Cited by 1,711Physical Organic Chemistry and Reaction KineticsOrganophosphorus compounds synthesisOrigins and Evolution of Life

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Why Nature Chose Phosphates

Westheimer, F. H.·1987·Science

DOI 10.1126/science.2434996

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Abstract

Phosphate esters and anhydrides dominate the living world but are seldom used as intermediates by organic chemists. Phosphoric acid is specially adapted for its role in nucleic acids because it can link two nucleotides and still ionize; the resulting negative charge serves both to stabilize the diesters against hydrolysis and to retain the molecules within a lipid membrane. A similar explanation for stability and retention also holds for phosphates that are intermediary metabolites and for phosphates that serve as energy sources. Phosphates with multiple negative charges can react by way of the monomeric metaphosphate ion PO 3 - as an intermediate. No other residue appears to fulfill the multiple roles of phosphate in biochemistry. Stable, negatively charged phosphates react under catalysis by enzymes; organic chemists, who can only rarely use enzymatic catalysis for their reactions, need more highly reactive intermediates than phosphates.

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Etiology of Potentially Primordial Biomolecular Structures: From Vitamin B12to the Nucleic Acids and an Inquiry into the Chemistry of Life’s Origin: A Retrospective
Eschenmoser, A. (2011) · Angewandte Chemie International Edition · doi:10.1002/anie.201103672 · Cited by 193
Main-chain poly(phosphoester)s: History, syntheses, degradation, bio-and flame-retardant applications
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The energy landscape of adenylate kinase during catalysis
Kerns, S. J., Agafonov, R. V., Cho, Y.-J., Pontiggia, F., Otten, R., Pachov, D. V., Kutter, S., Phung, L. A., Murphy, P. N., Thai, V., et al. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2941 · Cited by 192
Phosphorus in prebiotic chemistry
Schwartz, A. W. (2006) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2006.1901 · Cited by 207
Arsenate Replacing Phosphate: Alternative Life Chemistries and Ion Promiscuity
Tawfik, D. S., & Viola, R. E. (2011) · Biochemistry · doi:10.1021/bi200002a · Cited by 184
Adenosine-Phosphate-Fueled, Temporally Programmed Supramolecular Polymers with Multiple Transient States
Dhiman, S., Jain, A., Kumar, M., & George, S. J. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b07469 · Cited by 184
Fancy meeting you here! A fresh look at "prokaryotic" protein phosphorylation
Kennelly, P. J., & Potts, M. (1996) · Journal of Bacteriology · doi:10.1128/jb.178.16.4759-4764.1996 · Cited by 183
Progress in artificial metallonucleases
Mancin, F., Scrimin, P., & Tecilla, P. (2012) · Chemical Communications · doi:10.1039/c2cc30952a · Cited by 181
Prodrugs of Phosphonates and Phosphates: Crossing the Membrane Barrier
Wiemer, A. J., & Wiemer, D. F. (2014) · Topics in current chemistry · doi:10.1007/128_2014_561 · Cited by 183
Why did Nature select phosphate for its dominant roles in biology?
Bowler, M. W., Cliff, M. J., Waltho, J. P., & Blackburn, G. M. (2010) · New Journal of Chemistry · doi:10.1039/b9nj00718k · Cited by 178
Vesicular-Arbuscular Mycorrhizae as Modifiers of Soil Fertility
Barea, J. M. (1991) · Advances in soil science · doi:10.1007/978-1-4612-3030-4_1 · Cited by 178
Biogeochemistry
Schlesinger, W. H. (2013) · Oxford Bibliographies in Ecology · doi:10.1093/obo/9780199830060-0111 · Cited by 175
Stimulus-cleavable chemistry in the field of controlled drug delivery
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Bioenergetics and Life’s Origins
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“These were described by Westheimer (1987) in an excellent review that should be required reading for students interested in the origins of life.”
Background
Are polyphosphates or phosphate esters prebiotic reagents?
Keefe, A., & Miller, S. L. (2004) · Journal of Molecular Evolution · doi:10.1007/bf00173147 · Cited by 126

Authors: Westheimer, F. H.
Affiliations: Harvard University (US)
Corresponding author: Westheimer, F. H.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1987-03-06
Volume: 235
Issue: 4793
Pages: 1173-1178
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.2434996
OpenAlex: W2064761203
Semantic Scholar: 5ca074c6259fad7d448fb8587c394e507dd3ee19
Cited by: 1,711
References: 60
Citations by year: 2026: 68 · 2025: 75 · 2024: 96 · 2023: 89 · 2022: 90 · 2021: 80 · 2020: 77 · 2019: 71 · 2018: 68 · 2017: 71 · 2016: 54 · 2015: 84 · 2014: 69 · 2013: 62 · 2012: 65
FWCI: 14.06
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Physical Sciences › Chemistry › Organic Chemistry › Physical Organic Chemistry and Reaction Kinetics
Physical Sciences › Chemistry › Organic Chemistry › Organophosphorus compounds synthesis
Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
Keywords: phosphate, phosphoric acid, nucleic acids, energy storage, enzyme catalysis
MeSH terms: Amides, Animals, Arsenates, Chemistry, Citrates, Electrochemistry, Humans, Hydrolysis, Ions, Nucleic Acids, Phosphates, RNA, Silicic Acid, Citric Acid, Chemical Phenomena

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