Replaceability of isotopes

Paneth and his collaborator von Hevesy took the view that isotopes might be chemically identical and began to explore this notion experimentally (Paneth von Hevesy, 1914). They proposed the concept of replaceability of isotopes—that is, they claimed that the replacement of any isotope with another one of the same species would not produce any noticeable chemical effect. They set out to verify the correctness of this view through the law of mass action. For any reaction,... 

Much attention has been devoted in recent years to studies of isotope shifts in NMR spectra caused by the replacement of isotopes with in the molecule. As for the ethynylsilanes, the isotope shifts in the Si NMR spectra have so far been... 

In some cases replacements of isotopes result in spectral and/or fluores cence changes. An interesting application of deuterium/hydrogen exchange is the study of the mobility of different domains of proteins (Englander Kallenbach, 1983). This approach to the study of protein dynamics has already been referred to in section 5.3. The exchange of isotopes into specific positions (for instance deuterium and/or carbon-13) is also widely used to increase the potentialities of NMR investigations. 

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. 

Two techniques, electrochemical reduction (section IIl-C) and Clem-mensen reduction (section ITI-D), have previously been recommended for the direct reduction of isolated ketones to hydrocarbons. Since the applicability of these methods is limited to compounds which can withstand strongly acidic reaction conditions or to cases where isotope scrambling is not a problem, it is desirable to provide milder alternative procedures. Two of the methods discussed in this section, desulfurization of mercaptal derivatives with deuterated Raney nickel (section IV-A) and metal deuteride reduction of tosylhydrazone derivatives (section IV-B), permit the replacement of a carbonyl oxygen by deuterium under neutral or alkaline conditions. 

Replacement of halides with deuterium gas in the presence of a surface catalyst is a less useful reaction, due mainly to the poor isotopic purity of the products. This reaction has been used, however, for the insertion of a deuterium atom at C-7 in various esters of 3j -hydroxy-A -steroids, since it gives less side products resulting from double bond migration. Thus, treatment of the 7a- or 7j5-bromo derivatives (206) with deuterium gas in the presence of 5% palladium-on-calcium carbonate, or Raney nickel catalyst, followed by alkaline hydrolysis, gives the corresponding 3j3-hydroxy-7( -di derivatives (207), the isotope content of which varies from 0.64 to 1.18 atoms of deuterium per mole. The isotope composition and the stereochemistry of the deuterium have not been rigorously established. 

A. I. Shatenshtein, Isotopic Exchange and the Replacement of Hydrogen in Organic Compounds, Consultants Bureau, New York, 1962, p. 105. 

The first term is analogous to the rate expression for the Mn(II[) oxidation of cyclohexanol vide supra) and displays a primary isotope effect of similar magnitude (2.2 at 50 °C). The second term shows an isotope effect of 4.3 for replacement of HCO2H by DCO2H. The oxidations of malonic acid and Hg(l) ° involve [Mn(III)] /[Mn(ll)] terms and these are readily explained by the equilibrium... 

It has been shown in Section 2.1.4 that methanol adsorbate formed from dilute solutions on a porous Pt surface, consists of COad and COHad in a ratio CO COH of ca. 20-30% [14]. The results of isotopic exchange with bulk CO seem to indicate that only the fraction present as COad can be desorbed and replaced by bulk CO. Probably the same arguments as in the case of pure COad can apply. COHad seems to be more strongly bound to the Pt surface and cannot be desorbed. 

This mechanism would predict that a plot of l/d>r vs. 1/[BH2] should be linear with an intercept equal to l/Oisc. The experimental results 1 have been plotted in this way in Figure 3.1. The straight lines in Figure 3.1 are consistent with but do not prove the suggested mechanism. The slope for the lower line (BH2) is equal to 0.05, while that for the upper is 0.133. This difference in rate upon replacement of a hydrogen atom with deuterium indicates that the reaction is subject to an isotope effect. Therefore the abstraction... 

Because fluorine is relatively sensitive to its environment and has such a large range of chemical shifts, considerable changes in chemical shift can be observed when a nearby atom is replaced by an isotope. For example, replacement of 12C by 13C for the atom to which the fluorine is attached, gives rise to a quite measurable shift, usually to lower frequency. A consequence of this isotope effect is the observation that the 13C satellites in a fluorine spectrum are not symmetrical about the 12C—F resonance. 

The use of selective isotope replacement of carbon and hydrogen atoms in the structure of xanthophylls in combination with LHCII reconstitution should greatly aid the assignment of multiple v4 twisting bands. This assignment would help localize the areas of distortion within the carotenoid molecule and understand the possible causes of this distortion. 

The time-resolved, chemical behavior of FL depends on the solvent. Irradiation of DAF in cyclohexane gives FLH The lifetime of FL in cyclohexane is 1.4 ns, and the ratio of products obtained (26) indicates that both direct insertion and abstraction-recombination mechanisms are operating (Griller et al., 1984b). Replacement of the cyclohexane by its deuteriated counterpart reveals a kinetic isotope effect of ca 2 (Table 5). 

Even nowadays the application of radioactive isotopes is the most sensitive method for the analysis of biomolecules or their reaction products. Besides the low detection limits, the replacement of a naturally overbalancing stable isotope by its radioactive analogue does not interfere with the physical or chemical properties of the enzyme (with some exceptions for hydrogens). Figure 6 lists some frequently used radioactive isotopes and their half-life periods. 

The replacement of light isotope with heavy isotope in activated state also lowers the energy. Let the lowering in energy in activation state be represented as AZ o H has been observed that AE is less than AE0 and, therefore, ratio of k/kj > 1. When the bond involving the isotope element in activated complex is completely broken AE and k/k will be maximum. However, when the bonds in activated complex is stronger than in the initial molecule, i.e. AE > A/i o, the value of ktk will be less than unity. This is called reverse isotope effect. 

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