Prebiotic thiol-catalyzed thioamide bond formation

Thioamide bonds are important intermediates in prebiotic chemistry. In cyanosul- fidic 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 het- erocycle 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. We describe here 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 HCN and sulfide, suggesting poten- tial accumulation on early Earth. Lastly, we demonstrate that thioformamide has a Gibbs energy of hydrolysis (∆G◦r) 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.