Kinetic isotope effects diminished

If the isotope sensitive step is reversible the equations get more complicated and cannot be solved explicitly for the intrinsic isotope effects (unless Cf = 0, or the equilibrium isotope effect is unity). The last two equations in Equation 11.48 demonstrate that a normal deuterium kinetic isotope effect diminishes the apparent commitment if both isotopes are present. Thus 13(V/K) is smaller than 13(V/K)d when both isotope effects are related to the same step. 

Interestingly, in a comparison of the CD3 and CHj carbenes, an unusual temperature dependence of the kinetic isotope effect was observed. In contrast to typical reactions, the ratio of rates of H versus D shift, k /ko, actually increased as temperature was raised. In fact, k was measured to be larger than k at 248 K. It was suggested that these results required a normal temperature dependence of the isotope effect for the classical component of the reaction, but an unusual diminished isotope effect for the QMT reaction. 

The principal goal of most studies of kinetic isotope effects on enzymatic reactions is to deduce intrinsic rate constants, which, in turn, can be correlated with the geometric features, that is the structure, of the corresponding transition states. Formal kinetics provides several options for reaching this goal. For example, as we have seen above, changes in concentration can diminish the commitment to the point where the KIE experimental value corresponds directly to the intrinsic kinetic... 

An S Ar (nucleophilic substitution at aromatic carbon atom) mechanism has been proposed for these reactions. Both nonenzymatic and enzymatic reactions that proceed via this mechanism typically exhibit inverse solvent kinetic isotope effects. This observation is in agreement with the example above since the thiolate form of glutathione plays the role of the nucleophile role in dehalogenation reactions. Thus values of solvent kinetic isotope effects obtained for the C13S mutant, which catalyzes only the initial steps of these reactions, do not agree with this mechanism. Rather, the observed normal solvent isotope effect supports a mechanism in which step(s) that have either no solvent kinetic isotope effect at all, or an inverse effect, and which occur after the elimination step, are kinetically significant and diminish the observed solvent kinetic isotope effect. 

As outlined above, the process of substitution by the nitronium ion is satisfactorily described by an SE2 mechanism in which k2 E > k v In certain circumstances the process could be changed so that this condition did not hold, and the step in which the proton is lost could become kinetically important. One such circumstance is that in which the hydrogen atom being replaced is situated between bulky substituents steric hindrance would then make it difficult for the nitro group to move from its position in the intermediate complex to that between the bulky substituents k2 would be diminished, and a kinetic isotope effect might appear. It is for this reason that 1,3,5-tri-f-butylbenzene and its derivatives are interesting (table 6.1) whilst the hydrocarbon undergoes... 

Stabilization of a carbocation intermediate by benzylic conjugation, as in the 1-phenylethyl system shown in entry 8, leads to substitution with diminished stereosped-ficity. A thorough analysis of stereochemical, kinetic, and isotope effect data on solvolysis reactions of 1-phenylethyl chloride has been carried out. The system has been analyzed in terms of the fate of the intimate ion-pair and solvent-separated ion-pair intermediates. From this analysis, it has been estimated that for every 100 molecules of 1-phenylethyl chloride that undergo ionization to an intimate ion pair (in trifluoroethanol), 80 return to starting material of retained configuration, 7 return to inverted starting material, and 13 go on to the solvent-separated ion pair. 

Comparison between the diminished form of isotope effects can be employed to determine the relative steady-state contribution of different components to the hmiting values of kinetic parameters. For example, comparing diminished... 

Stabilization of cationic intermediates by conjugation with an aromatic ring, as in the 1-phenylethyl system, leads to nucleophilic substitution with diminished stereospecificity. A thorough analysis of stereochemical, kinetic, and isotope effect data on solvolysis reactions of 1-phenylethyl chloride has been carried out. For the ion-pair equilibria... 

---