Isotopes primary

Isotope Primary decay mode Half-life T,/2 (years) Useful photon energies emitted % Theoretical yield (photons per 100 decay transformations) Typical activity (mCi)... 

Isotope Primary Decay Mode Half-Life (Years) Useful Photon Energies Emitted % Theoretical Yield (Photons per 100 Decay Transformaticns) Typical Activity (mCi)... 

From D- and L-threonine, the two pyridoxamine products give different isotopic primary effects with glutamic-oxaloacetic transaminase. 

It is clear, then, that the measurement of primary kinetic isotope effects will not give a wholly unambiguous clue to mechanism in the absence of other evidence. Nevertheless, the absence of a kinetic isotope effect is most easily understood in terms of the /S 2 mechanism... 

A primary isotope effect /ch/ d of 6.4 (extrapolated for 35 C) is observed for the metalation and the methylation of 171b when the C-5 position is deuterated. This value is in excellent agreement with the primary isotope effect of 6.6 reported for the metalation of thiophene (392) and it confirms that the rate-determining step is the abstraction by the base of the acidic proton. 

Because variations in accurate isotope ratio measurements typically concern only a few parts per 1000 by mass and there are no universal absolute ratios, it is necessary to define some standards. For this purpose, samples of standard substances are produced and made available at two major centers IAEA (International Atomic Energy Authority, U.K.) and NIST (National Institute for Standards and Technology, U.S.). Standards from other sources are also available. These primary standards can be used as such, or alternative standards can be employed if the primary ones are not available. However, any alternative standards need to be related accurately to the primary ones (see formulae below). For example, the material PDB (PeeDee belemnite), used particularly as a standard for the ratio of isotopes, is no longer readily available, and a new standard, VPDB,... 

Boron, in the form of boric acid, is used in the PWR primary system water to compensate for fuel consumption and to control reactor power (3). The concentration is varied over the fuel cycle. Small amounts of the isotope lithium-7 are added in the form of lithium hydroxide to increase pH and to reduce corrosion rates of primary system materials (4). Primary-side corrosion problems are much less than those encountered on the secondary side of the steam generators. 

The primary issue is to prevent groundwater from becoming radioactively contaminated. Thus, the property of concern of the long-lived radioactive species is their solubility in water. The long-lived actinides such as plutonium are metallic and insoluble even if water were to penetrate into the repository. Certain fission-product isotopes such as iodine-129 and technicium-99 are soluble, however, and therefore represent the principal although very low level hazard. Studies of Yucca Mountain, Nevada, tentatively chosen as the site for the spent fuel and high level waste repository, are underway (44). 

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. 

Generally, labeled compounds are prepared by procedures which introduce the radionuchde at a late stage of the synthesis. This allows for maximum radiochemical yields, and reduces the handling time of radioactive material. When dealing with short half-life isotopes, a primary consideration is the time required to conduct synthetic procedures and purification methods. 

PET imaging systems are somewhat more complex, and therefore more expensive than are SPECT systems, and the price factor is generally between two and three. The primary cost premium associated with these systems, however, is the need for a cyclotron and its attendant staff combined with the relative complexity of radiopharmaceutical preparation for short half-life isotopes. As of 1996, there are considerable hurdles blocking widespread regulatory approval and full reimbursement of PET studies. 

A special type of substituent effect which has proved veiy valuable in the study of reaction mechanisms is the replacement of an atom by one of its isotopes. Isotopic substitution most often involves replacing protium by deuterium (or tritium) but is applicable to nuclei other than hydrogen. The quantitative differences are largest, however, for hydrogen, because its isotopes have the largest relative mass differences. Isotopic substitution usually has no effect on the qualitative chemical reactivity of the substrate, but often has an easily measured effect on the rate at which reaction occurs. Let us consider how this modification of the rate arises. Initially, the discussion will concern primary kinetic isotope effects, those in which a bond to the isotopically substituted atom is broken in the rate-determining step. We will use C—H bonds as the specific topic of discussion, but the same concepts apply for other elements. 

Fig. 4.9. DifiBoing zero-point energies ofprotium- and deuterium-substituted molecules as the cause of primary kinetic isotope effects.

Detailed analysis of isotope effects reveals that there are many other factors that can contribute to the overall effect in addition to the dominant change in bond vibrations. For that reason, it is not possible to quantitatively predict the magnitude of either primary or seconday isotope effects for a given reaction. Furthermore, there is not a sharp numerical division between primary and secondary effects, especially in the range between 1 and 2. 

The details of proton-transfer processes can also be probed by examination of solvent isotope effects, for example, by comparing the rates of a reaction in H2O versus D2O. The solvent isotope effect can be either normal or inverse, depending on the nature of the proton-transfer process in the reaction mechanism. D3O+ is a stronger acid than H3O+. As a result, reactants in D2O solution are somewhat more extensively protonated than in H2O at identical acid concentration. A reaction that involves a rapid equilibrium protonation will proceed faster in D2O than in H2O because of the higher concentration of the protonated reactant. On the other hand, if proton transfer is part of the rate-determining step, the reaction will be faster in H2O than in D2O because of the normal primary kinetic isotope effect of the type considered in Section 4.5. 

For E2 eliminations in 2-phenylethyl systems with several different leaving groups, both the primary isotope effect and Hammett p values for the reactions are known. Deduce from these data the relationship between the location on the E2 transition state spectrum and the nature of the leaving group i.e., deduce which system has the most El-like transition state and which has the most Elcb-like. Explain your reasoning. 

Isotope effects are also useful in providing insight into other aspects of the mechanisms of individual electrophilic aromatic substitution reactions. In particular, because primary isotope effects are expected only when the breakdown of the c-complex to product is rate-determining, the observation of a substantial points to a rate-... 

Bromination has been shown not to exhibit a primary kinetic isotope effect in the case of benzene, bromobenzene, toluene, or methoxybenzene. There are several examples of substrates which do show significant isotope effects, including substituted anisoles, JV,iV-dimethylanilines, and 1,3,5-trialkylbenzenes. The observation of isotope effects in highly substituted systems seems to be the result of steric factors that can operate in two ways. There may be resistance to the bromine taking up a position coplanar with adjacent substituents in the aromatization step. This would favor return of the ff-complex to reactants. In addition, the steric bulk of several substituents may hinder solvent or other base from assisting in the proton removal. Either factor would allow deprotonation to become rate-controlling. 

Indicate mechanisms that would account for the formation of each product. Show how the isotopic substitution could cause a change in product composition. Does your mechanism predict that the isotopic substitution would give rise to a primary or secondary deuterium kinetic isotope effect Calculate the magnitude of the kinetic isotope effect from the data given. 

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