ANALYTICAL CHEMISTRY
204 Tropoelin 00 wa8 found to be more eatisfactorv than bromoDhenol
(3) Schwab. G. B., and Dattler, G., Z.angew. Chem., 50, 691 (1937);
LITERATURE CITED
(6) Ibid., p. 257. (7) I b X , p. 2?2. H. H., Liggett, L. M., and Diehl, H., IND.ENG CHEM., ~ ( 8 )~Willard, -
~ ~ iF.,~"Chemistry l , of specific, selective, and sensitive R tions," pp. 602-4, New York, Academia Press, 1949. ( 2 ) Kubli, H., Helv. Chim. Acta, 30, 453 (1947). (1)
~
ANAL.ED.,14,234 (1942).
RECEIVED June 26, 1950.
Procedure for Radiochemical Determination of Astatine in Biological Material WARREN M. GARRISON, J E A " E D. GILE, ROY D. MAXWELL', AND JOSEPH G . HAMILTON University of California, Berkeley and Son Francisco, Calif. STATIXE, the artificially produced radioactive halogen of atomic number 85, accuniulates (I, 6) in the thyroid gland in a ma,nner similar t o radioiodine. Recent ( 4 ) observations on the radiobiological properties of 7.5-hour AtZ1I show that the alpha-particles emitted in the decay of this isotope produce severe radiation damage t o thyroid tissue without apparent involvement of the adjacent parathyroids, indicating that astatine may have unique therapeutic application in hyperthyroidism. With mts, a dose of 10 pc. of At211 is sufficicnt to produce a marked degxw of injury t o the thyroid follicles. As part of a detailed study of the metabolism and radiobiology of astatine now in progiws a t this laboratory, analytical procedures have been drveloped for the determination of astatine in biological material and are nsported in the present paper. I !
maximum scnsitivity was required. Although Atz*I emits 80k.e.v. x-rays as well as alpha-particles, the low counting efficiency of the At211 x-rays made it necessary t o use alpha-counting methods, so that the required sensitivity could be attained. The experiment:illy determined alpha-particle-~-ray counting ratio was found to be approximately 850.
Table 1.
Radiochemical Analysis of Astatine in Biological Materials Tissue
(10Grams Wet Weight) Fat Bone Skin lluscle
T e method
96.0 93.5 98.5 94.0
Recovery .4g method
74.5 105.0 92.5 108.0
96.0 103.0 100.0
99.0
94.0 93.0 98.5 93.9
PREPARATION OF ASTATINE ( I , 6, 7)
Bombardment of bismuth with alpha-particles in the energy range 20 t o 29 m.e.v. produces, by (a,2n) reaction, 7.5-hour At211, free from other astatine isotopes, notably the 8.3-hour At210. Sixty per cent of the ..ltzll nuclei decays by K-electron capture, with the emission of an 80-k.e.v. x-ray to Po*11,an alphaemitter with a 10-3 second half-life, and 40% decays by alphaparticle emiesion t o form Biz''. Above 30 n1.e.v. 8.3-hour At2Iois produced by (a,3n) reaction. This isotope decays by K-electron capture t o l a d a y Po*lO and was, therefore, an undesirable radioactive contaminant in the astatine preparations described here. The bismuth was pupported on a watcr-cooled aluminum target plate 10 mils thick. A small amount of C.P. bismuth was melted on the aluminum disk, forming an aluminum- bismuth alloy which did not require flux. A bismuth layer of the desired thickness &as obtained by fusing the required amount of bismuth to the alloytd surface. The plate was mounted in a bell-jar t y e target assembly and bombarded with 30-n1.e.v. alpha-partids obtained by degrading the 40-m.e.v. beam of the 60-inch cyclotron at Clocker Laboratory. The surface of the bismuth was cooled with a stream of helium. Beam currents up to 15 pa. were used without noticeable fusion of the bismuth surface. After bombardment, the bismuth section was cut from the target foil and astatine was isolated by heating the bismuth to 425' C. in to a stream of nitrogen carrier gas a t a pressure of' mm. The astatine was collected a t liquid-air temperatures on a cold finger which had been covered with a thin layer of ice. After the bismuth had been heated for approximately 20 minutes, a solution of astatine in a minimum volume of water was obtained simply by removing the cold finger from the vacuum line and warming to room temperature. ANALYTICAL PROCEDURES
Because a 10-pc. dose of produces noticeable thyroid damage in the rat ( 4 ) ,the metabolism in normal animals had to be studied a t t,he 1- to 5-pc. dose level. Therefore, t o obtain distribution data of the desired accuracy, an analytical procedure of 1
Present address, Walter Reed Hospital, Washington, D. C.
The most satisfactory method found for oxidizing biological material prior t o astatine analysis involves the wet oxidation of tissue wit'h a mixture of perchloric and nitric acid. With this proccdure, astatine is quantitatively retained in aqueous sohtion, presumably in the highest positive oxidation state (6). The oxidation proceeds smoothly if the solution contains 10 t o 3070 nitric acid during the digestion period. After oxidation is conipletv, the nitric acid is distilled off to give a concentrated perchloric acid solution containing the astatine and other inorganic tissue constituents. The solution is then cooled and diluted with water to the desired normality for the subsequent separation. In the espcriments describcd in the present paper, the oxidation and dilution steps were routinely performed behind s a precautionary measure, although no difficulties with esplosions were encountered in over one hundred determinations. In developing procedures for the quantitative separation of At211 from gram amoimts of tissue so that alpha-particles could be counted, several coprecipitation procedures ( 2 , 2, 6) were tried. The most satisfactory of these involves the coprecipitation of astatine on elemental tellurium carrier from a 3 N perchloric acid solution following a wet oxidation of the biological material with perchloric-nitric mixture. Determination of Astatine by Coprecipitation with Tellurium. A sample of astatine-containing tissue (less than 10 grams wet weight) is placed in a 100-ml. borosilicate glass beaker and digested in a minimum volume of 9 N perchloric acid containing 30% by volume of 16 N nitric acid. -4fter the organic material has been oxidized, the clear solution is evaporated to 10 to 15 ml. of concentrated perchloric acid. The solution is cooled and diluted to 3 N , and 5 mg. of tellurium M tellurous acid are added together Rith 1 ml. of 12 N hydrochloric acid. (Tellurous acid is only slowly reduced in cold 3 S perchloric acid in the absence of dilute hydrochloric acid.) A stream of sulfur dioxide is passed through the solution, precipitating metallic tellurium which carries astatine quantitatively. The tellurium is separated by centrifugation, washed three times with distilled water, and
V O L U M E 23, NO. 1, J A N U A R Y 1 9 5 1 Table 11.
205
Rate of Astatine Deposition on Silver in 3 N Perchloric Acid Time, Min. % Deposited
dried in air, and counted for alpha-activity. Although the astatine deposits principally on the to surface of the silver foil, for quantitative results both sides of &e foil were counted for a1ph:iactivity. Typical analytical results are qhown in Tables T a n d I I. SU&lnfAHY
transferred to a porcelain counting dish. After drying a t 70' ( ' , the dish is counted for alpha-activity. Typical results f n r R series of different tissues are shown in Table I.
i i i 1)ioIokc:il I'roceciurrs for the riitliocheniic:il analysis of material are described. Organic suhstitnces can he destroyed hv perchloric acid-nitric acid digestion without lose of astatine 1 1 1 . volatilization. .istatinel may hc imlated for alpha counting froin R 3 .V pwchloric acid solution of the oxidation product, t)y miprecipitation with nietallir tc~lluriunior deposition on silvcbr foil. Both procedures may be uscd for quantitative analy,qis. Th(s silver foil method is simpler, requires less time, and is mor(. easily adapted to routine clctrrniinc+tinnsn.here large i i i i i i i t r t w of t i w i f h s are to bt. analyzvil.
The principal objection t o the tellurium coprecipitation met hod is the time required in centrifuging, washing, and transferring thc roprecipitant. To obtain a more rapid analytical procedure, other chemical properties of astatine were studied, particularly its deposition on metallic foils which may be measured for alphaactivity directly. Although astatine is chemically similar t n iodine, the lighter halogen homolog, it also shows definite metrrlllr properties. The similarity between adjacent elements in the lad rows of the periodic table is marked and astatine shows a (510sfi resemblance t o polonium in marly of its properties (1, 1,6). I k pause polonium may be quantitatively removed from dilute arid b i deposition on silver ( 3 ) , a similar study was made with aPt:itine. It n a s found that astatine in biological material may bf, quantitatively recovered by deposition on silver foil from a 3 \perchloric acid solution after organic material has been oxidizrrl bv the perchloric-nitric acid digestion.
The authors wish to thank It.. F. Leininger for his i i i a ~ t yht~1~)i'uI suggestions, Thomas Putnam, G. H. Rossi, and the crew of t,ht: 60-inch cyclotron, and 1l;tlcolm W(.hh for his assistance in dvsisning the target awenihly.
Determination of Astatine by Deposition on Silver Foil. A sample of astatine-containing tissue is digested in a mixture of perchloric-nitric acid as in the tellurium procedure. After digastion is complete, the solution is eva orated until the perchloric acid fumes (approximately 10 m l j , diluted to 3 N with the addition of distilled water, and transferred to a 50-ml. beaker A circular silver foil 2 mils thick of a size convenient for alpha counting is placed in the bottom of the beaker and the solution iz stirred for 30 minute8. The foil is washed in water and aretonc,
( 6 ) Johnson, G. L., Leinineel R . F..and Segre, E., J . Chem. I'hi/s., 17, 1 (1949). ( 7 ) Kelley, E. L., and Segre, E., Phys. Reo., 75, 999 (1949).
ACK~OU'I,F:DGJMENT
LI1'ER.ITPRE CITED (1'1 ('orson, D. R., JIacKsnzie. K. R . . and Segre, E., P h y s . Rw.. 57, 439 (1940). ( 2 ) Ibid., 58, 672 (1940). (3) Erbacher and Phillip, 2. Phys.. 51, 309 (1928). (4) Hamilton, +J. G., Asling, C . I\-.. Garrison, W. hi., Scott, K. G., and Axelrod-IIellei. I)., Prric. SOC.E z d . B i d . Med.. 73. :pi (1950). ( 5 ) Hamilton, J. G., and P n l ~ p .If. H., PTOC. XatE. Acad. S c ? . . 26, 483 (1940). I
RECEIVEDJune 26, 1950. Based on work performed under Contract
Yo
W-7405-eng-48 for the Atomic E n e r g j Commission.
40. Nitroguanidine Contributed by WALTER C. MCCRONE Arniour Research Foundation, Illinois Institute of Technology, Chicago 16, Ill. ~ X C E L L E N T crystals
of nitroguariidine can be obtained fruin
EA water by slow cooling. Crystals from a drop of water on microscope slide are usually too h e to be used. Ketones and :I
alcohols have been reported to form addition compounds with nitroguanidine, although crystallization from these solvrnts has been suggested a8 a means of obtaining equant crystals which have higher bulk dendties (3).
CRYSTAL MORPHOLOGY Crystal sytem. Orthorhombic. Form and Habit. Elongated rods sho%ing forms { 1101 rind f 301 } and when massive, 010 1. AGal Ratio. a:h:c: = 0.708: 1:0.143; 0.713: 1:0.146 (I). Interfacial Angles (Polar). 301.4 501 = 63'. Cleavage. Parallel to c. X-RAYDIFFRACTION DATA Cell Dimensions. a = 17.58 A.; b = 24.84 8.;c = 3.Fj8 .I.; n = 17.47A.; h = 21.50.2.: c = 3.59A. ( 2 ) . Principal Lines
Structural Formula of Nitroguanidine Although Bridgman reports poljmorphism for nitroguanidine at a temperature less than 150" c'. under a pressure less than j0,OOO kg. per sq. cm., thcw is no evidence of polymorphisni nt ntmospherir pressure.
d
IIIl
d
I/Il
7.139 6.172 5.579 6.074 4.390 4.144 3.584 3.221 3.081 2.985 2.920 2,732
0.03 0.02 0.01 1.00 0.10 0.80 0.65 0.02 0.02 0.02 0.60 Very n e A k
2,650 2.484 2.384 2.313 2.208 2.174 2.128 2.069 2.011
0.65 Very weak 0.70 Very weak
1.900 1.869
Very weak 0.10 0.10 0.50 0.01 0 02
