effect with the other two experiments, since the second step would still affect the product distribution. Therefore, with Experiments B and C, it is possible to observe the kinetic isotope effect even if C-H or C-D bond cleavage occurs not in the rate-determining step, but in the product-determining step. Evaluation of rate constant ratios from intermolecular competition reactions In competition reactions, the kinetic isotope effect is calculated from isotopic product or remaining reactant ratios after the reaction, but these ratios depend strongly on the extent of completion of the reaction. Most commonly, the isotopic substrate will consist of molecules labeled in a specific position and their unlabeled, ordinary counterparts. It is also possible in case of 13C kinetic isotope effects, as well as similar cases, to simply rely on the natural abundance of the isotopic carbon for the kinetic isotope effect experiments, eliminating the need for isotopic labeling. The two isotopic substrates will react through the same mechanism, but at different rates. The ratio between the amounts of the two species in the reactants and the products will thus change gradually over the course of the reaction, and this gradual change can be treated in the following manner: Assume that two isotopic molecules, A1 and A2, undergo irreversible competition reactions in the following manner: The kinetic isotope effect for this scenario is found to be: Where F1 and F2 refer to the fraction of conversions for the isotopic species A1 and A2, respectively. Isotopic enrichment of the starting material can be calculated from the dependence of R/R0 on F1 for various kinetic isotope effects, yielding the following figure. Because of the exponential dependence, even very low kinetic isotope effects lead to large changes in isotopic composition of the starting material at high conversions. When the products are followed, the kinetic isotope effect can be calculated using the products ratio RP along with R0 as follows: Kinetic isotope effect measurement at natural abundance Kinetic isotope effect measurement at natural abundance is a simple general method for measuring kinetic isotope effects (KIE) for chemical reactions performed with materials of natural abundance. This technique for measuring KIEs overcomes many limitations of previous KIE measurement methods. KIE measurements from isotopically labeled materials require a new synthesis for each isotopically labeled material (a process often prohibitively difficult), a competition reaction, and an analysis. The KIE measurement at natural abundance avoids these issues by taking advantage