The formation of polypeptides on the early Earth has been a long-standing problem in the field of prebiotic chemistry. Although it is generally accepted that amino acids were present on the prebiotic Earth, the plausible mechanism to form long chain polypeptides is still unclear. Because of the high activation energies and the formation of side products, direct peptide bond formation will not occur unless high temperature or activating agents are used. Here, we found a simple system composed of hydroxy acids and amino acids that is capable of forming peptide bonds under mild conditions. Hydroxy acids form metastable oligoesters in the oscillating (hot dry/cool wet) system and transform into mixed copolymers via the ester-amide exchange reaction. To further understand the kinetic behavior of this copolymerization, we first tracked the growth of initial species from a valine/ lactic acid mixture in a closed system reactor. A mathematical model was developed to simulate the reactions and evaluate the rate constants at different temperatures. We found these reactions can be described by the empirical Arrhenius equation even when the reaction occurred in the solid (dry) state. Further calculations for activation parameters showed that the ester-mediated pathway facilitates amide bond formation by lowering activation entropies. Finally, we combined the experimental and model-based approaches to identify an ideal feeding policy for the growth of long chain polymers. These results not only demonstrate a simple system exhibiting key features for the emergence of peptides at mild conditions, but also provide a theoretical framework that illustrates why the ester-mediated pathway for peptide bond formation would have been more favorable on the early Earth, compared to peptide bond formation without the aid of hydroxy acids.

Prebiotic depsipeptide formation from the ester-amide exchange reaction

253rd National Meeting (2017)

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