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Prebiotic Chemistry I Tom Maimone Baran Lab Prebiotic Chemistry I Tom Maimone "Deducing the mechanism of the origin of life on earth has always remained a fascinating but unsolved puzzle. Some have even considered it too difficult for scientific study, because the direct evidence is long gone, and we can only work by plausible inference." R.H. Crabtree (Where Smokers Rule, Science, 1997, 276, 222) "It's a long way from slime to Mozart." D.G. Blackmond quoting G.M. Whitesides (Scripps Lecture, 2008) "....Among the scientists engaged in active research on the problem of biogenesis, native synthetic organic chemists are a small minority; scientists actively moving behond a merely passive interest in this basic problem are mostly biologists, biochemists, physical chemists, physicists, earth and planetary scientists. The situation is in a way reminiscent of the DNA structure problem, which had been attacked and solved by non-chemists and, in retrospect, revealed itself as one that would have been a major, if not the major problem that nature had in store for natural products chemistry." "Biogenesis, as a problem of science, is lastly going to be a problem of synthesis. The origin of life cannot be 'discovered', it has to be re-invented." -A. Eschenmoser, Tetrahedron, 2007, 63, 12821-12844. 1. Primitive Chemical Synthesis: What is possible in a laboratory setting? 2. Chirality: How and where did it come from? 1 Baran Lab Prebiotic Chemistry I Tom Maimone Origins of organic compounds: This would appear simple in theory: A. They came here or B. They were made here Murchison Meteorite At 11 am (local time) on september 28th, 1969 a large type carbonaceous chondrite type meterorite fell in the small town of Murchison in Victoria, Australia. Its organic composition has spawned a flurry of interest that continues even into the 21st century "Meteor, we call this here being in burger heaven." - J. Dirt "Evidence for Extraterrestrial Amino-Acids and Hydrocarbons in the Murchison Meteorite" -Knenvolden et. al. Nature. 1970, 228, 923. -Anaylsis of the meteorite indicated glycine, alanine, glutamic acid, valine, and proline, 2-methylalanine, sarcosine, and a "complex mixture of alkanes." -Both enantiomers (in nearly equal amounts) were detected for each amino acid " The unique distribution of amino-acids in the Murchison meteorite cannot be explained satisfactorally on the basis of contamination by human hands." "Distribution and Enantiomeric composition of amino acids in the Murchsion Meteorite" -M.H Engel, B. Nagy. Nature. 1982, 296, 837. enantioenrichment of several proteogenic amino acids are reported, while some others (non-proteo) are reported racemic "On the reported optical activity of amino acids in the Murchison Meterorite" -Bada et. al. Nature. 1983, 301, 494. This paper calls into question Engels data regarding ee's of the amino acids and points to contamination. "Isotopic Evidence for Extraterrestrial non-racemic amino acids in the Murchison Meteorite" -Engel nd Macko. Nature. 1997, 389, 265. 15N abundance shows murchison enantiomers amino acids are not from earth, thus L-amino acids are preferred not only on earth 2 Baran Lab Prebiotic Chemistry I Tom Maimone Atmospheric Conundrum There is no general agreement on the composition of the primitive earth, with the exception that it was most likely not highly oxidizing (No O2) Strongly Reducing: Neutral: "Reduction of Carbon Dioxide in Aqueous CH4 + N2 + H2O CO2 + N2 + H2O Solutions by Ionizing Radiation" or W.M. Garrison, D.C. Morrison, J.G. Hamilton, A.A. Benson, M. Calvin. CH4 + NH3 + H2O or Science, 1951, 114, 416-418. CO2 + H2 + N2 favored by favored by prebiotic chemists atmospheric chemists General Experiments: Helium ions 14CO + H O 14 2 2 CO2H (40-meV) Helium 14 ions CO2 + H2O + FeSO4 14CH O + 14CO H (40-meV) 2 2 Conclusion: -CO2 can be reduced to CO2H using solely radiation and H2O -The Process can be somewhat efficient in the presence of inorganic additives(In the FeSO4 experiments, ~25% of the dissolved CO2 was reduced to a mixture of CO2H and CH2O 2 Baran Lab Prebiotic Chemistry I Tom Maimone The Urey-Miller Experiment (1953) S. L. Miller, Science, 1953, 117, 528 "Although Oparin's "prebiotic soup" theory had gained popularity with biologists, it had gone unnoticed in other fields of science." O O O H O O 2 OH OH OH CH4 + NH3 + H2 electric NH2 NH2 OH NH2 discharge O O H2N H2N OH OH 2 Baran Lab Prebiotic Chemistry I Tom Maimone Prebiotic Amino Acid Chemistry - HCN readily forms a oligomeric structures by base catalysis - As early as 1876, it was shown that mild alkaline hydrolysis of these oligomers yields glycine (R. Wipperman, Ber., 1876, 767. T. Volker, Angew. Chem. 1960, 72, 379) basic O pH hydrolysis HCN "oligomers" H2N OH - This chemistry was extended to show the formation of even more aa's by Oro "Amino-acid Synthesis from Hydrogen Cyanide under Possible Primitive Earth Conditions" J. Oro, S.S. Kamat. Nature, 1961, 190, 442-443. O O O 3M NH OH 4 O unidentified HCN OH H2N OH 70°C OH compounds 25 days NH2 OH NH2 Like the Oro study this paper concerns the study of Cyanide as a possible precursor to amino acids, however they report additional compounds in the mixture "Synthesis of Complex Organic Compounds From Simple Precursors: Formation of Amino-Acids, Amino-Acid Polymers, Fatty Acids and Purines From Ammonium Cyanide." -C.U. Lowe, M.W. Rees, R. Markham. Nature, 1963, 199, 219. O O O O O O O H2N O O OH H N OH OH OH 2 H N OH H2N NH2 H2N OH 2 OH OH NH2 NH2 NH2 NH2 NH3 (aq) HCN 90°C 18 h O O O O OH O H2N OH unidentified OH HO OH OH amino acids NH2 NH2 NH2 2 Baran Lab Prebiotic Chemistry I Tom Maimone Pre-biotic Base Pair chemistry: NH2 O NH2 O O N N "Synthesis of Purines Under Possible Primitive Earth Conditions. I. Adenine From N NH N HN HN Hydrogen Cyanide." - J. Oro, A.P. Kimball. Arch. Biochem. Biophys. 1961, 94, 217. N N N N NH O N O N H H 2 O N H H H -This is the seminal paper in the field of base pair prebiotic synthesis Adenine Guanine cytosine Thymine uracil NH2 Purines Pyrimidines N NH3 (aq.) N 1L of 11.1 M HCN could HCN 70°C yield 685 mg. adenine N N H Adenine "Synthesis of Purines Under Possible Primitive Earth Conditions. II. Purine Intermediates From Hydrogen Cyanide ." - J. Oro, A.P. Kimball. Arch. Biochem. Biophys. 1961, 96, 293. The disclosure of byproducts formed in the previous communication NH O O N O O NH2 N NH "and a large number of NH2 O O O other unidentified ultra- OH OH N H NH2 H NH H2N H2N violet absorbing and NH2 N NH 2 H 2 NH2 OH OH NH2 H NH2 fluorescent compounds" 4-aminoimidazole- 4-aminoimidazole- formamide formamadine glycinamide glycine alanine aspartic acid 5-carboxamidine 5-carboxamide "An Unusual Photochemical Rearrangement in the Synthesis of Adenine from Hydrogen Cyanide." J.P Ferris, L.E. Orgel. J. Am. Chem. Soc. 1966, 55, 1074 2 Baran Lab Prebiotic Chemistry I Tom Maimone Prebiotic Base Pair Chemistry - The identity of the HCN oligomers are now known and their chemistry has been extensively studied. - Of particular Interest is the photochemistry of the tetramer: CN NC NH2 h! N H2O major 80% H N N NC NH2 2 H -Eschenmoser has studied the chemistry of the highly reactive dimer 2. NH NH2 CN N H NH2 N N H N N 2 H N N H 2 Baran Lab Prebiotic Chemistry Tom Maimone Prebiotic Amino Acid Chemistry - Prebiotic experiments relating to the pyrimidine synthesis have been in general less successful, but some exceptions are noted "An Efficient Prebiotic Synthesis of Cytosine and Uracil" -M.P. Robertson, S.L. Miller, Nature, 1995, 375, 772-774. NH2 O O 100°C HO N HN CN H N NH 2 2 30 h O N O N H H 53% 2 Baran Lab Prebiotic Chemistry I Tom Maimone Prebiotic Carbohydrate Chemistry - In 1861 Bulerow noted that sugar-like substances are formed when formaldehyde is treated with mild base HO O OH HO O OH - The Formose reactions appears to be the most likely pre-biotic route to early carbohydrates (eg. ribose, deoxyribose) -The mechanism was studied by Breslow in the 1950's HO OH -As you can imagine, prebiotic carbohydrate synthesis are extremely low yielding, "messy" reactions HO ribose deoxyribose Formose Reaction: - Reaction proceeds only under the action of metal ions or basic pH's - redistilled formaldehy does not yield sugars - Addition of glycoaldehyde initiates an autocatalytic cycle based glycoaldehyde on sequential aldol reactions thereby generating more glyco- aldehyde. OH O O O OH 2 2 CHO H H OH OH HO OH ribose Oro and Cox have shown that deoxyribose could also originate via a similar pathway OH HO O OH HO O O glyceraldehyde HO 2 Baran Lab Prebiotic Chemistry I Tom Maimone Prebiotic Peptide Bond Formation "Peptide Formation in the Prebiotic Era: Thermal Condensation of Glycine in Fluctuating Clay Environments." N. Lahav, D. White, S. Chang. Science. 1978, 201, 67-69. It has been proposed that a fluctuating environment of water content and temperature combined with a catalytically active surface, and the opportunity for redistribution of the organic may be ideal for condensation reactions in the prebiotic era As geological relevant models of prebiotic environments, mixtures of clay, H2O, and amino acids were subject to cyclic variations in temperature and H2O content. Consider the complex equilibrium that could exists with only a single amino acid: Wetting-drying and Temp.
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