third-order nonlinearities. They have used ring-opening metathesis polymerization to convert cyclooctatetraene derivatives into substitut ed polyacetylenes. The substituents make the polymers soluble as well as amorphous, so that they don't scatter light like crystalline polyacetylene. As a result, says Grubbs, they can be fabricated into good op tical-quality films. Trade-offs often must be made. For example, of two polyacetylene derivatives Grubbs discussed in Bos ton, the more soluble one isn't the one with the higher nonlinearity. Furthermore, scientists have found that to obtain high thirdorder nonlinearities, the conjugation length must be increased. But with increasing conjugation, the polymer absorbs more wavelengths of the visible spectrum, cutting down on the wavelengths that can be used in applications. Scientists aren't sure how to get around this difficulty. According to AT&T's Sohn, cur rent approaches to designing better third-order NLO materials are "lead ing only to incremental improve ments, while a major breakthrough is needed for these materials to be come useful for device applica tions." Basically, he says, "it's not been demonstrated what you need to do to get large third-order ef fects." Part of the problem, Marder says, is that measurements of 7 are particularly complex. Also, third-or der effects involve the interaction between two excited states (unfilled orbitals) and chemists "don't have a really good grasp of how to probe or maximize such interactions." Marder believes that too many in vestigators are trying to achieve breakthrough enhancements of third-order properties and too few are doing the mundane, "nonsplashy science" that will lead to a fundamental understanding of the structure/property relationships. Making small, incremental improve ments in polymer properties will not lead to such an understanding, he says. "I think it is time to step back and learn how to control thirdorder properties in small, welldefined molecules. And then maybe we can apply this to conjugated polymers and make a quantum leap." D
Reagent determines chiral optical purity Chemists at the University of South Carolina, Columbia, have invented a selenium-containing nuclear mag netic resonance shift reagent to de termine optical purities of chiral compounds even when the dissym metric center is as far as nine atoms awayirom the selenium atom [/. Am. Chem. Soc, 112, 4979 (1990)]. The re agent may find uses among medici nal chemists seeking to satisfy com ing regulations of the Food & Drug Administration on drugs that may exist as two or more enantiomers. Chemistry professors Louis A. Silks III, R. Bruce Dunlap, and Jer ome D. Odom form amides of op tically active carboxylic acids via their acid chlorides with (4R,5S)-(+)4-methyl-5-phenyl-2-oxazolidinselone. They also react chiral alco hols or amines with phosgene or with bis(trichloromethyl) carbonate (triphosgene) to convert these to alkyl chlorocarbonates or carbamyl chlorides for coupling to the selone. The method depends upon the appearance of separate peaks in the Se NMR spectrum for each diastereoisomer of chiral substrate with the selone enantiomer. The natural abundance of 77 Se is 7.5%. The separation between peaks de creases with increasing distance be tween the selenium atom and the dissymmetric center. For example, the peak separation for the deriva tive of racemic cx-methylbutyric acid is 3.1 ppm, of β-methylcaproic acid 2.6 ppm, of 7-methylcapric acid 0.4 ppm, of δ-methylenanthic acid 0.094 ppm, and of lipoic acid (1,2-dithiolane-3-pentanoic acid) 0.019 ppm. The method also works with such aliènes as 2-terf-butylpenta-2,3-dienyl oxyacetic acid (0.175 ppm) and with α-deuterophenylacetic acid (0.071 ppm). The South Carolina investigators made the selone reagent starting with (lS,2R)-( + )-norephedrine. They protected the hydroxyl group as the terf-butyldimethylsilyl ether and converted the amino group to a formamide with formic acid. Treat ment of the formamide with phos phorus oxychloride and triethylamine converted it to an isonitrile.
Selone reveals optical purities of compounds
^-Norephedrine
Selone
TBS = ferf-Butyldimethylsilyl
The isonitrile reacted with elemen tal selenium to give an isoselenocyanate. Finally, tetrabutylammonium fluoride cleaved the silyl ether and cyclized the compound to the oxazolidinselone. Future work at South Carolina in cludes developing a way to deter mine absolute configurations of enantiomers from 77 Se NMR spec tral patterns. Stephen Stinson
Reagents selectively cleave proteins Two independent research groups, one at Yale University and one at the University of California, Berke ley, have used similar strategies to develop reagents that selectively cleave proteins. Such reagents could prove valuable for characterizing the structure and activity of pro teins, and could lead to the develop ment of new therapeutic agents. At Yale, assistant chemistry pro fessor Alanna Schepartz and gradu ate student Bernard Cuenoud target ed calmodulin, a calcium receptor protein that plays an important role in cellular regulation. They synthe sized trifluoperazine-EDTA (TFE), which consists of the iron chelator June 11, 1990 C&EN 25
€pWORKESE®cr VJUK&dilUP j^P^
At the ^ ^ N ^
^ACS National Meeting^ WASHINGTON, DC Saturday-Sunday ^August 25-26, 1990^^
An exceptional opportunity to listen to, meet, and discuss your flavor research with world-renowned scientists. WHO SHOULD ATTEND This workshop is designed to help scientists involved in food flavors. Participants should have a fundamental knowledge of organic, physical, and analytical chemistry. Registration will be limited to allow participants easy access to lecturers for discussion of specific problems. Because the workshop will fill quickly, we urge early enrollment to avoid disappointment. KEY TOPICS • •
The latest methods of isolation and characterization of flavor chemicals Recent advances in thermal and enzymatic conversion of precursors in flavor compounds • • •
Potent flavor compounds Specific odor characteristics
Biotechnology in flavor research FEE
ACS Members, $745; Nonmembers, $845 (The fee includes a course manual and a wine and cheese reception/mixer following the first day's lectures.) HOW TO REGISTER For additional information, or to register for the workshop, call or write the Department of Continuing Education, American Chemical Society, 1155 Sixteenth Street, N.W., Washington, D.C. 20036. 1-800-227-5558 or 202-872-4508. A description of the ACS national meeting will appear in the June 4 (Preliminary Program) and July 9 (Final Program) issues of Chemical and Engineering News. ACS 12 26
June 11, 1990 C&EN
Science/Technology e t h y l e n e d i a m i n e t e t r a a c e t i c acid (EDTA) covalently bound to the calmodulin antagonist trifluoperazine (TFP) [/. Am. Chem. Soc, 112, 3248 (1990)]. The chemists find that TFE binds calmodulin u n d e r physiological conditions, and in the presence of Fe 2+ and oxygen, oxidatively cleaves the protein to produce six major cleavage fragments. They show that a 10-fold excess of TFP abolishes the TFE-Fe-mediated cleavage reaction. The cleavage reagent only cleaves calmodulin that has bound four calcium ions. The Yale researchers are currently carrying out experiments to determine the precise calmodulin cleavage sites. They are also evaluating other cleaving reagents for their ability to modify proteins. At Berkeley, chemistry professor Peter G. Schultz, postdoctoral fellow Denton Hoyer, and graduate student Ho Cho targeted the protein streptavidin, a protein that binds biotin. The chemists attach EDTA to biotin, which then delivers redoxactive copper or iron to the binding sites of the protein. They synthesized two forms of biotin-EDTA, one of which couples the EDTA closely to the biotin, and one of which couples it through a seven-atom tether [/. Am. Chem. Soc, 112, 3249 (1990)]. The Berkeley chemists find that, in the presence of oxygen and Fe 3 + or Cu 2 , the biotin-EDTA reagent in which the two groups are closely linked cleaves streptavidin in a manner that suggests the cleavage reaction is occurring close to the biotin binding site of the protein. Biotin completely inhibits the cleavage reaction. According to Schultz, attachment of redox-active chelates to other ligands or to antibody combining sites may lead to a new class of affinity cleavage agents, to the design of catalytic drugs, or to the generation of a family of sequence-selective peptidases. Schultz notes that Claude F. Meares, a chemistry professor at the University of California, Davis, demonstrated earlier this year that EDTA-Fe covalently bound to a protein is capable of cleaving the protein backbone. Rudy Baum
