Radioactive Phosphorus Compounds

The radioactive isotope P has found much use in medicine and biology (Chapter 13.5). The Sm and Ho complexes of (12.142a) above can be used in targeted radionuclide therapy. 

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This compound has been prepared by Schrader and by Pest Control, Ltd. Its translocation in the plant has been studied using the compound containing radioactive phosphorus. Compound (XX) is further discussed on p. 172. 

The chemistry of sulfur is a broad area that includes such chemicals as sulfuric acid (the compound prepared in the largest quantity) as well as unusual compounds containing nitrogen, phosphorus, and halogens. Although there is an extensive chemistry of selenium and tellurium, much of it follows logically from the chemistry of sulfur if allowance is made for the more metallic character of the heavier elements. All isotopes of polonium are radioactive, and compounds of the element are not items of commerce or great use. Therefore, the chemistry of sulfur will be presented in more detail. 

When compound (VII) was heated to 130° for 2-5 hr. it isomerized to OO -diethyl S-ethylmercaptoethyl phosphoro-thiolate (VIII). This was shown by successive partitioning of the heated product between suitable solvents, the partition ratios of the radioactive phosphorus being determined after each extraction. If only one compound is present all the ratios would be the same if two or more compounds are present, the observed over-all partition ratios would change in systematic fashion. 

If a radioisotope is substituted for a nonradioactive isotope of the same element in a chemical reaction, aU compounds formed from that element in a series of steps will also be radioactive. That makes it possible to follow the reaction pathway using instruments that can detect radiation. In this way, the series of steps involved in many important reactions has been studied, as shown in Figure 21.17. Tracers containing radioactive phosphorus-32 have also been used in biochemical research to help clarify complicated metabolic pathways. Tracers are also used to test structural weaknesses in mechanical equipment and to follow the pathways taken by pollutants. 

A scientist added phosphate labeled with radioactive phosphorus ( P) to a bacterial culture growing anaerobically (without O2). She then purified all the compounds produced during glycolysis. Look carefully at the steps of the pathway. Predict which of the intermediates of the pathway would be the first one to contain radioactive phosphate. On which carbon of this compound would you expect to find the radioactive phosphate ... 

One form of radiation therapy is isotope therapy, in which a labeled substance that is known to accumulate in the defective organ is introduced into the body. The radiopharmaceutical may be a compound labeled with radioactivity or a radioactive isotope that has the tendency to accumulate. The most-used application of isotope therapy is the use of radioactive iodine I to treat hyperthyroidism and cancer of the thyroid. The rest of the treatments are covered by treatment of blood illnesses with compounds containing radioactive phosphorus or the treatment of joints with the yttrium isotope... 

An increased sensitivity of detection can often be obtained by concentration of the total phosphorus content after irradiation bnt before measurement of the P content. In some analyses requiring the detection of very small concentrations of phosphorus, the addition, after irradiation, of a carrier material may also be incorporated in the procedure. This might he in the form of a (measured) quantity of the original P compound, since after irradiation only the P content is measured. The reason for using the carrier is that, with very low concentrations, a significant proportion of the phosphorus compound (both isotopes) may be lost in the analysis process, as, for example, by absorption on glassware. The added carrier prevents disproportionate loss of the radioactive atoms, whose concentration has to be measured. 

The effect of insulin on phosphorus metabolism in muscle was studied in three ways the incorporation of radioactive phosphorus in various phosphorylated compounds, balance studies in isolated diaphragms in which inorganic total phosphorus and labile phosphorus were measured as well as the rate of glycogen synthesis, and in vitro phosphorylation studies of creatine. 

A sample of a phosphorus compound contains phosphorus-32. This sample of radioactive isotope is decaying at the rate of 6.0 X 10 disintegrations per second. How many grams of are in the sample The half-life of P is 14.3 d. 

Glycerophosphate and phosphoryl ethanolamine containing were prepared by Chaikoff et al, (32), and their incorporation into phosphatides of liver and kidney was demonstrated by surviving slices and also in the intact animal. These experiments gave no proof that breakdown of these labeled compounds to inorganic phosphate did not occur before conversion of the radioactive phosphorus to phosphatide. 

Also present in the first test tube is a synthetic analog of ATP in which both the 2 and 3 hydroxyl groups have been replaced by hydrogens This compound is called 2 3 dideoxyadenosme triphosphate (ddATP) Similarly ddTTP is added to the second tube ddGTP to the third and ddCTP to the fourth Each tube also contains a primer The primer is a short section of the complementary DNA strand which has been labeled with a radioactive isotope of phosphorus ( P) When the electrophoresis gel is examined at the end of the experiment the positions of the DNAs formed by chain extension of the primer are located by a technique called autoradiography which detects the particles emitted by the P isotope... 

Radioactive isotopes provide a very convenient way of monitoring the fate or metabolism of compounds that contain the isotopes. When used in this way, the isotope is described as a tracer and compounds into which the radioactive atom has been introduced are said to be labelled or tagged. The labelled molecules need only comprise a very small proportion of the total amount of the unlabelled radioactive substance because they act in the same way as the non-radioactive substance but can be detected very much more easily. The varied applications of tracers in biochemistry range from studies of metabolism in whole animals or isolated organs to sensitive quantitative analytical techniques, such as radioimmunoassay. Phosphorus-32 is used in work with nucleic acids, particularly in DNA sequencing and hybridization techniques. In these instances the isotope is used as a means of visualizing DNA separations by autoradiographic techniques. 

Selected entries from Methods in Enzymology [vol, page(s)] Types of organophosphorus inhibitors, 11,686-688 toxicity hazards, 11,688 purity and analysis, 11,688 solutions of organophosphorus compounds, 11,689 estimation of specific radioactivity of organophosphorus compounds, 11,689-690 method for estimating phosphorus content, 11,691 reactions with enzymes, 11,691 -701 [rate constants, 11,692 phosphorylation of chymotrypsin, 11, 694-696 identification of phosphoryl and phosphonyl peptides,... 

Lee et al. (1975) also qualitatively studied urinary metabolites of32P-labeled white phosphorus in rats. They used thin-layer chromatography (TLC) at 4 and 24 hours after a single oral dose to show that radioactive urinary metabolites consisted of two classes of compounds. One of the compounds corresponded to inorganic phosphate, the other compound was less polar and suggested an organic phosphate, although the composition of this class of metabolites was not determined. TLC analysis of liver extract also showed two classes of compounds with similar properties. 

In 1960, Hewitt and Notton estimated the phosphorus in fractions of tomato and cauliflower leaves using 32P coupled with extractions. Bowen et al. (1962) fed tomato plants with a number of radioactive elements, the fresh tissues were then extracted with a series of extractants. The results posed a number of interesting questions, for example, the association of cobalt and iron with proteins, and the authors suggested that a high speed centrifuge should be used to separate intracellular particles of different sizes. The nature of the metal compounds extracted was also questioned. Some inconclusive paper chromatography was also reported. 

The real application of this process is the recalcination of lime sludges from water treatment plants, coking of heavy residues and tars from petroleum refinery operations, concentration and volume reduction of liquid, radioactive wastes, and treatment of refinery sludges containing hydrocarbons, phosphorus, and compounds of calcium, magnesium, iron, and aluminum. 

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