Kinetic Isotope Effects KIEs

Kezdy-Swinboume method, 26-27 Kinetic element effect, 110-111 Kinetic isotope effects (kie), 214-219 inverse, 217... 

Apart from a few studies (ref. 7), the use of deuterium kinetic isotope effects (kie s) appears to have had limited use in mechanistic studies of electrophilic bromination of olefins. Secondary alpha D-kie s have been reported for two cases, trans-stilbene fi and p-substituted a-d-styrenes 2, these giving relatively small inverse kie s of... 

In addition to the magnetic differences between the deuteron and proton, however, their mass difference may also cause observable effects. A well known example is found in the theory of chemical reactions, where the so called kinetic isotope effects (KIE s) are an important source of information about reaction mechanisms. Also in the field of ESR, such effects may arise, although these have been much less studied than the KIE s. 

Today a good understanding of transition state structure can be obtained through a combination of experimental measurements of kinetic isotope effects (KIE) and computational chemistry methods (Schramm, 1998). The basis for the KIE approach is that incorporation of a heavy isotope, at a specific atom in a substrate molecule, will affect the enzymatic reaction rate to an extent that is correlated with the change in bond vibrational environment for that atom, in going from the ground state to the... 

Hydrogen motion, H+, H or H, is often involved in the rate-limiting step of many enzyme catalysed reactions. Here, QM tunnelling can be important and is reflected in the values of the measured kinetic isotope effects (KIEs) [75], Enzyme motion... 

Corey et al. investigated the kinetic isotopic effect (KIE) in asymmetric dihydroxylation. 12C/13C KIE was measured for the dihydroxylation of styrene, p-nitrostyrene, and 4-methoxy-benzoate (Figure 7).197 The observed similar 12C/13C isotopic effect of two olefinic carbons... 

The photolyses of diazirines 9a and 9b were similarly studied in Ar matrices at 10-34.5 K 59 Eq. 10. Benzylchlorocarbene (10a) and its ct,a-d2 analogue (10b) were observed by UV or IR (10b) spectroscopy, and their decay to styrenes 11 and 12 could be monitored. Tunneling in these 1,2-H(D) shifts was indicated by (a) much higher rates of carbene decay at 10 K than could be anticipated from extrapolation of the 298 K LFP kinetic data, (b) a kinetic isotope effect (KIE) for the 1,2-H(D) shifts estimated at 2000, and (c) little temperature dependence of the rate at low temperature.59 Accepting that QMT is important in the very low temperature H shifts of carbenes 10 and 18, the obvious question becomes is QMT important at higher or even ambient temperatures ... 

Experiments have implied that quantum mechanical effects can be involved in the proton and hydride transfer of several biological processes. Specifically, large kinetic isotope effects (KIE) observed for... 

The present findings suggest that mechanistic and reaction product variations are not necessarily accompanied by a clear difference in reactivity and the TS structure, and hence experimentally observable quantities, such as relative reactivities (Hammett equation) and kinetic isotope effects (KIEs), which are commonly considered to be useful means to detect a change in reaction mechanism (77,72), may not always be useful. 

Since the kinetic constant is independent of the reagent concentration and of the extent of proton loss from the intermediate, the last step is surely not rate limiting and the formation of the intermediate is for this olefin completely rate determining. (20) Consistent with this hypothesis is the lack of a large primary kinetic isotope effect (KIE), kH/kD = 0.97 (0.01), expected for a slow L+ loss when the vinyl bromide is the main product. Taking into account that the rate determining step is the formation of a bromocarbenium-tribromide (bromide) ion pair and that the transition state should be closely related to the intermediate,... 

Table 3 collects the results obtained by different authors on the reaction of 0s04(NH3) with ethylene. Though the methods were not identical, the results are very similar, and in all cases there is a clear preference of the [3+2] over the [2+2] pathway. Additional confirmation was provided by a combined experimental and theoretical study using kinetic isotope effects (KIEs) to compare experiment and theory. Kinetic isotope effects were measured by a new NMR technique [25] and compared to values, which are available from calculated transition states. It showed that indeed only the [3+2] pathway is feasible [10]. 

Secondary a-deuterium kinetic isotope effects (KIEs) have been widely used to determine the mechanism of SN reactions and to elucidate the structure of their transition states (Shiner, 1970a Westaway, 1987a). Some of the significant studies illustrating these principles are presented in this section. 

Isotope effects on rates (so-called kinetic isotope effects, KIE s) of specific reactions will be discussed in detail in a later chapter. The most frequently employed formalism used to discuss KIE s is based on the activated complex (transition state) theory of chemical kinetics and is analogous to the theory of isotope effects on thermodynamic equilibria discussed in this chapter. It is thus appropriate to discuss this theory here. 

Conceptually, the simplest way to measure a kinetic isotope effect (KIE) is to use a non-competitive method, in which two separate kinetic runs are carried out, each starting with a different isotopomer of the reactant. The rate constants for both species are determined and the kinetic isotope effect (KIE) is the ratio of the two rate constants. This procedure is frequently referred to as the direct method . 

The kinetic isotope effect (KIE) has been measured in the reactions of... 

Westaway and co-workers work on kinetic isotope effects (KIEs) has continued.-... 

The kinetic isotope effect (KIE) produced in the photorearrangement of 4-me-thoxyphenyl acetate to 2-hydroxy-5-methoxyacetophenone has been measured by determining the isotope ratios before and after irradiation (k, and ka, respectively) in the starting material and the rearranged products. A value of KIE = kjk, different from unity would indicate that the rearrangement proceeds along an activation energy barrier. This is neither the case for the [48,49] nor for the case of isotope, both included in the carbonyl moiety [49]. In fact, the obtained values are KIE ( C) = 0.9988 0.0051 and KIE ( 0) = 1.0000 0.0023. 

Nearly all kinetic isotope effects (KIE) have their origin in the difference of isotopic mass due to the explicit occurrence of nuclear mass in the Schrodinger equation. In the nonrelativistic Bom-Oppenheimer approximation, isotopic substitution affects only the nuclear part of the Hamiltonian and causes shifts in the rotational, vibrational, and translational eigenvalues and eigenfunctions. In general, reasonable predictions of the effects of these shifts on various kinetic processes can be made from fairly elementary considerations using simple dynamical models. 

Attempts to use intermolecular and intramolecular kinetic isotope effects (KIE s) to identify a complexation step during ortholithiation have so far been inconclusive. Both intramolecular and intermolecular KIE s for the deprotonation of 2 and 3 by s-BuLi... 

Timelines can also be portrayed in charts or figures, as illustrated in excerpt 14D. In fact, charts and figures represent excellent ways to illustrate how smaller, individual projects contribute to larger research goals and how smaller projects complement one another and overlap in time. (Note In excerpt 14D, Kohen uses the following abbreviations in his chart, each defined previously in the proposal hydrogen (H), tritium (T), deuterium (D), kinetic isotope effect (KIE), dihydrofolate reductase (a relatively small protein) (DHFR), and wild type (WT).)... 

The rate of reaction of Mel with [Rh(CO)2l2] was measured and compared with the rate of reaction of Mel and the kinetic isotope effect (KIE) was shown, through ab initio molecular orbital calculations, to be consistent with an 5 2 mechanism proceeding through a linear (Rh-C-I ) transition state [33]. 

The ability to compute the free energy difference between two minima on a PES allows the effect of isotopic substitution on the equilibrium constant between them to be calculated. Similarly, a kinetic isotope effect (KIE) can be predicted from the effect of isotopic substitution on the free energy difference between a minimum and a TS (i.e., a free energy of activation). 

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