Tritiated compounds

The small synthetic scale used for production of many labeled compounds creates special challenges for product purification. Eirst, because of the need for use of micro or semimicro synthetic procedures, the yield of many labeled products such as high specific activity tritiated compounds is often low. In addition, under such conditions, side reactions can generate the buildup of impurities, many of which have chemical and physical properties similar to the product of interest. Also, losses are often encountered in simply handling the small amounts of materials in a synthetic mixture. As a consequence of these considerations, along with the variety of tracer chemicals of interest, numerous separation techniques are used in purifying labeled compounds. 

Decay products of the principal radionuclides used in tracer technology (see Table 1) are not themselves radioactive. Therefore, the primary decomposition events of isotopes in molecules labeled with only one radionuclide / molecule result in unlabeled impurities at a rate proportional to the half-life of the isotope. Eor and H, impurities arising from the decay process are in relatively small amounts. Eor the shorter half-life isotopes the relative amounts of these impurities caused by primary decomposition are larger, but usually not problematic because they are not radioactive and do not interfere with the application of the tracer compounds. Eor multilabeled tritiated compounds the rate of accumulation of labeled impurities owing to tritium decay can be significant. This increases with the number of radioactive atoms per molecule. 

The production of tritium-labelled organic compounds was enormously facilitated by K. E. Wilz-bach s discovery in 1956 that tritium could be introduced merely by storing a compound under tritium gas for a few days or weeks the radiation induces exchange reactions between the hydrogen atoms in the compound and the tritium gas. The excess of gas is recovered for further use and the tritiated compound is purified chro-matographically. Another widely used method of... 

Direct Methods. The classical approach has been to prepare tritiated or carbon labeled analogs of the parent hydrocarbons which may then be used in animal or in vitro experiments. Tritiated compounds are generally easier to prepare, using exchange reactions on the parent hydrocarbon, than their 14C analogs and have higher specific activities. However, during the metabolism of such compounds, some of the tritium is released as tritiated water, either directly or... 

As of now no details of the synthesis of optically active tritiated compounds produced under microwave-enhanced conditions have been published. Another area of considerable interest would be the study of solvent effects on the hydrogenation of aromatic compounds using noble-metal catalysts as considerable data on the thermal reactions is available [52]. Comparison between the microwave and thermal results could then provide useful information on the role of the solvent, not readily available by other means. 

Group VIII transition metal catalyzed hydrogen exchange reactions are important in providing useful information concerning the fundamental processes of bond rupture and bond formation on catalyst surfaces. The reactions are also a convenient source of deuterated and tritiated compounds for chemical and biological research (i). 

In 1985 Allara and Nuzzo [354, 355] published the results of an extensive investigation in which adsorption took place on to an aluminium oxide layer formed on a film of aluminium deposited in vacuo on to a silicon wafer. Various carboxylic acids were dissolved in high purity hexadecane and allowed to adsorb from this solution on to the prepared aluminium oxide surface. The monolayers so formed were examined by ellipsometry and infrared spectroscopy. Contact angle measurements were made on the monolayer surfaces and radioactive labelled (tritiated) compounds were employed to study the interchange of adsorbed molecules with those in solution. Various other techniques of less immediate relevance to our present interests were also employed and reference to these two papers should be made for further particulars. Aluminium... 

Radiolabelled compounds for the histamine H3 receptor have been proven to be of great value in pharmacological and biochemical research. Some iodinated and tritiated compounds haven become standard research tools. In contrast, the development of PET or SPECT ligands has been proven to be troublesome. So far there has been no radiolabelled compound which is taken up into the brain in reasonable amounts to allow for PET or SPECT studies of the H3 receptor in the brain. The search for new radiolabelled compounds is still going on however, as is research to find out why these radiolabelled compounds do not enter the brain as opposed to their non-radiolabelled equivalents. One can detect pharmacological effects which can only be caused by central nervous system activity of these non-radiolabelled compounds. In view of the... 

The radiochemical analysis of salicylamide in plasma using the ring-labelled tritiated compound was reported by Stella et al (59) The tritiated salicylamide was synthesized by reacting cold salicylamide with trituim oxide in the presence of heptafluorobutyric acid. This procedure is effective for the analysis of salicylamide and its metabolites (the sulphate and glucuronide) in the presence of similar phenolic compounds. 

Figure 17.3 Binding experiments between tritiated compounds and RP-HPLC-purified antennal proteins. Each fraction corresponds to an aliquot of the purification. One pCi of each pheromonal compound was incubated with 20 pL of each fraction (sample buffer). The films were exposed to the...

The decay of one of the tritium atoms contained in a multilabeled alkane introduces into the system, together with a tritiated carbonium ion, a -particle with a mean energy of 5-6 keV. It is therefore conceivable that a fraction of the original tritiated compound can be destroyed by the radiation, forming labeled products which would be indistinguishable from the products of the reactions of the tritiated decay ions. 

In fact, the rate of formation of the carbonium ions from the 8-decay is simply proportional to the first power of the concentration of the tritiated compound in the system. On the other hand, the rate of formation of labeled radiolytic products varies with a higher power of the concentration of tritiated molecules which determines, in the first place, the intensity of the 3-radiation (and therefore the total rate of the radiolytic reactions), and in the second place, the probability that the radiolytic processes affect, in particular, a tritiated molecule. 

The yields of scavenging products from direct irradiation are small in terms of a macro effect, typical 0 values ranging from 0.05 to 0.30. However, tritium is radioactive and, thus, possesses great sensitivity in detection. In practice, relatively large volumes of solution can be irradiated (if necessary) and concentrated, or preparative gas chromatography can be used to isolate a pure product in quantities required for a particular chemical reaction. Isotope dilution may also be used to obtain high chemical yields of tritiated compounds. 

It has many applications as a tracer, for example, to study the movement of ground waters, and to study the al sorption of hydrogen by metals and the absorption of hydrogen on metal surfaces. Many deuterated and tritiated compounds have been synthesized and studied. Some of the important physical properties of the isotopes of hydrogen are listed in Table 8-2. 

Konishi, S. et al., Development of electrol3dic reactor for processing of gaseous tritiated compounds, Fus. Eng. Design, 39,1033, 1998. 

Tritium ( H) decays by beta emission to He with a half-life of 12.26 years. A sample of a tritiated compound has an initial activity of 0.833 Bq. Calculate the number N of tritium nuclei in the sample initially, the decay constant k, and the activity after 2.50 years. 

A very interesting ab initio study of p-decay in OHT, NHjT, and CHjT has been reported by Ikuta et al. [115]. P-decay of tritium yields (besides a neutrino particle u) the helium isotope He. Because of the relatively short half-life of tritium (12.26 years), tritiated compounds may be thought of as a convenient source of helium-containing molecular ions ... 

Tribollet, E. et al., Localization and quantitation of tritiated compounds in tissue sections with a gaseous detector of beta particles Comparison with film autoradiography, Proc. Natl. Acad. Sci., 88, 1466, 1991. 

The results show that it is possible to obtain H NMR spectra of solid tritiated compounds in a safe and routine manner. The examples chosen are... 

Both trans- and cis-a-chlorodecalin are reduced by tri-n-butyltin hydride to the same mixture of trans- and ri.v-dccalin in which the trans isomer predominates. Greene and Lowry13 note that this method is useful for reduction of tertiary halides it is particularly valuable for preparation of specifically labeled deuterated or tritiated compounds. 

Solubilization of proteins for radioactivity counting can be also effected by non-specific proteases or by chaotropic agents (guanidinium chloride). In the latter case gel slices are incubated with 1 ml of 6 M guanidinium hydrochloride at 90°C for 12 h. Then, 33% Triton X scintillation fluid is added and samples are counted. Efficiency is 12% for tritiated compounds. 

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