Hydrogen atom transfer reactions between the aldose and ketose are key mechanistic features in formose chemistry by which formaldehyde is converted to higher sugars under credible prebiotic conditions. For one of these transformations, we have investigated whether hydrogen tunneling makes a significant contribution to the mechanism by examining the deuterium kinetic isotope effect associated with the hydrogen transfer during the isomerization of glyceraldehyde to the corresponding dihydroxyacetone. To do this, we developed a quantitative HPLC assay that allowed us to measure the apparent large intrinsic kinetic isotope effect. From the Arrhenius plot of the kinetic isotope effect, the ratio of the preexponential factors A H /A D was 0.28 and the difference in activation energies E a(D) − E a(H) was 9.1 kJ·mol −1 . All these results imply a significant quantum-mechanical tunneling component in the isomerization mechanism. This is supported by multidimensional tunneling calculations using POLYRATE with small curvature tunneling.formose reaction | quantum tunneling | hydride shift | prebiotic reactions W e have described a new mechanism for the formose reaction ( Fig. 1) (1), essentially the same as we had proposed earlier (2) except that the isomerizations of aldose to ketose and the reversal involve a hydride shift rather than an enolization (3-7). Our evidence came from the finding that 2-deuteroglyceraldehyde was converted to 1-deuterodihydroxyacetone under conditions of the formose reaction, with catalysis by Ca 2+ at pH 12. In 2001 Nagorski and Richard had reported an extensive study of the interconversion of glyceraldehyde and dihydroxyacetone by either enolization or hydride shift and had seen that with Zn 2+ the hydride shift mechanism was the exclusive process, by a mechanism closely related to our more recent one (8). We also showed that the isomerization of the ketose erythrulose to the aldose aldotetrose in D 2 O did not lead to deuterium incorporation, as it would have in an enolization process, so it also uses the hydride shift mechanism (1). The first study of the formose reaction in D 2 O was performed by Benner, who saw that no deuterium was incorporated in the intermediates; for some reason he did not invoke hydride shift mechanisms (6).It should be mentioned that we saw that the presence of formaldehyde in the formose reaction in D 2 O led to trapping of any enols formed; without formaldehyde, as in our previous study, there is subsequent deuterium incorporation in dihydroxyacetone, but not significant in glyceraldehyde. We saw that the glyceraldehyde was present almost entirely as its hydrate, a gem diol, but dihydroxyacetone was present mainly as the ketone. This reverses the normally accepted enolization relative rates.
Materials and MethodsIn a hydride shift the distance traveled by the proton is small, comparable to the range of its wave character, so we have investigated the possibility that there is a quantum-mechanical tunneling process involved (9). We find that there is indeed tunnelin...