Thermodynamic parameters of activation for the uncatalyzed decarboxylation of malonate has been computed in aqueous solution and compared to experimental observation. A mechanism is proposed, indicating a tri-membered cyclic arrangement of water molecules participate in the selective stabilization of the ground state structure. The M06-2X functional with the 6-31+G* basis set was used with a discrete-continuum model, where three explicit water molecules are defined along with Tomasi’s polarizable continuum model (PCM). The cyclic water structure was computed, forming a strong hydrogen bond network with the non-decarboxylating moiety of malonate in the ground state. However, in the decarboxylation transition structure, the hydrogen bond network broke and lost stability. The experimental enthalpy of activation, Δ‡H, and Gibbs free energy of transition, Δ‡G, for malonate are 30.0 kcal/mol and 29.4 kcal/mol, respectively: whereas the computed Δ‡H and Δ‡G are 33.4 kcal/mol and 30.9 kcal/mol, respectively. The novel, non-enzymatic model provides an understanding of the non-enzymatic behavior of similar compounds, and potential in describing the decarboxylation mechanisms in decarboxylases.

Ground state stabilization of non-enzymatic β-keto acid decarboxylation in aqueous solution

251st National Meeting (2016)

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