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olution MS and the newer multiple and hyphenated ... “We need more and more information as the mol- ... assurance information ... F. Science 1987,23...
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FOCUS olution MS and the newer multiple and hyphenated MS techniques. "We need more and more information as the mol­ ecule gets larger," said McLafferty. However, "if you are going to get 106 pieces of data, it is not certain that it will distinguish isomers. We have never shown these problems to outsiders," McLafferty admitted. To illustrate the point, McLafferty presented a host of spectra showing different fragmenta­ tion patterns for the same molecule run under slightly different conditions, or slight changes in structure (e.g., a shift of a double bond) producing very dis­ similar patterns. Fortunately, solutions to these prob­ lems are now appearing. New tech­ niques such as tandem MS, ion-mole­ cule reactions, or photodissociation of­ fer sophisticated ways to acquire mass data on molecules as large as 100,000 daltons. One of the new MS techniques was discussed by the winner of the ACS Award for Nuclear Chemistry. Ronald Macfarlane, from Texas A & M Univer­ sity, recounted how 262Cf particle desorption mass spectrometry (PDMS) evolved from a technique to identify short-lived radionuclides produced from nuclear reactions. Spectra from time-of-flight MS revealed a persistent impurity peak in the radionuclide ex­ periments. Macfarlane determined that the impurity came from a surface collecting radioactive atoms. In tracking down the impurity, Mac­ farlane discovered that β decay using a source like 252Cf could desorb surface molecules under high vacuum from a matrix. More importantly, the mole­ cules were ejected with low internal ex­ citation, allowing Macfarlane to gener­ ate molecular ions for large, nonvola­ tile, and fragile molecules such as proteins. Although other desorption techniques, such as fast atom bom­ bardment, have been developed, Mac­ farlane says t h a t 252 Cf-PDMS " r e ­ mains as one of the most powerful MS methods, particularly for the analysis of proteins up to 35,000 daltons." Another approach for analyzing large molecules was presented by Pur­ due University's Fred Régnier, winner of the ACS Award in Chromatography. "In proteins with as many as 500 amino acids, what are the discrimination limits?" asked Régnier. This is an important question for biotechnology firms looking for ways to assess errors—some quite small—that are regularly found in proteins manufactured by genetically engineered organisms. Regnier's group has been investigating how well techniques such as ionexchange and reversed-phase chromatography distinguish these errant pro-

teins. T h e protein's bulky threedimensional shape limits the number of molecular sites that can interact with the chromatographic sorbent. Yet Regnier's group has succeeded in separating proteins that vary by only a methylene group. They find that the interacting site— whether a charged amino acid or a histidine residue—is affected by its local microenvironment (3). For instance, variations in the amino acid that sits 15 À from a histidine on the protein serine protease subtilisin produced significant changes in retention time on an immobilized metal affinity column. In total, the microenvironment covered ~600 À2 of protein surface. Régnier points out that chromatography could deliver in minutes quality assurance information that now takes a full day to collect. By obtaining timely information, manufacturers could correct production problems in midstream. Another problem of the biotechnology industry was tackled by University of Maryland microbiologist Rita Colwell. Speaking at the Division of Environmental Chemistry, Colwell challenged chemists to find new ways to track genetically altered organisms released into the environment, warning that "recall is not possible." Anything released "must be detectable," she said. Analysis is required to answer questions about the organism's persistence in the environment and its gene transferability from altered to wild forms. Pathogenicity, according to Colwell, is "highly unlikely," especially because modified organisms lack the genes to invade a host. Measurements must detect a single gene or 1-2 cells in a given volume. For example, the recently developed polymerase chain reaction (PCR), functioning like a Xerox machine to reproduce multiple copies of a DNA fragment, allows the detection of one gene copy per gram of soil. The full meeting schedule left little time to explore Dallas, so the city came to the meeting. In honor of National Chemistry Week, ACS staged its first chili cook-off inside the city's elegantly restored Union Train Station. Cowboy bandanas, a country western band, and entertainment by local sections added extra zest to the taste testing. From cold fusion to chili, the meeting offered a week of Texas-sized events. Alan R. Newman References (1) Fleischmann, M.; Pons, S.; Hawkins, J. Electroanal. Chem. 1989,261, 301-08. (2) Enke, C. G.; Wade, A. P.; Palmer, P. T.; Hart, K. J. Anal. Chem. 1987,59,1363A1371A. (3) Régnier, F. Science 1987,238,319-23.