Isotope effects reaction kinetics

Transition state theory has been useful in providing a rationale for the so-called kinetic isotope effect. The kinetic isotope effect is used by enzy-mologists to probe various aspects of mechanism. Importantly, measured kinetic isotope effects have also been used to monitor if non-classical behaviour is a feature of enzyme-catalysed hydrogen transfer reactions. The kinetic isotope effect arises because of the differential reactivity of, for example, a C-H (protium), a C-D (deuterium) and a C-T (tritium) bond. 

Isotope effect, see Kinetic isotope effect Isotopes, and virtual isomerization reactions, 18-19... 

Hvistendahl, G. Uggerad, E. Secondary Isotope Effect on Kinetic Energy Release and Reaction Symmetry. Org. Mass Spectrom. 1985,20,541-542. 

An isotope effect (either kinetic or equihbrium) resulting from reactions in which the different isotopes occupy chemically equivalent alternative reactive sites within the same molecular entity. In such cases, isotopicaUy distinct products are formed. See Intermolecular Isotope Effect Kinetic Isotope Effect Equilibrium Isotope Effect lUPAC (1979) Pure and Appl. Chem. 51, 1725. 

For elements of low atomic numbers, the mass differences between the isotopes of an element are large enough for many physical, chemical, and biological processes or reactions to fractionate or change the relative proportions of various isotopes. Two different types of processes— equilibrium isotope effects and kinetic isotope effects—cause isotope fractionation. As a consequence of fractionation processes, waters and solutes often develop unique isotopic compositions (ratios of heavy to light isotopes) that may be indicative of their source or of the processes that formed them. 

Unlike primary kinetic isotope effects, secondary kinetic isotope effects arise due to presence of stable isotope at sites close to point of reaction and consequently influence the geometry of the reaction intermediates. Although the absolute values are much lower than those observed for primary effects, secondary kinetic isotope effects yield important information pertaining to the progress of the reaction and transition states involved therein [100,124,125],... 

Experience with model calculations for equilibrium isotope effects and kinetic isotope effects, when using conventional TST, shows that the RGM is valid in the common circumstance in which the effects of coupled vibrational motions cancel between reactant and product states, or between reactant and transition states. The natural coupling expected between the various bends and stretches of the bonds in a methyl group is largely the same in the reactant state and transition state in the acetyl transfer example, so the free-energy effects of multiple isotopic substitutions are strictly additive. In the case of the glutamate dehydrogenase reaction of Fig. 

Solvent kinetic isotope effects (SKIEs) in H2O/D2O mixtures on the reaction of /)NPP catalyzed by calcineurin gave a small normal value of 1.35. Proton inventory and fractionation data are consistent with a mechanism involving a single proton transfer from a metal-bound water, although due to the small KSIE value and the inherent experimental error of the proton inventory technique, the participation of a second proton could not he excluded. Further information has been furnished by heavy-atom isotope effects. Reaction of NPP catalyzed by APP shows that phosphoryl transfer is fully rate limiting. However, for calcineurin the... 

All of the isotope effects discussed so far have been primary kinetic isotope effects. A secondary kinetic isotope effect can arise when a bond to the isotope is not broken during the rate-limiting step of a reaction. Generally, secondary kinetic isotope effects are much smaller in magnitude than are primary kinetic isotope effects. Secondary kinetic isotope effects can nevertheless serve as useful probes of transition state structure because the magnitude of the effect generally increases as the transition structure changes from reactant-like to product-like. ° ... 

Kinetic isotope effect studies. Kinetic isotope effect (KIE) measurements are a powerful approach for the elucidation of reaction mechanism and the quantification of rate constants. This gives insight into molecular mechanisms and increases one s understanding of molecular interaction. The KIE is dependent on the mass difference between the isotopes and the largest practical value for a carbon KIE ratio is obtained using (Axelsson et al. 1990 Matsson et al. 

Stradiotto and Tobisch collaborated to investigate the proposed mechanism for lr(l)-catalyzed cyclohydroamination of unactivated aUcenes with primary and secondary amines. A combination of kinetic investigations, including kinetic isotope effects, reaction monitoring, substrate scope investigations, and computational... 

One way in which the step of the reaction in which the proton is lost might be slowed down, and perhaps made kinetically important (with i), would be to carry out nitration at high acidities. Nitration of pentadeuteronitrobenzene in 97-4% sulphuric acid failed to reveal such an effect. In fact, nitrations under a variety of conditions fail to show a kinetic isotope effect. 

The cases of pentamethylbenzene and anthracene reacting with nitronium tetrafluoroborate in sulpholan were mentioned above. Each compound forms a stable intermediate very rapidly, and the intermediate then decomposes slowly. It seems that here we have cases where the first stage of the two-step process is very rapid (reaction may even be occurring upon encounter), but the second stages are slow either because of steric factors or because of the feeble basicity of the solvent. The course of the subsequent slow decomposition of the intermediate from pentamethylbenzene is not yet fully understood, but it gives only a poor yield of pentamethylnitrobenzene. The intermediate from anthracene decomposes at a measurable speed to 9-nitroanthracene and the observations are compatible with a two-step mechanism in which k i k E and i[N02" ] > / i. There is a kinetic isotope effect (table 6.1), its value for the reaction in acetonitrile being near to the... 

By protodetritiation of the thiazolium salt (152) and of 2 tritiothiamine (153) Kemp and O Brien (432) measured a kinetic isotope effect, of 2.7 for (152). They evaluated the rate of protonation of the corresponding yiides and found that the enzyme-mediated reaction of thiamine with pyruvate is at least 10 times faster than the maximum rate possible with 152. The scale of this rate ratio establishes the presence within the enzyme of a higher concentration of thiamine ylide than can be realized in water. Thus a major role of the enzyme might be to change the relative thermodynamic stabilities of thiamine and its ylide (432). 

The azo coupling reaction proceeds by the electrophilic aromatic substitution mechanism. In the case of 4-chlorobenzenediazonium compound with l-naphthol-4-sulfonic acid [84-87-7] the reaction is not base-catalyzed, but that with l-naphthol-3-sulfonic acid and 2-naphthol-8-sulfonic acid [92-40-0] is moderately and strongly base-catalyzed, respectively. The different rates of reaction agree with kinetic studies of hydrogen isotope effects in coupling components. The magnitude of the isotope effect increases with increased steric hindrance at the coupler reaction site. The addition of bases, even if pH is not changed, can affect the reaction rate. In polar aprotic media, reaction rate is different with alkyl-ammonium ions. Cationic, anionic, and nonionic surfactants can also influence the reaction rate (27). 

Most of the chemical properties of tritium are common to those of the other hydrogen isotopes. However, notable deviations in chemical behavior result from isotope effects and from enhanced reaction kinetics induced by the ( -emission in tritium systems. Isotope exchange between tritium and other hydrogen isotopes is an interesting manifestation of the special chemical properties of tritium. 

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. 

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. 

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