Evidence for tunneling in base-catalyzed isomerization of glyceraldehyde to dihydroxyacetone by hydride shift under formose conditions

Abstract

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...

Uncertainty quantification for quantum chemical models of complex reaction networks

“…37 Rappoport et al explored the chemical reaction network of the formose reaction automatically based on heuristic guidance and reproduced major reaction pathways as well as experimentally observed products. 20 Recently, hydride shis and associated quantum tunneling were found to play a major role in the formose reaction, [38][39][40] which were not considered in the computational studies. The product ratios are very sensitive to the reaction conditions (e.g., solvent, temperature, and pH) and the amount and type of reactants.…”

Reaction pathway and H/D kinetic isotope effects of the triple proton transfer in a 7‐hydroxyquinoline‐methanol complex in the ground state: A computational approach

“…[44] In the present study, the canonical variational transition state theory (CVT) combined with the small-curvature tunneling (SCT) approximation [37][38][39] was used because this method has been applied to various small-sized to medium-sized reaction systems. [20,24,26,45] Brief explanation of the CVT and SCT is given in Appendix. The rate constants for the GSPT in 7HQ·(MeOH) 2 and isotopomers were calculated in the temperature range of 268-318 K. The mass-scaled reaction coordinate ranged from −3.0 to 3.0 A with the unit of mass being the unified atomic mass unit.…”

“…For example, a k H /k D value of 15 is observed for the hydride shift in the formose reaction at 273 K, [24] and k H /k D values of 26-40 are observed for hydrogen transfer reactions in dicopper complexes at 233 K. [25] Tunneling is proposed to make a significant contribution to these reactions based on the results of quantum chemical calculations. [24,26] In the case of the GSPT of 7HQ·(MeOH) 2 , although the KIE for the triple deuteration is reported to be 5.8 in heptane solution at room temperature, [15] the significance of the tunneling effect on the GSPT in 7HQ·(ROH) 2 is unknown. In the present study, the GSPT of isolated 7HQ·(MeOH) 2 in vacuum was studied by a computational approach to clarify the reaction mechanism of the intrinsic PT process and to obtain deeper insight into the PT reactions in solution.…”

“…Large H/D KIEs have been reported for various proton (or H‐atom or hydride) transfer reactions at ambient temperatures. For example, a k H / k D value of 15 is observed for the hydride shift in the formose reaction at 273 K, and k H / k D values of 26‐40 are observed for hydrogen transfer reactions in dicopper complexes at 233 K . Tunneling is proposed to make a significant contribution to these reactions based on the results of quantum chemical calculations .…”

Physical Organic Chemistry, the Richest Chemical Science

“…Physical organic chemistry plays an important role. For an early example, we discovered the mechanism by which the coenzyme thiamine pyrophosphate catalyzes many important biochemical processes 8. To get a full understanding of the special mechanism involved, we had to synthesize many relevant new compounds and then do kinetic measurements on their reactions.…”