A Novel Approach to Prebiotic Protein Synthesis

Malcolm E. Schrader

Department of Inorganic and Analytical Chemistry

The Hebrew University of Jerusalem

ILASOL 25th Annual Meeting 25 Dec 2011

Outline

• In today’s talk I explore additional consequences of my approach claiming that prebiotic small atmospheric molecules concentrated and reacted on land rather than in the oceans.

• I first point out some problems with the popular notion that polypeptides, or proteins, were formed prebiotically from condensation of amino acids.

• I then propose, as an alternative, a polymerization based on an extension of our previously proposed mechanism for prebiotic synthesis of RNA.

Conventional Approach

• Condensation of aminoacids, RCH(NH2)COOH,

to form polypeptide. • For example, glycene condensation (R=H)

• HCHNH2COOH + HNHHCHCOOH → HCHNH2CONHCH2COOH +H2O

where CONH contains the amide bond. Where did amino acid come from?

Miller’s Experiments

Miller duplicated, in the laboratory, a reducing atmosphere, essentially as advocated by Urey, consisting of

H2, CH4, NH3, and H20.

With tungsten electrodes in an all glass system, water was boiled in a 500 ml. flask, and its vapor mixed with these reducing gases in a 5 l. flask, where sparking took place.

Choice of Electrical Sparks

• Miller chose electrical sparks for his excitation source in his pioneering experiments. The reason for this choice was apparently mainly for experimental convenience. The assumption was that if it worked with sparks it would probably work with other energy inputs as well.

SPARK EXPERIMENTS [Miller and Urey , 1959] Compound Yield

[moles

( x 105)]

Compound Yield

[moles

( x 105)]

Glycine 63 succinic acid 4

glycolic acid 56 aspartic acid 0.4

sarcosine 5 glutamic acid 0.6

alanine 34 iminodiacetic acid 5.5

lactic acid 31 iminoacetic-propionic acid

1.5

N-methylalanine 1 formic acid 233

α-amino-n-butyric acid 5 acetic acid 15

α-aminoisobutyric acid 0.1 propionic acid 13

α-hydroxybutyric acid 5 urea 2

β-alanine 15 N-methyl urea 1.5

Leakage of Air

• Modern vacuum techniques have emphasized the futility of preventing seemingly small, but sometimes highly significant, leakages of air into ordinary reaction apparatus.

• Nowadays, an all glass and metal system is required for many purposes. (10-10 torr or better).

• An organic reaction system of course cannot come anywhere near to the tightness of even an old 10-5 torr system.

Does the Leak Matter?• However of, course, reaction of the high concentration organics will usually swamp any effects of ordinary O2 in the small amount of air leaked.

• At this point we digress to discuss a type of O2 that is not ordinary, namely singlet O2 .

Dioxygen

• Most molecules exist in a stable singlet ground state, with possibilities of unstable electronically excited states.

• The latter are singlets, on occasion”long-lived” triplets

• In di-oxygen this is reversed.

• The ground state is a stable triplet, and the excited states are singlets.

Molecular orbitals of ground state (triplet) dioxygen

Molecular Orbital of Singlet DiOxygenMolecular

AtomicAtomic

2Pz 2Py 2Px2Px 2Py 2Pz

*

* *

2S2S

1S1S

*

*

E

1O2 and 3O2 with Linoleic Acid

0.4

0.8

1.2

1.6

Abs

orba

nce

at 2

33 n

m

3O 2

1 O2

200 400 600 800 1,000

Reaction Time in Minutes

0

Dioxygen from Electrical Discharge

“ A large amount of evidence is now available to support the presence of

appreciable quantities of electronically excited molecules in oxygen which has been subjected to electrical discharge”.

• R. E. Marsh, Sharon G. Furnival and H. I. Schiff (1965). Photochemistry and Photobiology (1965) 4, 971-977. “The Production of Electronically Excited Oxygen Molecules and their Reactions with Ozone”.

•

Conclusions thus far and Question

• There is no reliable experimental evidence supporting the hypothesis that amino acids were formed from reaction in an assumed prebiotic reducing atmosphere.

• Furthermore, presently accepted early earth models postulate a nearly neutral atmosphere rather than a reducing one.

• So, could there really have been a prebiotic polypeptide (protein backbone), and if so, how did it come about?

RNA OLIGOMER UNIT

Ferris, 2004

Old speculation

5HCN →Adenine

Old speculation

• 5HCHO → Pentose

• But why not 6HCHO → hexose ?

since hexoses are stable while the pentoses

are metastable.

RNA OLIGOMER UNIT

Ferris, 2004

Cyanomethanol Hypothesis

HCN mixes with similarly deposited formaldehyde from raindrops

HCN + HCHO → CH2(CN)OH (13)

5CH2(CN)OH → adenosine + H2O (14)

This provides explanation for pentose (rather than hexose) inclusion in RNA/DNA

Schrader, M. E. (2009) J. Geophys. Res. 114, D15305

Does cyanomethanol react to give other prebiotic polymers in addition to RNA?

Polypeptide (Protein Backbone) from Cyanomethanol

• H H H• NΞC─C─OH NΞC─C─OH NΞC─C─OH • H H H• ↓ ↓↓↓• H H H• NΞC─C─N ─ C ─C ─ N ─ C ─ C ─ OH• H H ║ H H ║ H• O O

Bond Energies of Amino-acid Condensation (kcal/mole)

Breaking Energy Forming EnergyO 90 O 92.8

║ ║

C ─ OH C ─ NH

H ─ N ─ C 98.8 H ─ OH 117.5

H

188.8 TOTALS 210.3

Bond Energies of Cyanomethanol Polymerization (kcal/mole)

• Breaking Energy Forming Energy • H2C ─ OH 90 O ═ C 176

• NΞC ─ CH2 212.6 O ═ C ─ NH 72.8

• CH2O ─ H 101.5 N ─ H 98.8

• H2C ─ NH 72.8

• amide resonance 20.0

• 404.1 TOTALS 429.4

Conclusions 1

• There is no reliable experimental evidence that amino acids are a product of excitation of a model primordial reducing atmosphere.

• A plausible speculation, however,based on the presently accepted model for the early earth atmosphere, can be supported for the primordial existence of cyanomethanol.

Conclusions 2

• Polymerization of polypeptide from the monomer cyanomethanol is proposed.

• Enthalpic thermodynamic feasibility occurs for either mechanism, with amide formation providing product stability.

• It is concluded that cyanomethanol polymerization should be considered as a serious alternative to aminoacid condensation for the mechanism of primordial polypeptide (protein backbone ) formation.

Thank you for your attention