From Zero to Hero: The Cyanide-Free Formation of Amino Acids and Amides from Acetylene, Ammonia and Carbon Monoxide in Aqueous Environments in a Simulated Hadean Scenario

Abstract

Amino acids are one of the most important building blocks of life. During the biochemical process of translation, cells sequentially connect amino acids via amide bonds to synthesize proteins, using the genetic information in messenger RNA (mRNA) as a template. From a prebiotic perspective (i.e., without enzymatic catalysis), joining amino acids to peptides via amide bonds is difficult due to the highly endergonic nature of the condensation reaction. We show here that amides can be formed in reactions catalyzed by the transition metal sulfides from acetylene, carbon monoxide and ammonia under aqueous conditions. Some α- and β-amino acids were also formed under the same conditions, demonstrating an alternative cyanide-free path for the formation of amino acids in prebiotic environments. Experiments performed with stable isotope labeled precursors, like ¹⁵NH₄Cl and ¹³C-acetylene, enabled the accurate mass spectroscopic identification of the products formed from the starting materials and their composition. Reactions catalyzed using the transition metal sulfides seem to offer a promising alternative pathway for the formation of amides and amino acids in prebiotic environments, bypassing the challenges posed by the highly endergonic condensation reaction. These findings shed light on the potential mechanisms by which the building blocks of life could have originated on early Earth.

Keywords: acetylene; amide; amino acids; hydrothermal conditions; origin of life; peptide bond; transition metal sulfides.

Scheme 1

Basic process of the Strecker reaction. The reaction proceeds via the nucleophilic addition of ammonia to the aldehyde (1). This generally extends to the iminium ion (2). The cyanide adds to this electrophilic species, resulting in an α-aminonitrile (3). The amino acid (4) is ultimately formed through hydrolysis.

Figure 1

Different mass spectra of propionamide. (A) is from run 1 (Table S2), (B) is from a run with ¹³C₂H₂, (C) is from a run with ¹³CO and (D) is from a run with ¹⁵NH₄Cl. The typical mass of m/z = 130 results from the loss of the t-butyl group from TBDMS.

Figure 2

Different mass spectra of succinamic acid. (A) is from run 1 (Table S2), (B) is from a run with ¹³C₂H₂, (C) is from a run with ¹³CO and (D) is from a run with ¹⁵NH₄Cl. The typical mass of m/z = 288 results from the loss of the t-butyl group from the TBDMS.

Figure 3

Different mass spectra of alanine. Measurement was performed in single ion monitoring (SIM) mode. Shown are the masses of typical fragments of TBDMS-derivatized amino acids. In the case of alanine these are m/z = 260, m/z = 232 and m/z = 158. (A) is from run 1 (Table S2), (B) is from a run with ¹³C₂H₂, (C) is from a run with ¹³CO and (D) is from a run with ¹⁵NH₄Cl.

Figure 4

Different mass spectra of aspartic acid. (A) is from run 1 (Table S2), (B) is from a run with ¹³C₂H₂, (C) is from a run with ¹³CO and (D) is from a run with ¹⁵NH₄Cl. Typical mass fragments of TBDMS-derivatized aspartic acid are m/z = 418, m/z = 390 and m/z = 302.

Scheme 2

Retrosynthesis of propionamide from one molecule of ammonia, acetylene and carbon monoxide (A); succinamic acid from one molecule of ammonia, one molecule of acetylene, two molecules of carbon monoxide and one molecule of water (B); alanine from one molecule of ammonia, one and a half molecules of acetylene and two molecules of water (C); and aspartic acid from one molecule of ammonia and acetylene and two molecules of carbon monoxide and water (D).

Figure 5

Formation of propionamide, succinamic acid, alanine and aspartic acid with different metal ions as metal sulfide catalysts. Mixtures of transition metal catalysts contain 50/50 (mol%) or 33/33/33 (mol%) of the corresponding metal-sulfides, respectively.

Figure 6

Formation of propionamide (green), succinamic acid (violet), alanine (blue) and aspartic acid (orange) in the presence of NiS at different pH values. pH values were measured at the end of the reaction time.

Figure 7

Time-dependent NiS catalyzed formation of propionamide (green), succinamic acid (violet), alanine (blue) and aspartic acid (orange) from acetylene, carbon monoxide and ammonia.

Figure 8

Formation of propionamide (green), succinamic acid (violet), alanine (blue) and aspartic acid (orange) with different concentration of Na₂S and therefore different concentration of active catalysts.

Scheme 3

Formation of amides from acetylene as starting material. Shown is the formation of propionamide (A), acetamide (B) and formamide (C). (D) shows the simultaneously occurring reaction of CO into formamide.

Scheme 4

Possible mechanisms of the formation of amino acids in our setup. (A): proposed mechanism of NH₃ addition to α, β unsaturated carboxylic acids. (B,C): mechanism for the example of α, β alanine and aspartic acid. (D): competing reaction with the addition of water and (E): another possible mechanism via reductive amination of α-ketoacids.