Massachusetts Institute of Technology. Traditionally, a thermogravimetric analyzer (TGA)—a weighing balance with one end in a heated chamber—is used to measure reaction rates and extent of reaction in heterogeneous systems. The TGA records the temperature and weight of the sample as a function of time. However, TGAs are limited to large samples (several milligrams) and slow reactions (30 seconds or more). Spjut and his coworkers suspend particles 10 to 60 μπι in diameter in a chamber with three electrodes and heat the particles with a focused carbon dioxide laser to up to 4000 K. The device follows weight and temperature changes as a particle reacts under heating. Work is still in progress, but Spjut believes the device will be valuable for research on heterogeneous reactions, permitting study of reaction rates up to 1000 times faster than previously possible. Citral toxicity linked to vitamin A antagonism Experiments by Eli Seifter, professor of surgery and biochemistry at Albert Einstein College of Medicine, Bronx, N.Y., and colleagues provide strong support for the hy pothesis that the natural product, citral, is an antagonist of vitamin A. Citral, an open-chain monoterpene that gives the characteristic citrus tang to oils of lemon, orange, geranium, and lavender, is also widely used in perfumes and household products such as furniture polish. Seifter has shown that supplemental vitamin A slows the growth of breast tumor cells in mice, whereas supple mental citral stimulates the growth of the tumors. Increas ing the vitamin A content can override the effect of citral. Similarly, the effects of vitamin A in stimulating the growth of collagen, fighting off viral tumor formation, and causing rejection of transplanted tissue can all be coun
tered by citral. All of these effects are mediated through white blood cells or other mesenchymically derived cells, Seifter says. "Vitamin A contributes remarkably to the distinctiveness of many kinds of cells derived from these tissues," Seifter says. "This results in the enhancement of survival after severe insults varying from toxic chemi cals to physical injuries and also from biological invaders. Citral has opposite effects." Accordionlike porphyrin complexes formed A porphyrin analog that, like an accordion, can expand sideways to accommodate two metal atoms side by side in its macrocyclic ring has been synthesized by graduate student Francis V. Acholla and associate professor Kristin B. Mertes of the chemistry department at the University of Kansas. The synthesis was accomplished by means of a Schiff base template-assisted condensation of a 5,5'-diformylpyrromethane and 1,3-propanediamine. Complexes with two lead atoms or two copper atoms in the central cavity have been prepared, and other di amines are being investigated as bridges for the two dipyrromethane fragments. "The potential flexibility of these linkages makes this truly an accordionlike' mole cule by which metal ion interactions can be governed via judicious selection of the bridge," Mertes suggests. Bacterium removes selenium from mine wastes Selenium, which is present in levels too high to be environmentally acceptable in the water pumped out of uranium mines in the Ambrosia Lake district of New Mexico, can be removed from the water by treatment with anaerobic Clostridium bacteria, says Jim W. Kauffman of Kerr-McGee's technical center, Oklahoma City. Prelimi nary laboratory and field tests show dynamic removals of contaminants by soil-supported bacteria, he says. The effectiveness of the treatment is affected by temperature, flow rate, and the presence or absence of nutrients such as sucrose, lignosulfonate, and refining sludge. "We believe the reaction being carried out by bacteria in volves reduction of mine water selenate to insoluble red amorphous selenium metal, which is retained in the cell," Kauffman says. Chlorofluorocarbon concentrations increase Chlorofluorocarbons 11 and 12, which affect Earth's upper stratospheric ozone levels, have more than tripled in atmospheric concentration since measurements be gan in the 1970s, according to atmospheric chemistry professor F. Sherwood Rowland of the University of California, Irvine. Analyzing air samples collected worldwide since 1977, a team of Irvine research scien tists has found steadily increasing concentrations of four chemicals: the two chlorofluorocarbons, carbon tetra chloride, and methylchloroform. The increase is cause for some concern, Rowland says. He notes that esti mates of total ozone depletion have dropped in recent years. But, he says, too little is known about the effects
MEETING BRIEFS FROM PHILADELPHIA
of these chlorofluorocarbons in the lower stratosphere. Use of these chlorofluorocarbons has been banned in the U.S. and Canada but not elsewhere. Methane concentrations increase as well The University of California, Irvine, team led by atmo spheric chemistry professor F. Sherwood Rowland also has been analyzing regularly collected air samples worldwide for nearly seven years and has found an annual methane increase of 1.1% throughout Earth's troposphere, or lower atmosphere. Methane, through ab sorption of infrared radiation, contributes to the green house effect (Earth's warming) and also plays a role in the urban smog cycle. Rowland believes that methane concentrations are rising because the removal rate for the gas, through reaction with hydroxyl radicals, is slowing at a time when more is being produced. Methane is produced by cows in their digestion of cellulose and by biological action underwater in flooded paddies and swamps. "The rising methane concentration," Rowland says, "probably indicates that other organic compounds in the atmosphere are not being oxidized as fast as they were a few years ago, which would be as important as the rise in methane itself." Antihistamine doesn't cause drowsiness A new generation of antihistamines that won't cause drowsiness is being developed in the U.S. One member of this elite drug class is AHR-11325, a pyrido1,4-oxazepin-5-thione that was prepared by chemist Albert D. Cale Jr. of the pharmaceutical firm A. H. Robins. This compound shows "no sedative effects even at doses 50 times higher than its antihistamine dose," according to William J. Welstead Jr., the firm's director of chemical research. "In contrast, diphenhydramine, a well-known, commercially available antihistamine, shows significant sedative effects at its antihistamine dose." AHR-11325 significantly calms allergic reactions and cold symptoms for at least six hours at doses comparable to those of other marketed antihistamines. Welstead notes that this drug is still "in a fairly early stage of development." At least four other nonsedative antihistamines currently are undergoing clinical evaluation in the U.S., he adds. Group transfer polymerization continues Polymer chemists at Du Pont have carried out controlled synthesis by group transfer polymerization of an ABA block copolymer and of a highly unsaturated polymer that would be hard to make by other methods. Group transfer polymerization uses ketene alkyl trimethylsilyl acetals to add new monomer groups to a polymer chain by a reaction that constantly transfers the reactive trimethylsiloxy group to the growing chain end (C&EN, Sept. 5, 1983, page 27). For example, polymer chemists Dotsavi Y. Sogah, Walter R. Hertler, and Owen W. Webster reacted α,ω-diacryloyloxypolycaprolactone with methyl methacrylate, trimethylsilyl cyanide, and a cyanide salt to
give a resin with a polycaprolactone block flanked by two poly(methyl methacrylate) ones. Again, taking advan tage of the greater reactivity of acrylates in the process than methacrylates, the chemists treated ethylene acrylate methacrylate double ester with dimethylketene methyl trimethylsilyl acetal and zinc bromide to get poly(2-methacryloyloxyethyl acrylate). 1,8-bls(Borane) is a "hydride sponge" The first rigid, uncharged, bidentate Lewis acid has been made and its hydride-abstracting power demonstrated by Howard E. Katz of AT&T Bell Laboratories, Murray Hill, N.J. Katz sees 1,8-bis(dimethylboryl)naphthalene as the first of a series that may reveal the nature of host-guest complexation of anions by polydentate Lewis acids, analogous to previous investigations of cation complex ation. The steric crowding around the boron atoms also may give it uses as a strong, nonelectrophilic Lewis acid in catalysis, in the same way that chemists use 1,8-bis(dimethylamino)naphthalene as a base. Katz made the compound by reaction of 1,8-dilithionaphthalene with ethyl dimethylborinate, followed by treatment with boron trifluoride etherate. Chlral sulfate esters synthesized Syntheses of optically active 2-phenylethyl sulfates (oxygen-16, -17, and -18 atoms and a 2-phenylethoxy-160 group) have been made by chemists at Oxford University, England. Such compounds may be useful for studying enzyme-catalyzed reactions of sulfates. Senior scientist Salvatore J. Salamone, now at Hoffmann-La Roche, Nutley, N.J., described work with organic chemistry lecturer Gordon Lowe, supported by the Science & Engineering Research Council, to convert (S)-mandelic acid to (S)-phenylethanediol and the dlol with thionyl-180 chlo ride to cis- and trans-2-[180]oxo-4(S)-phenyl-1,3,2-dioxathiolane, which they separated. Oxidation of these in water-170 gave 2(R)- and 2(S>-[170,180]dioxa-4(SH)henyl1,3,2-dioxathiolane, which they hydrolyzed to the sulfate esters. 19th Century polyphenylene sulfide debunked "Allegations that poly(1,4-phenylene sulfide) originally was prepared by the reaction of benzene and sulfur with aluminum trichloride are a result of creative reading of the literature," according to senior research chemist James W. Cleary of Phillips Petroleum Co., Bartlesville, Okla. Thus Friedel and Crafts did not make the resin in 1878, nor Genvresse in 1897, as claimed in reviews published over the past 25 years. Repeating 19th century work in excess benzene, Cleary found only diphenyl sulfide, thianthrene, and phenylthiothianthrene. Running the reaction in inert 1,2,4-trichlorobenzene at 160 to 180 °C, he obtained a polymer of molecular weight 3500, but infrared spectra indicate it to be polythianthrylene sulfide. Phillips makes the right stuff today from p-dichlorobenzene and sodium sulfide.
