Astatine preparation

All isotopes of element 85, astatine, are intensely radioactive with very short half-lives (p. 795). As a consequence weighable amounts of the element or its compounds cannot be prepared and no bulk properties are known. The chemistry of the element must, of necessity, be studied by tracer techniques on extremely dilute solutions, and this introduces the risk of experimental errors and the consequent possibility of erroneous... 

Preparation of the isotopes of astatine is more difficult than with most radionuclides, as they cannot be synthesized by neutron irradiation this precludes the use of a nuclear reactor. To date, the bulk of... 

Numerous nuclear reactions have been employed to produce astatine. Three of these are particularly suited for routine preparation of the relatively long-lived isotopes with mass numbers 209, 210, and 211. The most frequently used is the ° Bi(a,xn) At (a = 1-4) reaction, in which bismuth 44, 74,120) or bismuth oxide (7,125) is bombarded by 21-to 40-MeV a-particles. The ° Bi(He, xn) At reaction can also be used to produce isotopes of astatine 152), the nuclear excitation functions (62) favor a predominant yield of ° At and °At. The routine preparation of astatine is most conveniently carried out through the ° Bi(a,xn) At nuclear reactions, from which a limited spectrum of astatine nuclides may be derived. The excitation functions for these nuclear reactions have been studied extensively (78, 89, 120). The... 

Identification and quantitation of the three main astatine isotopes, ° At, °At, and At, can be achieved by the appropriate measurement of a-, y-, or X-ray activity. X-rays and y-rays can be counted conveniently by well-type crystal counters, whereas a-counting requires that astatine samples be measured as infinitely thin or thick preparations. Astatine-211 can be measured by counting its 79- to 92-keV Po K-L,M,NX-rays, and, importantly, discriminated from At and ° At by their y-emissions (245, 1180 195, 545, and 782 keV, respectively). Identification and aspects of counting other astatine isotopes have been briefly discussed elsewhere (6,110). 

This preparative scheme leads to only 30% yield due to the side reactions between the meto-astatoaniline diazonium salt and astato-phenol, which cannot be eliminated even by continuous extraction of the product with n-heptane (167). All the astatophenols synthesized to date have been identified by either HPLC (99,104) or TLC (160,166,167). Their dissociation constants (KJ have been established from extraction experiments by measuring the relative distribution of compounds between aqueous borax buffer solutions and n-heptane as a function of acidity. On the basis of these derived values, the Hammett a-constants and hence the field (F) and resonance (R) effects have been estimated for these compounds (167) (see Table VI). The field effect for astatine was found to be considerably weaker than that for other halogens the resonance effect was similar to that for iodine (162). 

In view of the potential therapeutic applications of At vide infra) the synthesis of stable astatinated protein molecules has attracted much effort (see Table VII). Proteins labeled with At can be prepared most reliably and unambiguously via incorporation of previously prepared pora-AtC6H4COOH by an acylation reaction with protein amino groups 53, 156, 158, 159, 178). Labeling proteins by this method was first reported by Hughes et al. 69, 71). 

The nucleotide 5-astato-2-deoxyuridine has been obtained from 2-deoxyuridine in a manner similar to that described for preparing 5-astatouridine with a radiochemical yield of 85% (170). Attempts to synthesize 5-astato-2-deoxyuridine from the diazonium salt of 5-amino-2-deoxyuridine led only to a 2-3% yield of desired product, whereas 20-25% of the bound astatine was found in the form of 5-astatouracil (99,123). This was apparently due to hydrolysis of the 7V-glycosyl bond in the course of the diazotization reaction. The final product, 5-astato-2-deoxyuridine, was identified by TLC, paper electrophoresis (170), and HPLC (99,122,123). 

Astatination of the diazonium salt of 4-amino-methylene blue led to only 10% yield of 4-astato-methylene blue (VI). Alternatively, 4-astato-methylene blue was rapidly synthesized by heterogeneous nucleophilic isotopic exchange in the presence of 18-crown-6 ether at 80° C, with 4-iodo-methylene blue. The product was separated and identified by TLC yields ranged from 50 to 65% 41). Additionally, 2-astato-8-iodo-methylene blue (VII) has similarly been prepared in 60% yield from 2,8-diiodo-methylene blue 41). 

Chloroxytrifluoromethane, 26 137-139 reactions, 26 140-143 addition to alkenes, 26 145-146 oxidative addition, 26 141-145 vibrational spectra, 26 139 Chloryl cation, 18 356-359 internal force constants of, 18 359 molecular structure of, 18 358, 359 properties of, 18 357, 358 synthesis of, 18 357, 358 vibrational spectra of, 18 358, 359 Chloryl compounds, reactions of, 5 61 Chloryl fluoride, 18 347-356 chemical properties of, 18 353-356 fluoride complexes of, 5 59 molecular structure of, 18 349-352 physical properties of, 18 352, 353 preparation, 5 55-57 and reactions, 27 176 properties of, 5 48 reactions, 5 58-61, 18 356 synthesis of, 18 347-349 thermal decomposition of, 18 354, 355 vapor pressures, 5 57, 18 353 vibrational spectra of, 18 349-352 Chloryl ion, 9 277 Cholegobin, 46 529 Cholesterol, astatination, 31 7 Cholorofluorphosphine, 13 378-380 h CHjPRj complexes, osmium, 37 274 Chromatium, HiPIP sequence, 38 249 Chromatium vinosum HiPIP, 38 108, 133 Fe4S4 + core, 33 60 Chromato complexes, osmium, 37 287... 

Radon-211, in preparation of astatine, 31 49 Radon-226, neutron bombardment, 31 16 Rain... 

D. R. Corson, K. R. Mackenzie, and E. G. Segre prepare element 85 (astatine) by bombarding bismuth with helions. W. Minder and Hulubei and Cauchois independently give evidence for the existence of element 85 in the decay products of radon. 

J Since the most stable isotope of astatine has a half-life or only 8.3 hours, Ihc chemistry of this halogen has not been studied extensively. In Ihc following discussion generalities made eboul ihc hnlogens may or may not include astatine. In ihe present instance AlBr and AtCI have been prepared. Sec the discussion of nsiaimc chemistry later in this chapter. 

Astatine Astatine, like francium in group 1 A, is a radioactive element that occurs only in minute amounts in nature. No more than about 5 X 10-8 g has ever been prepared at one time, and little is known about its chemistry. 

The decade that has elapsed since the previous survey on the organic chemistry of astatine was published in this series1 has seen a considerable increase of knowledge. The most important results that have been achieved are those concerning the preparation and identification of astatine-labelled organic compounds utilizable for biomedical purposes and those from studying their chemical and biochemical properties. Much less has been... 

Astatination by means of nucleophilic halogen exchange, occasionally with the help of catalysts, and electrophilic replacement via demetalation seem to have become the preferred techniques. Short synthesis and separation time together with the possibility of carrier-free preparation of labelled compounds are especially important factors, bearing in mind the short half-life of astatine isotopes and the requirement of high specific activity for chemical and biomedical investigations. 

The most thorough investigation in this area was that of Harrison and Royle43 on astatination of rabbit immunoglobulin (IgG) which could be used in animal experiments. PAtBA was produced with > 90% radiochemical yield, and a reproducible overall yield of > 30% for labelled protein was obtained with negligible deastatination of the latter in vivo. These favourable results could be achieved most probably due to the fact that the PAtBA was prepared without an iodine carrier and that the micro amounts of the product were purified from the macro amounts of contaminates by HPLC. To bind PAtBA to the protein, acylation with mixed anhydride was used. Preparation of the mixed anhydride 7 (equation 5) could be carried out in about 20 minutes at ca 0 °C. For astatination rabbit IgG protein is dissolved in borate buffer (pH = 9.3) and then added to 7 (see equation 6) the procedure takes about 1 hour at ca 15 °C. The astatinated protein is separated from non-conjugated materials by gel filtration and eluted from the column by phosphate-buffered saline. 

The electrophilic character of astatine in aqueous acidic solution has been taken advantage of to prepare carrier-free astatotyrosine (10), an important compound for biomedical investigations53. An optimal yield of ca 90% was obtained if an aqueous solution of astatine together with tyrosine was dissolved in a mixture of perchloric and acetic acid and heated in sealed ampoules to 150-160 °C for about 30 minutes. Raising the temperature to... 

Chloromercury derivatives of aromatic compounds can be prepared by a number of indirect reaction routes, thereby allowing astatination via demercuration of a wide variety of compounds under mild experimental conditions. 

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