Unusual Kinetic Isotope Effects of Deuterium Reinforced Polyunsaturated Fatty Acids in Tocopherol-Mediated Free Radical Chain Oxidations

Substitution of –CD(2)– at the reactive centers of linoleic and linolenic acids reduces the rate of abstraction of D by a tocopheryl radical by as much as 36-fold, compared to the abstraction of H from a corresponding –CH(2)– center. This H atom transfer reaction is the rate-determining step in the tocopherol-mediated peroxidation of lipids in human low-density lipoproteins, a process that has been linked to coronary artery disease. The unanticipated large kinetic isotope effects reported here for the tocopherol-mediated oxidation of linoleic and linolenic acids and esters suggests that tunneling makes this process favorable

Can a Secondary Isotope Effect Be Larger than a Primary?

Primary and secondary ¹⁸O equilibrium isotope effects on the acidities of a variety of Brønsted and Lewis acids centered on carbon, boron, nitrogen, and phosphorus were computed by density-functional theory. For many of these acids, the secondary isotope effect was found to be larger than the primary isotope effect. This is a counterintuitive result, because the H atom that is lost is closer to the ¹⁸O atom that is responsible for the primary isotope effect. The relative magnitudes of the isotope effects can be associated with the vibrational frequency and zero-point energy of the XO vibrations, which are greater than those of the XO vibrations. However, the difference between these contributions is small, and the major responsibility for the larger secondary isotope effect comes from the moment-of-inertia factor, which depends on the position of the ¹⁸O atom relative to the principal axes of rotation