Tritium-deuterium kinetic isotope effects, relative

Stern, M. J., Weston, R. E. J. (1974) Phenomenological manifestations of quantum-mechanical tunneling. III. Effect on relative tritium-deuterium kinetic isotope effects, J. Chem. Phys. 60, 2815-2821. 

Figure 8. Relative tritium-deuterium kinetic isotope effect r and individual contributors to r for a model hydrogen-atom abstraction (a),(a ), Vh = Vo = Vt = 10 kcal/mole (b)Xb ), V = 10, V =- 11, Vt - 11.45 heal/mole (28)...

The Northrop-Cleland nomenclature system for isotope effects greatly simplifies their discussion the non-abundant isotope and, in the case of secondary effects, site of substitution are written as superscripts to V or VjK in parentheses, so that °(F/A) refers to an a-deuterium kinetic isotope effect on kcatZ-Klm and (K) refers to an effect on kcat- The effects on individual rate and equilibrium constants are written as superscripts is the p-tritium effect on an equilibrium constant and " k+2 is the effect on the k+2 step. Although in principle potentially ambiguous (e.g. could in principle refer to or the relatively short-lived F), in practice any ambiguity is resolved from the context. 

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. 

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).)... 

If substitution of deuterium for protium in a chemical reaction produces a detectable kinetic isotope effect, substitution of tritium wiU produce an even larger kinetic isotope effect (kii/IcT)) because of the larger mass of tritium and the resultant lower zero-point vibrational energy of a C-T relative to C-D and C-H bond. In a number of chemical and enzymatic reactions, a simple logarithmic proportionahty is observed, known as a SwainSchaad relationship (Swain eta/., 1958) ... 

Fig. 7-13. Relative effect of isotopic mass on reaction kinetics, expressed as ]/m2/mt (where m2 and m, are the masses of the nuclides plotted and the most common stable nuclide of the same element, respectively). Biological fractionation is only likely to be important for elements with atomic masses less than — 20, especially in the case of deuterium and tritium.

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