The Trapping of the OH Radical by Coenzyme Q. A Theoretical and Experimental Study

Several pathways for the attack of the hydroxyl radical on coenzyme Q, as a prototypical chemical reaction involved in biological antioxidant actions, were theoretically analyzed by hybrid density functional theory computations, at the BHandHLYP/6-31G level. We found that the most favorable pathways are the hydrogen abstraction reaction from the phenolic hydrogen on the reduced form (ubiquinol), and the electrophilic OH addition on the oxidized form (ubiquinone). The reaction paths for the two mechanisms were traced independently. Following the direct dynamics method, the respective thermal rate constants were calculated using variational transition-state theory with multidimensional small-curvature tunneling. The experimental rate constants for the reaction of ubiquinol and ubiquinone with hydroxyl radicals produced via the Fenton's reaction in phosphate-buffered water solution at pH 7 were also measured. We found, first, that the reactivity in gas-phase (theoretical approach) is dominated by the OH addition mechanism on ubiquinone, and second, that a good agreement exists between the ratio of the rate constants determined from theoretical and experimental approaches for the reaction of oxidized and reduced forms of coenzyme Q with hydroxyl radicals. It is a very fast reaction, practically diffusion-controlled, with an inverse dependence of the thermal rate constants on temperature and therefore, a negative activation energy, both theoretically and experimentally. The influence of the tunneling factor was negligible. The analysis of the enthalpy and entropy contributions to the Gibbs free energy profile allowed us to understand the negative value of the activation energy.