Oxygen isotope effects as probes of electron transfer mechanisms and structures of activated O2.

Competitively determined oxygen ((18)O) isotope effects can be powerful probes of chemical and biological transformations involving molecular oxygen as well as superoxide and hydrogen peroxide. They play a complementary role to crystallography and spectroscopy in the study of activated oxygen intermediates by forging a link between electronic/vibrational structure and the bonding that occurs within ground and transition states along the reaction coordinate. Such analyses can be used to assess the plausibility of intermediates and their catalytic relevance in oxidative processes. This Account describes efforts to advance oxygen kinetic isotope effects ((18)O KIEs) and equilibrium isotope effects ((18)O EIEs) as mechanistic probes of reactive, oxygen-derived species. We focus primarily on transition metal mediated oxidations, outlining both advances over the past five years and current limitations of this approach. Computational methods are now being developed to probe transition states and the accompanying kinetic isotope effects. In particular, we describe the importance of using a full-frequency model to accurately predict the magnitudes as well as the temperature dependence of the isotope effects. Earlier studies have used a "cut-off model," which employs only a few isotopic vibrational modes, and such models tend to overestimate (18)O EIEs. Researchers in mechanistic biological inorganic chemistry would like to differentiate "inner-sphere" from "outer-sphere" reactivity of O(2), a designation that describes the extent of the bonding interaction between metal and oxygen in the transition state. Though this problem remains unsolved, we expect that this isotopic approach will help differentiate these processes. For example, comparisons of (18)O KIEs to (18)O EIEs provide benchmarks that allow us to calibrate computationally derived reaction coordinates. Once the physical origins of heavy atom isotope effects are better understood, researchers will be able to apply the competitive isotope fractionation technique to a wide range of pressing problems in small molecule chemistry and biochemistry.