Prebiotic thiol-catalyzed thioamide bond formation

Thioamide bonds are important intermediates in prebiotic chemistry. In cyanosulfidic prebiotic chemistry, they serve as crucial intermediates in the pathways that lead to the formation of many important biomolecules (e.g., amino acids). They can also serve as purine and pyrimidine precursors, the two classes of heterocycle employed in genetic molecules. Despite their importance, the formation of thioamide bonds from nitriles under prebiotic conditions has required large excesses of sulfide or compounds with unknown prebiotic sources. Here, we describe the thiol-catalyzed formation of thioamide bonds from nitriles. We show that the formation of the simplest of these compounds, thioformamide, forms readily in spark-discharge experiments from hydrogen cyanide, sulfide, and a methanethiol catalyst, suggesting potential accumulation on early Earth. Lastly, we demonstrate that thioformamide has a Gibbs energy of hydrolysis ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>Δ</mml:mi> <mml:msubsup><mml:mi>G</mml:mi> <mml:mi>r</mml:mi> <mml:mo>∘</mml:mo></mml:msubsup> </mml:mrow> </mml:math> ) comparable to other energy-currencies on early Earth such as pyrophosphate and thioester bonds. Overall, our findings imply that thioamides might have been abundant on early Earth and served a variety of functions during chemical evolution.