B prior to the cleavage of the C-H or C-D bond. In such a scenario, an isotope effect may be observed in Experiment C (where choice of the isotope can take place even after substrate binding) but not in Experiment B (since the choice of whether C-H or C-D bond cleaves is already made as soon as the substrate binds irreversibly). In contrast to Experiment B, the reaction does not need to be halted at low consumption of isotopic starting material to obtain an accurate kH/kD, since the ratio of H and D in the starting material is 1:1, regardless of the extent of conversion. One non-C-H activation example of different isotope effects being observed in the case of intermolecular (Experiment B) and intramolecular (Experiment C) competition is the photolysis of diphenyldiazomethane in the presence of t-butylamine. To explain this result, the formation of diphenylcarbene, followed by irreversible nucleophilic attack by t-butylamine was proposed. Because there is little isotopic difference in the rate of nucleophilic attack, the intermolecular experiment resulted in a KIE close to 1. In the intramolecular case, however, the product ratio is determined by the proton transfer that occurs after the nucleophilic attack, a process for which there is a substantial KIE of 2.6. Thus, Experiments A, B, and C will give results of differing levels of precision and require different experimental setup and ways of analyzing data. As a result, the feasibility of each type of experiment will depend on the kinetic and stoichiometric profile of the reaction, as well as the physical characteristics of the reaction mixture (e.g., homogeneous vs. heterogeneous). Moreover, as noted in the paragraph above, the experiments provide kinetic isotope effect data for different steps of a multi-step reaction, depending on the relative locations of the rate-limiting step, product-determining steps, and/or C-H/D cleavage step. The hypothetical examples below illustrate common scenarios. Consider the following reaction coordinate diagram. For a reaction with this profile, all three experiments (A, B, and C) will yield a significant primary kinetic isotope effect: On the other hand, if a reaction follows the following energy profile, in which the C-H or C-D bond cleavage is irreversible but occurs after the rate-determining step (RDS), no significant kinetic isotope effect will be observed with Experiment A, since the overall rate is not affected by the isotopic substitution. Nevertheless, the irreversible C-H bond cleavage step will give a primary kinetic isotope