Analyzing the efficiency of proton transfer to carbon in Kirby’s enzyme model—a computational approach

Abstract

A mechanistic study using ab initio and DFT calculation methods on the intramolecular ring-closing of enol ethers 1Z, 1E, and 2 (Kirby’s enzyme models for aldolase and isomerase) has revealed that proton transfer is the rate determining step and involves two stages: re-organization of the global minimum structure (having the lowest enthalpic energy and a relatively long distance between the two reactive centers, r) to a more organized ground state conformation (having the smallest r distance among all the conformations), and a second stage by which the proton is transferred from the organized state to the corresponding transition state. The energy needed for the first stage to occur is dependent on the rotation barrier for the proton to be in proximity to the C C double bond carbon (proximity effects), whereas, that needed for the second step is largely affected by the strain energies of the reactant and the corresponding product. In addition, it was found that the oxocarbocation intermediate involved in the proton transfer is unstable and undergoes ring-closing to the corresponding product with zero activation energy. Further, the calculated DFT effective molarities (EM) for 1Z, 1E, and 2 were found to correlate strongly with experimental EM values.