Solvent Dependence of the Kinetic Isotope Effect in the Reaction of Ascorbate with the 2,2,6,6-Tetramethylpiperidine-1-oxyl Radical: Tunnelling in a Small Molecule Reaction

Abstract

The oxidation of ascorbate with the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical in water and water-dioxane mixed solvent has been demonstrated to be a proton-coupled electron transfer (PCET) process, involving hydrogen tunnelling at room temperature. The magnitude of the kinetic isotope effect (KIE) k(H)/k(D) in the reaction increases with decrease of the solvent polarity. The evidence comprise: (a) the spectroscopic and kinetic evidence for the interaction of ascorbate and TEMPO; (b) the observation of KIEs k(H)/k(D) of 24.2(0.6) in water and 31.1(1.1) in 1:1 v/v water-diox. (diox = dioxane), at 298 K; (c) the observation of isotope effect on the Arrhenius prefactor, A(H)/A(D) of 0.6(0.2) in the reaction in water and 1.2(0.2) in 1:1 v/v water-diox solvent; (d) the observation of isotope differences in the enthalpies of activation in water and D(2)O, Delta(r)H(double dagger) (in H(2)O) = 31.0(0.4) kJ/mol, Delta(r)H(double dagger) (in D(2)O) = 40.0 (0.5) kJ/mol; in 1:1 v/v water-diox and 1:1 v/v D(2)O-diox, Delta(r)H(double dagger) (in H(2)O/diox) = 23.9(0.2) kJ/mol, Delta(r)H(double dagger) (in D(2)O/diox) = 32.1(0.3) kJ/mol; (e) the temperature dependence of the KIEs in water and 1:1 v/v water-dioxane; these KIEs range from 27.3 at 285.4 K to 19.1 at 317.4 K in water and from 34.3 to 24.6 at the corresponding temperatures in 1:1 v/v water-diox, respectively; (f) the observation of an increase of the KIE in 10-40% v/v dioxane-water solvents relative to the KIE in water alone. There is a weak solvent dependence of the rate constant on going from water to 1:1 v/v water-diox. solvent, from 2.20(0.03) mol(-1) dm(3) s(-1) to 5.50(0.14) mol(-1) dm(3) s(-1), respectively, which originates from the mutual compensation of the enthalpy and entropy of activation.

Kinetic isotope effect in the oxidation of unsaturated fatty acids

“…In par ticular, the KIE value is 10.6-15 for the reaction sty rene peroxy radicals with substituted phenols [33,34], 24 for the reaction of ascorbate with 2,2,6,6 tetrame thylpiperidine 1 oxyl [35], 18 for the vitamin E radi cal with ubiquinol 10 [36], 3-8 for the reaction of ascorbate with the free radical formed from α toco pherol in micellar solutions [37]. Note that the oxida tion of PUFAs is so far the only example in which the KIE value changes nonadditively with the composi tion of the reaction mixture composed of nondeuter ated and deuterated compounds.…”

Kinetic solvent effects in organic reactions

“…The reaction between ascorbate and TEMPO radical was studied experimentally. [50] The mechanism was best explained by proton-coupled electron transfer (PCET) ( Figure 5), where an electron and proton are transferred simultaneously but between different sets of orbitals. This mechanism differs from SPLET, as the electron and proton are transferred in a single elementary step rather than sequentially.…”

Kinetic Solvent Effects in Organic Reactions

“…Furthermore, Nielsen and Ingold found that the β In some types of hydrogen abstraction reactions, the effect of changing the solvent is low. The reaction between ascorbate and 2,2,6,6-tetramethylpiperidine-1-oxyl radical was studied experimentally 49 . The mechanism was best explained by proton-coupled electron transfer (PCET) (Figure 5), where an electron and proton are transferred simultaneously but between different sets of orbitals.…”