Search for chick edema factor X-ray crystallographers at Procter & Gamble's Miami Valley Laboratories, Cincinnati, Ohio, have determined the molecular structure of one of the toxic compounds known as the chick edema factor. According to Dr. Joseph S. Cantrell, single-crystal structural analysis shows that the structure is 1,2,3,7,8,9-hexachlorodibenzo-pdioxin. Dr. James C. Wootton of P&G has synthesized this compound and shown that it produces the same symptoms in chicks as the isolated material on which the structure work was done,
spectrometric and chemical analyses led to an assumption that the substance was a hexachlorinated hexahydrophenanthrene. At this point, Dr. Cantrell and his coworkers, Dr. N. C. Webb and Dr. A. J. Mabis, undertook to determine the structure by single-crystal studies. Two crystals, each about 0.2 X 0.1 X 0.1 mm. and weighing about 3 micrograms, were recrystallized from a benzene-hexane solution. X-ray diffraction data were obtained with an integrating Weissenberg camera. With such small crystals, exposure times were so long that the camera had to be
The final data show that the 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin molecules are nearly planar, and are packed in the 044 crystallographic planes, with an interplanar separation of about 3.3 A. No unusual bond lengths or angles are apparent. Dr. Cantrell, currently at Miami University in Oxford, Ohio, feels that this structure determination via crystallographic methods represents somewhat of a paradox. "The two proposed structures are geometrically similar, but quite different chemically," he says. "One would expect that the chemical and spectroscopic methods would be most powerful in distinguishing between the two. Instead, it was the single-crystal method which yielded the correct answer."
Short laser pulses measured
Crystallographers Cantrell, Mabis, and Webb Correct answer with single-crystal method
Dr. Cantrell told last week's meeting of the American Crystallographic Association, in Atlanta, Ga. Identification of the chick edema factor has been the subject of intensive work since a sporadic occurrence in specific lots of animal feed fat in 1957 brought significant losses to poultry farmers in southeastern and central U.S. Chicks afflicted with edema, or hydropericardium, suffer an accumulation of fluid in the heart sac and gross kidney and liver damage; 5 micrograms can kill a chick. Tests for the presence of the edema factor have been developed (C&EN, Nov. 21, 1966, page 53) by the Food and Drug Administration, which has responsibility for regulations in this area. P&G, a major producer of animal feed fat, undertook the structure determination even though the substance was never found in its raw materials or products. In 1961, Dr. Wootton isolated about 4 mg. of the toxic material from 100 pounds of contaminated fat obtained from trade sources. Mass spectrometric analysis showed the molecular weight to be 388 and indirect x-ray fluorescence indicated the absence of oxygen. These and other 10 C&EN JAN. 30, 1967
in helium to reduce background scattering. About 1100 reflections were recorded. Initially, the classical interatomic vector map approach was taken to analyze the data. Trial structures based on a phenanthrene model were unsuccessful, so the symbolic addition method, developed by Dr. Jerome Karle and Dr. Isabella Karle of the Naval Research Laboratory, was tried. A three-dimensional electron density map was calculated and examined in the 044 plane; this showed a large number of recognizable peaks. Some were large enough to be chlorine, and others of an intermediate size were taken to be carbons. A phenanthrene structure was fitted to this electron density map. But from subsequent calculations it became evident that the phenanthrene structure had to be abandoned in favor of an anthracene skeleton. Refinement of the data on the bridging atoms showed the electron densities to be higher than carbon. Substitution of oxygen-bridging atoms in the trial structure and additional refinement of the electron density map brought out the correct structure.
A coincidence technique for measuring the duration of a pulse of laser light as short as 4 picoseconds (4 trillionths of a second) has been developed at International Business Machines Corp. by physicist John A. Armstrong. The new technique will be useful in studying short intense laser pulses interacting with matter, IBM says. It should also have application to molecular interactions, which have reaction times comparable to these pulse times. Conventional techniques using photodetectors and traveling-wave oscilloscopes measure time intervals down to only about 400 picoseconds. There has been indirect evidence for pulses as short as a few picoseconds, but until now no technique has been fast enough to measure these directly. In the coincidence technique worked out by Dr. Armstrong [Appl. Phys. Letters, 10, 16 (1967)], the short pulses come from a phase-locked neodymium-glass laser at intervals of about 6 nanoseconds (6 billionths of a second). The laser beam is first polarized, then split into two beams. The plane of polarization of one of the beams is rotated 90%. Also, the path length of one of the beams is made adjustable with a movable prism. Both beams enter a gallium arsenide crystal. Since gallium arsenide is optically nonlinear, it can generate harmonics of the laser frequencies. But if the plane of the laser light falls along one of the mutually perpendicular axes in the crystal, the crystal produces no harmonic light. Dr. Armstrong adjusts the plane of polarization of each beam so that it aligns with an axis in the crystal. A single pulse arriving at the crystal, then, produces no harmonic light. But if the path length of one of the beams is adjusted so that two pulses arrive
