Isotope effects heavy atom

Next to the isotope effects of hydrogen the most studied element has been carbon where the effects range as high as 15% with C measurements of radioactivity are inherently of lower precision than mass spectrometric measurements making C the preferable isotope. Results from isotope effects on carbon can be most informative as the majority of organic reactions involve carbon bond fission. 

Carbon isotope effects can be used in a straightforward way to determine whether a bond cleaves in the rate-limiting step. For example the isotope effect on the decarboxylation of 2,4-dihydroxybenzoic acid [30a] varies with the nature and concentration of acid catalyst suggesting a change in rate-determining step (Eqn. 49). 

For a simple bond fission it is doubtful if comparison of the observed isotope effect with the theoretical maximum will give a trustworthy estimate of the position of the transition state small effects are therefore ambiguous as diagnostic tools and must be coupled with other experiments. Another example involving decarboxylation is the bromine-catalysed decomposition of 3,5-dibromo-4-hydroxy-benzoic acid (Eqn. 50) [30b]. 

In the absence of added bromide ion the C effect is 1.00 + 0.003 indicating no bond changes in the labelled carbon in the rate-limiting step in the presence of 0.3 M Br the effect rises to 1.045 + 0.001 as might be expected for full rupture consistent with rate-limiting decomposition of the intermediate (Eqn. 50). 

Intermolecular isotope effects /3Sci//37ci ranging from 0.95 0.06 to 1.17 0.08 have been reported for loss of a chlorine atom from protonated chloroaromatic molecules [938], The isotope effects were 

The loss of HC1 from the negative ions formed by attachment of Cl to glucose, acetophenone and benzoic acid exhibited intermolecular isotope effects /h35ci//h37ci of about 1.14, 1.04 and 1.19, respectively [938]. The isotope effects were based on peak heights in Cl mass spectra. 

Intramolecular carbon isotope effects have been determined for the McLafferty rearrangement in metastable a-ethylbutyrophenone ions using molecules specifically labelled with 13C at either one of the [3 or at one of the 7 positions. The isotope effects /c2H4/fi3CCH obtained were 0.095 0.005 for the 7-13C compound and 1.017 0.d07 for the 3-13C compound [849]. 

The natural abundance of 13C has been exploited in an investigation of carbon isotope effects on loss of methane from metastable butane ions [64]. An inverse isotope effect /12cH //j3ch of about 0.9 was reported. The significance of this result is unclear as there appear to be several reaction pathways contributing to the loss of methane [928]. 

Intramolecular chlorine isotope effects have been determined in metastable ion decompositions induced by El of carbon tetrachloride, silicon tetrachloride, hexachloroethane and hexachlorosilane [687]. In all cases, the isotope effects were normal, i.e. losses involving the lighter isotope Cl were favoured. The loss of a chlorine atom from (CCl3) and from (SiCl4) showed isotope effects greater than 1.50. Other 

The error limits on some of the determinations were large (up to 0.35) because peaks were only partially resolved and peak areas were therefore difficult to measure accurately. 

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The observation of a heavy-atom isotope effect, therefore, allows one to determine whether C—X bond weakening (a decrease in force constant) has occurred when the reactant is converted into the transition state of the rate-determining step. Calculations by... 

Saunders10 and by Sims and coworkers11 have shown that the magnitude of the leaving-group heavy-atom isotope effect varies linearly with the extent of C—X bond rupture in the transition state for concerted elimination reactions and for nucleophilic substitution reactions, respectively. Since the magnitude of the isotope effect is directly related to the amount of C—X bond rupture in the transition state, these isotope effects provide detailed information about the structure of the transition state. 

Further Discussion, Heavy Atom Isotope Effects, Secondary Isotope Effects 319... 

For historic and practical reasons hydrogen isotope effects are usually considered separately from heavy-atom isotope effects (i.e. 160/180, 160/170, etc.). The historic reason stems from the fact that prior to the mid-sixties analysis using the complete equation to describe isotope effects via computer calculations was impossible in most laboratories and it was necessary to employ various approximations. For H/D isotope effects the basic equation KIE = MMI x EXC x ZPE (see Equations 4.146 and 4.147) was often drastically simplified (with varying success) to KIE ZPE because of the dominant role of the zero point energy term. However that simplification is not possible when the relative contributions from MMI (mass moment of inertia) and EXC (excitation) become important, as they are for heavy atom isotope effects. This is because the isotope sensitive vibrational frequency differences are smaller for heavy atom than for H/D substitution. Presently... 

For heavy atom isotope effects tunneling is relatively unimportant and the TST model suffices. As an example the dehalogenation of 1,2-dichloroethane (DCE) to 2-chloroethanol catalyzed by haloalkane dehalogenase DhlA is discussed below. This example has been chosen because the chlorine kinetic isotope effect for this reaction has been computed using three different schemes, and this system is among the most thoroughly studied examples of heavy atom isotope effects in enzymatic reactions. 

HEAVY ATOM ISOTOPE EFFECT KINETIC ISOTOPE EFFECTS... 

KINETIC ISOTOPE EFFECT EQUILIBRIUM ISOTOPE EFFECT SOLVENT ISOTOPE EFFECT HEAVY ATOM ISOTOPE EFFECT INTRAMOLECULAR KINETIC ISOTOPE EFFECT... 

Another method of seeking evidence of the EIcBirr mechanism is to exam heavy-atom isotope effects in the leaving group. Of course, these should be much more significant in an E2 process because the bond is breaking in the transition state. For example, Thibblin and co-workersfound that in the base-induced elimination of an alkyl halide in which the p-carbon is unusually acidic (indene derivative, 12), moderately strong bases (triethylamine and methoxide) lead to a significant Cl/ Cl isotope effect = 1.010 1.009, where a maximum effect of... 

A review (91 references) on electrophilic and nucleophilic reactions of trivalent phosphorus acid derivatives, reactions of two-coordinate phosphorus compounds, and miscellaneous reactions has appeared.228 Earlier in this review we looked at the heavy-atom isotope effects on reactions of Co(III)-bound /vnitrophenyl phosphate,186 the uranyl ion hydrolysis of /vnitrophcnyl phosphodiesters (218)-(220),190 and the Th(IV) hydrolysis of these.191... 

Buncel, E. and Saunders, W.H. Jr. (Eds), (1992) Heavy Atom Isotope Effects. Elsevier, Amsterdam. 

Paneth, P. (1992) How to measure heavy atom isotope effects. Chapter 2 in E. Buncel and W.J. Saunders Jr. (Eds) Isotopes in Organic Chemistry (vol 8). Elsevier, Amsterdam. 

The process occurring here is reminiscent of the N.I.H. shift, which is well known to occur in iron hydroxylases such as cytochrome P-450 and mammalian PAH [1,167], For example, action of PAH on [4-3H]phenylalanine produces >90% [3-3H]tyrosine. Here, a presumed electrophilic iron-oxy species produces a carbonium ion intermediate from which a 1,2-shift occurs, giving a resonance stabilized cation rearomatization through loss of H+ (or 3H+) gives the observed product as a result of a heavy atom isotope effect. Thus, it appears that the N.I.H. shift mechanism for copper has been discovered for a chemical model system prior to its observation in proteins. 

Heavy Atom Isotope Effects as Probes of Small Molecule Activation... 

HEAVY ATOM ISOTOPE EFFECTS AS PROBES OF SMALL MOLECULE ACTIVATION... 

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