The Reaction of Aminonitriles with Aminothiols: A Way to Thiol-Containing Peptides and Nitrogen Heterocycles in the Primitive Earth Ocean

Abstract

The Strecker reaction of aldehydes with ammonia and hydrogen cyanide first leads to α-aminonitriles, which are then hydrolyzed to α-amino acids. However, before reacting with water, these aminonitriles can be trapped by aminothiols, such as cysteine or homocysteine, to give 5- or 6-membered ring heterocycles, which in turn are hydrolyzed to dipeptides. We propose that this two-step process enabled the formation of thiol-containing dipeptides in the primitive ocean. These small peptides are able to promote the formation of other peptide bonds and of heterocyclic molecules. Theoretical calculations support our experimental results. They predict that α-aminonitriles should be more reactive than other nitriles, and that imidazoles should be formed from transiently formed amidinonitriles. Overall, this set of reactions delineates a possible early stage of the development of organic chemistry, hence of life, on Earth dominated by nitriles and thiol-rich peptides (TRP).

Cysteine Chemistry in Connection with Abiogenesis

“…The Pinner reaction of nitriles with thiols under aqueous conditions leads to thioesters . We have shown that using this reaction, aminonitriles can be transformed into aminothioesters under prebiotic conditions . Such chemistry could bridge a prebiotic chemistry dominated by nitriles and the Strecker reaction, and the thioester world imagined by de Duve .…”

“…MALDI mass analysis of this precipitate demonstrated that it was constituted of a complex mixture containing some relatively high mass molecules (up to at least 1500). However, the structure of these products, which in principle could be polythiazolines (from the reactions of nitriles with aminothiols) or polypeptides, (Cys) n (from thiazoline rings hydrolysis), was not clearly identified.…”

“…In order to test this possibility, we synthesized the trifluoroacetate salt of thioester 12 (Scheme ). The MALDI mass spectrum of the precipitate resulting from its evolution in water at pH 6 (Figure and Supplementary Information) demonstrated that this precipitate is a mixture of polycysteines of various lengths regularly separated by the mass of a single Cys residue, 103. The higher measured mass corresponds to a Cys 45 structure (containing 4 disulfide bridges).…”

“…Finally, in order to test the possibility to use the reaction of nitriles with aminothiols to obtain cysteine‐rich polypeptides, we synthesized CysValCN 13 (Scheme ). Its polymer was analysed both by MALDI and by ASAP high‐resolution mass spectrometry.…”

Chemistry of Homocysteine Thiolactone in A Prebiotic Perspective

“…Recently we have reported the synthesis of various dipeptides starting from cysteine and aminonitriles under plausible prebiotic conditions [11]. Such dipeptides, as well as longer peptides containing thiol groups, could have been promoters of other reactions in the “thioester world” proposed by De Duve [12,13], perhaps in a way similar to what is happening today in the non-ribosomal synthesis of peptides [14].…”