Gas and Aqueous Phase Computations on the Keto–Enol Tautomerization of Pyruvic and Zymonic Acids: Implications for Prebiotic Enol Phosphates

Keto-enol tautomerism plays a very important role in pyruvate chemistry and metabolic transformations. The enol form of pyruvate is thermodynamically much less stable, and its tautomerization to the keto form is one of the strongly favored energetic single rearrangements, endowing phosphoenolpyruvate as one of the most potent phosphate donors in biology. In this work, we report the keto-enol rearrangement of pyruvate and pyruvate-derived compounds, such as zymomate, using high-quality density functional theory for the gas phase and molecular dynamics methods for the aqueous phase. Our results indicate a preference for the keto tautomer of pyruvic acid and pyruvate both in the gas as well as in the aqueous phase. Zymonic acid prefers to be in the enol form in gas as well as in an aqueous medium. Tautomerization contributes approximately 42% of the energetic driving force in the hydrolysis of phosphenol pyruvate. Keto tautomer of zymonate, however, is lower in energy in the gas phase, while the enol tautomer, due to its strong solvation free energy, is lower in energy in the aqueous phase. The results of our work are also discussed in the context of astrobiology, where we explore how fundamental carbonyl chemistry such as keto-enol tautomerization reactions may have influenced the selection of phosphoenolpyruvate. We propose a scenario for how the emergence of PEP might have taken place through a process of chemical evolution originating from a wider variety of possible enol phosphates operating within a proto-metabolism.