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.2019 Jun 26;9(1):9281.
doi: 10.1038/s41598-019-45310-z.

Nitrogen heterocycles form peptide nucleic acid precursors in complex prebiotic mixtures

Affiliations

Nitrogen heterocycles form peptide nucleic acid precursors in complex prebiotic mixtures

Laura E Rodriguez et al. Sci Rep..

Abstract

The ability to store information is believed to have been crucial for the origin and evolution of life; however, little is known about the genetic polymers relevant to abiogenesis. Nitrogen heterocycles (N-heterocycles) are plausible components of such polymers as they may have been readily available on early Earth and are the means by which the extant genetic macromolecules RNA and DNA store information. Here, we report the reactivity of numerous N-heterocycles in highly complex mixtures, which were generated using a Miller-Urey spark discharge apparatus with either a reducing or neutral atmosphere, to investigate how N-heterocycles are modified under plausible prebiotic conditions. High throughput mass spectrometry was used to identify N-heterocycle adducts. Additionally, tandem mass spectrometry and nuclear magnetic resonance spectroscopy were used to elucidate reaction pathways for select reactions. Remarkably, we found that the majority of N-heterocycles, including the canonical nucleobases, gain short carbonyl side chains in our complex mixtures via a Strecker-like synthesis or Michael addition. These types of N-heterocycle adducts are subunits of the proposed RNA precursor, peptide nucleic acids (PNAs). The ease with which these carbonylated heterocycles form under both reducing and neutral atmospheres is suggestive that PNAs could be prebiotically feasible on early Earth.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Elucidating the structure and formation of the major adduct formed in uracil-spark mixtures. Note that relative mass error given in ppm is calculated as 106 × (massexperimental −masstheoretical)/(masstheoretical). (a) depicts the adduct (m/z 185.0552) identified from DART-MS analysis of uracil incubated with a Miller-Urey spark discharge mixture generated under a reducing atmosphere (0.4 N2, 0.1 CO2, 0.25 CH4, 0.25 H2). (b,c) show the product ion spectra (MS/MS) of the precursor ion (m/z 185.05) at 40% collision energy (14 eV) isolated from uracil incubated with: (b) spark mixture and (c) acrylic acid. (d) shows the MS/MS of uracil-N1-propanoic acid standard. The * indicates an instrument artifact. (e–h)15N-NMR results confirm that acrylic acid adds preferentially to the N1 position of uracil. (e)15N2-Uracil produces two doublets corresponding to N1 (δ132.00) and N3 (δ159.47). (f) Uracil-N1-propanoic acid standard shows that addition at the N1 position shifts the N1 peak downfield (δ135.16) and N3 peak upfield (δ158.71). (g) The four peaks produced from15N2-Uracil incubated with acrylic acid (100 °C x 3 h in D6-dimethyl sulfoxide (D6-DMSO)) correspond to uracil and uracil-N1-propanoic acid. (h) INEPT spectrum of the reaction mixture shows peaks only for nitrogens that have protons directly attached; the N1 peak (δ135.18) was not observed, confirming an addition at the N1 position. Note that the presence of two additional peaks (δ158.26 and δ131.22), suggests that the C5 adduct is a minor product in this reaction. The tops of the spectra have been truncated due to the peak height of uracil. All NMR spectra were obtained in D6-DMSO.
Figure 2
Figure 2
The reactivity of N-heterocycles when incubated with a Miller-Urey spark discharge mixture formed under a reducing (i.e. Red. Spk.) or neutral (i.e. Net. Spk.) atmosphere. Heterocycles are annotated by both their reactivity (background colors) and by which of the most common carbonyls they form (listed as I-V in the legend). Products of hydrolysis (e.g. CN/CONH2/COOH) were counted as a single adduct.*Structures I-V are assignments based on accurate mass measurements (typically <5 ppm error). Note [22,25,31, and51] were not ionized by the DART source and may be more reactive than shown. For compound names and a complete list of corresponding adducts, see Supplementary Tables S3 and S4.
Figure 3
Figure 3
The formation of major adducts identified from N-heterocycles (labeled Het) incubated with Miller-Urey spark discharge mixtures. Major reactions were identified by grouping adducts based on chain length, terminal functional group, and whether the chain was saturated (see Supplementary Table S6 for details). This grouping revealed that the majority contained alkyl and acrylic side chains 1–3 carbons in length with terminal aldehyde or CN/CONH2/COOH groups. Of these groups, only the individual adducts that that were formed by at least 10 N-heterocycles were deemed major and included in this figure. Blue, red, and purple arrows indicate the reaction was robust when N-heterocycles were incubated with mixtures formed under a reducing atmosphere, neutral atmosphere, and both atmospheres, respectively. For clarity, reactants are shown as their nitrile precursors and adducts as their final hydrolysis product (carboxylic acids and aldehydes). *Indicates that it is equally plausible that a structural isomer of the reactant (methacrylonitrile and 3-butyn-2-one for crotonitrile and methylpropiolaldehyde, respectively) attacked the N-heterocycle, forming a structural isomer of the structure shown (see Supplementary Table S2 for the possible structures).
Figure 4
Figure 4
Proposed formation mechanism of cyanamide adducts from N-heterocycles with exocyclic amine groups that were incubated with a neutral spark reaction mixture. (a) Nitrous acid forms nitrosonium ions. (b) The amine groups of N-heterocycles undergo nitrosation and eventually form (c) diazonium cations that undergo (d) nucleophilic substitution with cyanamide (H2N-CN) or the cyanamide derivative, urea (H2N-CONH2).
Figure 5
Figure 5
The chemical evolution of N-heterocycles into plausible pre-RNA monomers in aqueous solutions on early Earth. (a) N-heterocycles may have been delivered to the early Earth by meteorites,. Alternatively, electric discharges through either a reducing or neutral atmosphere produce (b) a complex mixture of organics that can combine to form (c) N-heterocycles,,,. Strongly acidic N-heterocycles (as indicated by low pKaH), such as those with cyano and amide groups conjugated to the ring, deactivate the N-heterocycle for electrophilic attack. Similarly, bulky side chains such as carboxylates also decrease the nucleophilicity of the ring nitrogen, and thus the heterocycle’s reactivity in complex mixtures. (d) Organics formed in electric discharges readily react with a wide range of N-heterocycles to form adducts with a carbonyl side chain, which can serve as precursors for PNA monomers.
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