THE C H E M I C A L W O R L D THIS WEEK
ACS President Ernest Volwiler, Abbott Laboratories, who spoke at the evening meeting, with John J. Cavanaugh, C.S.C., president of the University of Notre Dame; and Kenneth Campbell, Notre Dame, chairman of the Medicinal Symposium
ACTH Claimed Yet Too Impure for Structure to Be Proved C&EN REPORTS: Second National Medicinal Chemistry Symposium NOTRE DAME, IND.-Research workers are making progress in their approach to the elucidation of the structure of ACTII, or adrenocorticotropic hormone, but much better purification must be achieved and the molecule must be better understood before chemical structure studies can be carried out properly, Ε. Ε. Hays, Armour & Co., told participants in the Second National Medicinal Chemistry Symposium of the ACS, hold here June 15 to 17. Re sults have been obtained which indicate that the active moiety of ACTII is of greater molecular weight than any of the peptides reported found in studies of its structure, but there are also indications that there is only a small percentage of ACTII in the materials which have been studied, said Dr. Hays. In support of his statements, Dr. Hays pointed to experimental work by which Armour & Co. has recently produced ACTH concentrates with a potency about 180 times that of the standard, designated in 1945 as LAI A. Obviously, it was declared, this standard is by no means pure ACTH. In discussing some of the criteria which have been used in charac terizing ACTH, Dr. Hays noted that di alysis has served as a criterion for molec ular size; yet, ACTH, which has been shown acid-stable by the Merck group and does not dialyzc under neutral conditions, will dialyze at pi I 4. He recalled state ments made that ACTII might be nitro gen-free, as activity has been found in material from which all protein was claimed to have been precipitated with 2272
trichloroacetic acid. But, h-·· declared, it has been shown that proteins are not pre cipitated quantitatively with trichloroacetic acid. Fractionation by means of pi I changes has yielded materials varying in potency, Dr. Hays reported, with the highest activity found in samples with high nitrogen content and high optical density. Dr. Hays, who was scheduled to lead the discussion on this topic, spoke in the place originally scheduled for C. H. Lu University of California, who sent his re grets the previous day because of illness. While Dr. Li did not furnish a manuscript, his abstract reported demonstration that the ACTH peptides contain an average of 8 amino acids and have an average? molecular weight of 1,200. It was re ported shown that the molecule has only o n e polypeptide chain with alanine as an end group. Dr. Li's abstract stated that it has been confirmed that t h e free amino group i s essential for adrenocorticotropic activity. Certain physicochemical data for ACTH were reported, including a molecular weight of 20,000, a cystine content o f 7.19%, and a methionine content o f 1.93%; 15.65% nitrogen and 2.30% sulfur were also reported. The chemistry of cortisone was dis cussed by H. L. Mason, Mayo Foundation, w h o described a complete method for t h e partial synthesis of cortisone from desoxycholic acid. This included introduc tion of the· 11-oxv'gen atom through a 3,9epoxy structure, as devised by Kenoall,
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Mattox, McCuckin, a n d Turner; degrada tion of the side chain and introduction of a C-21 acetoxy group by the method of Miescher and associates; introduction of the 17-hydroxyl group by Starctt's method; and the introduction of the Λ'-double bond by the procedure of Mattox and Kendall. The use of diiodofluorcscin containing iodine 131 in the location of brain tumors was o n e of the important applications of radioisotopes in medical use described by I). L. Tab'*rn, Abbott Laboratories. A method of preparation of the pure com pound has been devised. A solution con taining 1 to 1.2 inc. of iodine 131 activityis given intravenously. "Counts" from the brain area are taken at some 30 prede termined locations around the skull with in 15 minutes to two hours, during which time t h e y arc most significant. Concentration in a diseased brain is higher than in a normal brain, probably because of edema, w i t h a differential be tween corresponding areas on opposite sides being 80 t o 2 0 0 counts per minute. Workers at I lines Veterans Hospital. Chicago, have stated that the position and size o f a tumor can he definitely defined and a n estimate can b e made of its malig nancy, Dr. Tabern stated. The possible use o f gallium, a bone-seeking element, in hone tumor is now being investigated, he reported, but diagnostic and therapeutic possibilities have yet to he evaluated. In an extensive report, Dr. Tabern also dealt with other diagnostic methods, tumor therapy, studies of drug metabolism, and a number of other topics. Four obstacles to the use of isotopes in chemistry, phar macy, and medicine are being removed, l i e s a i d research workers are losing their fear of isotopes; a well trained group of "isotopologists" is gradually being built up; "basic data, methods, and equipment arc b e i n g built up; and the availability of tagged compounds, reagents, and "research medicinals" of purity and finality equal or superior to ordinary drugs is becoming established. Cardiac Drugs One of the features of the symposium was a talk on the cardiac glycosides by Arthur Stoll, of Sandoz Pharmaceuticals, Basle, Switzerland. Dr. Stoll reported on work on the splitting of the sugars from the glycosides to leave the aglycones. En zymatic splitting h a s achieved a clean, complete removal of the sugar. Activity of the glycosides was usually reduced by splitting off the sugar. An exception was found in scillirosidin, from red squill. The effect of the sugar was accounted for by crediting it with fixative power to the heart muscle. All of the sugar found in these glycosides, he said, are desoxy sugars, except D-glucose, w h i l e with the exception of i>-glucose, L-rhamnose, and D-fucose, none are found in . ources other than the cardiac glycosides. Ir. speaking of struc ture. Dr. Stoll said that the geometric con figuration of ihe lacttme ring in the agly·
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NGlNEERING
NEWS
THE CHEMICAL WORLD THIS WEEK roue.v lias been shown related to the activity. All of the active materials have a i'is configuration, while those with a trans or alio form are inactive. The analogs of Chloromycetin were dealt with by Hairy Crookes, Parke, Davis and Co. He presented a progress report on the studies ot some of the compounds related to Chloromycetin which have been studied with the hope ot finding simpler compounds w i t h equivalent activity or some related compounds with even broader activity. Nothing was reported which could be considered to be competitive, over the broad bacteriological screen with antibiotics as n o w produced. \V. K. Taylor, University of Illinois, described work in which it is being shown definitely that streptothricin, which was once considered possibly related to streptomycin, is of quite a different nature from that compound. Present evidence indicates a lack of any of the* known alpha-ainino acids, or perhaps ot any alpha-ainino acids. In his talk on the chemistry of drugs reducing skeletal muscle tone. D. S. Tarbell, University of Rochester, dealt mostly with the curare drugs. Particular interest was shown in calabash curare, which, has strong potentialities of importance both chemically and pharmaceutically. In the discussion of cardiac drugs, considerable attention was devoted to khellin, the ancient Egyptian remedy which is now being brought into use in this country. While the material produces relief of angina in a lashion similar to that of nitroglycerine, its effect lasts much longer. T h e Needle in the Haystack T h e part played by luck or chance in chemical research and the importance of alertness to see the value of phenomena which appear by chance w a s the subject of the Thursday evening address before the symposium by E. 11. Yolwiler of Abbott Laboratories, President of the ACS. Many illustrations were cited in which great discoveries were realized by tinunpredictable and unexpected appearance of the dmonstration of certain important principles. Pasteur, Perk in. Becquerel, Roentgen, and Goodyear were some w h o were shown to have benefited by their understanding of results which came about through accidents or chance.
Corp. has been licensed to manufacture and distribute SR 406 in the United States. Foreign distribution will be handled by affiliates of Jersey Standard abroad. SR 406—S fur Standard, R for R u t g e r s thus far has been found effective against most fungus diseases o f plants including garden, fruit, a n d flower crops. In 1949 SR 4 0 6 was m a d e available for testing to the U. S. Department of Agriculture and to state agricultural agencies. Several hundred pounds were shipped to Europe for experiments arranged by foreign affiliates of Standard Oil Co. ( X . J.).
Gulf Chemical Operating T h e Gulf Chemical C o . , Houston, which was shut down last year ( IÙEC Reports, January 1950) h a s resumed partial operation. At present it is producing only d e Huorinated rock phosphate ( 9 0 to 9 5 % soluble tricalcium phosphate), as a mineral supplement for cattle feed. Defluorination, accomplished by calcination of the acidulated rock, results in a maximum fluorine content o f 0.08 C^
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Members of the General Hurricane Preparation Committee evaluate hur ricane information before making decision as to the necessity for shutdown: R. W. Loomis, N. D. Griswold, H. G. Roebke, A. P. Beutel, vice president and general man ager of the Texas Division; J. R. Stein, H. D. Sherbrook, A. T. Deere, chairman of the committee, and L. E. Evans; members not present are O. E. Beutel and W. E. Roush. In the 1949 shutdown, the radar scope showed the hurricane center 190 miles from Freeport at 1,12 P.M., Oct. 3. Dow warning system had already bee™ acdvated, and preliminary tie-downs had begun. Shutdown decision wïs made when sec >e (above) showed center of hurricane 130 miles away
HURRICANE
Gulf of a new antenna dome (see on map a b o v e ) , , become a permanent installation at Dow t Chemical Co.'s Freeport, Tex., p l a n t / Army, Navy, t ! . S. Weather Bureau, and Dow research pins actual operating experience have shown that radar is accn «, rate and reliable in locating and tracking ^ Λ* tropical storms of severe and hurricane intensity within a range of 200 miles. »;.: When hurricanes are located in t h e ^ , Gulf of Mexico, U. S. Weather Bureau èx- ' ' perts and Dow's consulting meteorologist anterpi et rada observations, barometric readings, and other phenomem From its interpretations the Weather Bureau advises Do^ and the general public as to the location of the ston center and the probable area oxer which it will pass inlanc From the evaluation of hurricane information by D o w Texas Division operating board and the chairman ot tn General Hurricane Preparation Committee t h e decision ε to the necessity to shut d o w n Texas Division plants is mad bv Dow management. A definite timetable for shutdown provided, based on orders issued 12 and 6 hours, respe< tively, before actual evacuation. Glycol units, magnesiui cells and a c i d furnaces, for instance, are kept in rull oper; tion at the time of the six-hour order. Some units must m stop-the l i m e kilns are kept hot and turning at all costscasoline engine stands bv to provide power should electr current fail. Air pressure is kept up at all times, and g is maintained in most lines. When shutdown is completed, all employees except skeleton force are allowed to g o home. Special train ai bus services are provided and spot announcements issm bv Dow concerning plant conditions are broadcast at intc vais over radio stations at Houston, B a y City, San Anton: Dallas, and Fort Worth. Contact offices s e t u p m Rose berg Brenham, Bellville, and Houston by on-duty ei ployees, provide storm information and return to wor orders to evacuated personnel. Following the trail blazed by D o w in hurricane prepa: tion, industrial plants along t h e coast from Port Isab Tex to Buras, La., are forming a radio system— 1 he ^ Industries Weather Network. When this network is co pleted U. S. Weather Bureau T e l e t y p e advisories, radar < servations, and barometric recordings can b e more wid broadcast to give better hurricane warning.
sleutl ot sleuth R AnAK-hnrricane Coast-has, with the completion
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L PRESENTATION
Above. H u r r i c a n e s w e p t waves p o u n d intake at P l a n t A. Right. Closing the flood gates is a n i m p o r t a n t s t e p in hurricane preparation since t h e tides sometimes reach a h e i g h t of 12 ft.
Above. T h e h u r r i c a n e flags w e r e flying in d o w n t o w n F r e e p o r t as p l a n t s h u t d o w n started a n d chlorine prod u c t i o n was c u t , r e d u c i n g considerably the supply to carbon t e t r a c h l o r i d e a n d methyl chloride units
Plant s t o p p a g e w a s c o m p l e t e d with t h e s h u t d o w n of the light hydrocarbons unit. T h e Oct. 3 h u r r i c a n e center was then a p p r o x i m a t e l y 90 miles a w a y and t h e r a p i d a p p r o a c h ( 2 0 m.p.h. ) of t h e s t o r m , accompanied by heavy squalls, made s h u t d o w n operations a b i t hectic
Right. T h e h u r r i c a n e flags w e r e still flying o n the morni n g of O c t . 4. Above. Comp a r a t i v e l y little d a m a g e was d o n e a n d most of that to t e l e p h o n e a n d p o w e r lines
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Left. D o w radar, r o w in its p e r m a n e n t home, is more strategically located than previously. M o u n t e d 107 feet a b o v e sea level an almost completely open view of both t h e Gulf and s u r r o u n d i n g land areas is afforded. Sensitivity has b e e n greatly increased, and m o r e instruments h a v e b e e n a d d e d . T h r e e 12-inch scopes will be used: one for a c t u a l tracking, one for experimentation, a n d one for c o n t i n u o u s moving picture records during storms. R a d a r is now a highly esteemed g u a r d i a n of the Gulf Coast V O L U M E
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T h e free - flow iu«r p r o p e r t y of C o m m e r c i a l Solvents* II. Y is extremely important to manu· facturcrs of livestock ami poultry fceils. This
