Common and Potentially Prebiotic Origin for Precursors of Nucleotide Synthesis and Activation
Open accessAbstract
We have recently shown that 2-aminoimidazole is a superior nucleotide activating group for nonenzymatic RNA copying. Here we describe a prebiotic synthesis of 2-aminoimidazole that shares a common mechanistic pathway with that of 2-aminooxazole, a previously described key intermediate in prebiotic nucleotide synthesis. In the presence of glycolaldehyde, cyanamide, phosphate and ammonium ion, both 2-aminoimidazole and 2-aminooxazole are produced, with higher concentrations of ammonium ion and acidic pH favoring the former. Given a 1:1 mixture of 2-aminoimidazole and 2-aminooxazole, glyceraldehyde preferentially reacts and cyclizes with the latter, forming a mixture of pentose aminooxazolines, and leaving free 2-aminoimidazole available for nucleotide activation. The common synthetic origin of 2-aminoimidazole and 2-aminooxazole and their distinct reactivities are suggestive of a reaction network that could lead to both the synthesis of RNA monomers and to their subsequent chemical activation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
2AI can be generated in the same reaction mixture as the related heterocycle 2-aminooxazole, a precursor of the pyrimidine nucleotides.
“it can be generated in the same reaction mixture as the related heterocycle 2-aminooxazole, a precursor of the pyrimidine nucleotides”
From Protocells and RNA Self-Replication (2018) · cites this paper as Fahrenbach et al. 2017
The radiolytic reaction network also produced 2-aminoimidazole, a product favoured by increasing concentrations of NH4Cl when reacting glycolaldehyde with cyanamide.
“This radiolytic reaction network also produced 2-aminoimidazole, a product which is favoured by increasing concentrations of NH4Cl when reacting glycolaldehyde with cyanamide [131].”
From Prebiotic Reaction Networks in Water (2020) · cites this paper as [131]
The dry-down step increases the concentration of solutes, promoting synthesis of 2-aminooxazole and 2-aminoimidazole.
“The dry-down step also serves to increase the concentration of the solutes, which promotes the synthesis of 2-aminooxazole 27 as well as 2-aminoimidazole [131].”
From Prebiotic Reaction Networks in Water (2020) · cites this paper as [131]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions.
Powner, M. W., Gerland, B., & Sutherland, J. D. (2009) · Nature · doi:10.1038/nature08013 · Cited by 1,383 · see citing works
Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism
Patel, B. H., Percivalle, C., Ritson, D. J., Duffy, C. D., & Sutherland, J. D. (2015) · Nature Chemistry · doi:10.1038/nchem.2202 · Cited by 949 · see citing works
Comprehensive Review in Current Developments of Imidazole-Based Medicinal Chemistry
Zhang, L., Peng, X.-M., Damu, G. L. V., Geng, R., & Zhou, C. (2013) · Medicinal Research Reviews · doi:10.1002/med.21290 · Cited by 802 · see citing works
Catalytic triads and their relatives
Dodson, G. (1998) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01254-7 · Cited by 660 · see citing works
Progress Toward Synthetic Cells
Blain, J. C., & Szostak, J. W. (2014) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-080411-124036 · Cited by 314 · see citing works
Self-citationEnhanced Nonenzymatic RNA Copying with 2-Aminoimidazole Activated Nucleotides
Li, L., Prywes, N., Tam, C. P., O’Flaherty, D. K., Lelyveld, V. S., Izgu, E. C., Pal, A., & Szostak, J. W. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.6b13148 · Cited by 176 · see citing works
Self-citationPrebiotic activation processes
LOHRMANN, R., & ORGEL, L. E. (1973) · Nature · doi:10.1038/244418a0 · Cited by 154 · see citing works
Islam, S., Bučar, D.-K., & Powner, M. W. (2017) · Nature Chemistry · doi:10.1038/nchem.2703 · Cited by 115 · see citing works
A Highly Reactive Imidazolium-Bridged Dinucleotide Intermediate in Nonenzymatic RNA Primer Extension
Walton, T., & Szostak, J. W. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b07977 · Cited by 102 · see citing works
Self-citationDirect Assembly of Nucleoside Precursors from Two‐ and Three‐Carbon Units
Anastasi, C., Crowe, M. A., Powner, M. W., & Sutherland, J. D. (2006) · Angewandte Chemie International Edition · doi:10.1002/anie.200601267 · Cited by 86 · see citing works
Wu, T., & Orgel, L. E. (1992) · Journal of the American Chemical Society · doi:10.1021/ja00040a002 · Cited by 79 · see citing works
Efficient and environmentally friendly synthesis of 2-amino-imidazole
Weinmann, H., Harre, M., Koenig, K., et al. (2002) · Tetrahedron Letters · doi:10.1016/s0040-4039(01)02226-2 · Cited by 76 · see citing works
Weber, A. L. (1981) · Journal of Molecular Evolution · doi:10.1007/bf01733208 · Cited by 61 · see citing works
63. The reaction of cyanamide with α-amino-acetals and α-amino-aldehydes
Lawson, A. (1956) · Journal of the Chemical Society (Resumed) · doi:10.1039/jr9560000307 · Cited by 60 · see citing works
Ferris, J. P., Huang, C., & Hagan, W. J. (1989) · Nucleosides and Nucleotides · doi:10.1080/07328318908054184 · Cited by 50 · see citing works
A new synthesis of alkyl and aryl 2‐aminoimidazoles
Lancini, G., & Lazzari, E. (1966) · Journal of Heterocyclic Chemistry · doi:10.1002/jhet.5570030208 · Cited by 44 · see citing works
The prebiotic synthesis and catalytic role of imidazoles and other condensing agents
Oró, J., Basile, B., Cortes, S., Shen, C., & Yamrom, T. (2004) · Origins of Life · doi:10.1007/bf00933663 · Cited by 42 · see citing works
Potentially prebiotic syntheses of condensed phosphates
Keefe, A. D., & Miller, S. L. (1996) · Origins of Life and Evolution of Biospheres · doi:10.1007/bf01808157 · Cited by 33 · see citing works
Uncovering the Thermodynamics of Monomer Binding for RNA Replication
Izgü, E. Ç., Fahrenbach, A. C., Zhang, N., Li, L., Zhang, W., Larsen, A. T., Blain, J. C., & Szostak, J. W. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b02707 · Cited by 30 · see citing works
Self-citationReaction of Imidazoles with Cyanogen Bromide: Cyanation at N 1 or Bromination at C 2?
McCallum, P. B. W., GRIMMETT, M. R., Blackman, A. G., et al. (1999) · Australian Journal of Chemistry · doi:10.1071/c98105 · Cited by 27 · see citing works
Polymerization of unprotected 2'-deoxyribonucleoside 5'-phosphates at elevated temperature
Pongs, O., & Ts’o, P. O. P. (1971) · Journal of the American Chemical Society · doi:10.1021/ja00749a046 · Cited by 23 · see citing works
The prebiotic synthesis of oligonucleotides
Or�, J., & Stephen-Sherwood, E. (1974) · Origins of Life and Evolution of Biospheres · doi:10.1007/bf00927021 · Cited by 22 · see citing works
Li, L., Lelyveld, V. S., Prywes, N., et al. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b00784 · Cited by 20 · see citing works
Self-citationVázquez-Salazar, A., Tan, G. K., Stockton, A. M., Fani, R., Becerra, A., & Lazcano, A. (2016) · Origins of Life and Evolution of Biospheres · doi:10.1007/s11084-016-9525-y · Cited by 16 · see citing works
Template-directed Chemical Ligation to Obtain 3′-3′ and 5′-5′ Phosphodiester DNA Linkages
Chen, H., Du, F., Chen, G., Streckenbach, F., Yasmeen, A., Zhao, Y. F., & Tang, Z. (2014) · Scientific Reports · doi:10.1038/srep04595 · Cited by 12 · see citing works
Template-directed nonenzymatic oligonucleotide synthesis: lessons from synthetic chemistry
Fahrenbach, A. C. (2015) · Pure and Applied Chemistry · doi:10.1515/pac-2014-1004 · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Protocells and RNA Self-Replication
Joyce, G. F., & Szostak, J. W. (2018) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a034801 · Cited by 308 · see citing works
Self-citationCamprubí, E., de Leeuw, J. W., House, C. H., Raulin, F., Russell, M. J., Spang, A., Tirumalai, M. R., & Westall, F. (2019) · Space Science Reviews · doi:10.1007/s11214-019-0624-8 · Cited by 84 · see citing works
“phate and ammonium react under low pH conditions (Fahrenbach et al. 2017).”
BackgroundThe protometabolic nature of prebiotic chemistry
Nogal, N., Sanz-Sánchez, M., Vela-Gallego, S., Ruiz-Mirazo, K., & de la Escosura, A. (2023) · Chemical Society Reviews · doi:10.1039/d3cs00594a · Cited by 61 · see citing works
A Continuous Reaction Network that Produces RNA Precursors
Yi, R., Tran, Q. P., Ali, S., Yoda, I., Adam, Z. R., Cleaves, H. J., & Fahrenbach, A. C. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1922139117 · Cited by 45 · see citing works
Self-citationPrebiotic Reaction Networks in Water
Tran, Q. P., Adam, Z. R., & Fahrenbach, A. C. (2020) · Life · doi:10.3390/life10120352 · Cited by 32 · see citing works
Self-citationRadiolysis Generates a Complex Organosynthetic Chemical Network
Adam, Z., Fahrenbach, A. C., Jacobson, S. M., Kacar, B., & Zubarev, D. Y. (2019) · doi:10.26434/chemrxiv.10148684 · Cited by 34 · see citing works
Self-citationLiu, Z., Wu, L.-F., Bond, A. D., & Sutherland, J. D. (2020) · Chemical Communications · doi:10.1039/d0cc05752e · Cited by 18 · see citing works
Radiolytic Synthesis of Cyanogen Chloride, Cyanamide and Simple Sugar Precursors
Yi, R., Hongo, Y., Yoda, I., Adam, Z. R., & Fahrenbach, A. C. (2018) · ChemistrySelect · doi:10.1002/slct.201802242 · Cited by 18 · see citing works
Self-citationAmino acids catalyse RNA formation under ambient alkaline conditions
Rout, S. K., Wunnava, S., Krepl, M., Cassone, G., Šponer, J. E., Mast, C. B., Powner, M. W., & Braun, D. (2025) · Nature Communications · doi:10.1038/s41467-025-60359-3 · Cited by 15 · see citing works
Prolinyl Nucleotides Drive Enzyme‐Free Genetic Copying of RNA
Welsch, F., Kervio, E., Tremmel, P., & Richert, C. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202307591 · Cited by 13 · see citing works
Radicals in Prebiotic Chemistry
Lim, R. W. J., & Fahrenbach, A. C. (2020) · Pure and Applied Chemistry · doi:10.1515/pac-2020-0805 · Cited by 8 · see citing works
Self-citation
- Authors
- Fahrenbach, A. C., Giurgiu, C., Tam, C. P., Li, L., Hongo, Y., Aono, M., & Szostak, J. W.
- Affiliations
- Tokyo Institute of Technology (JP)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Szostak, Jack W.
- ORCID
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-06-22
- Volume
- 139
- Issue
- 26
- Pages
- 8780-8783
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- PMC
- PMC6326526
- OpenAlex
- W2630155643
- Cited by
- 96
- References
- 26
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 8 · 2023: 10 · 2022: 6 · 2021: 10 · 2020: 18 · 2019: 12 · 2018: 15 · 2017: 4
- FWCI
- 7.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of the American Chemical Society (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Division of Chemistry (CHE-1607034)
- Simons Foundation (290363)
- Life Sciences Research Foundation (NA)
- Japan Society for the Promotion of Science (JP26106003)
- Topics
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Reaction Mechanisms
- Keywords
- 2-aminoimidazole, 2-aminooxazole, prebiotic synthesis, nucleotide activation, nucleotide precursors, glycolaldehyde, glyceraldehyde, cyanamide, ammonium, origin of life
- MeSH terms
- Aminoimidazole Carboxamide, Nucleotides, Oxazoles, Molecular Structure, Prebiotics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
