Transcript A Novel Approach to Prebiotic Protein Synthesis

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
iminoaceticpropionic 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 DiOxygen
Atomic
2Px
2Py
Molecular
Atomic
s*
p*
p*
p
p
2Pz
2Pz
2Py
s
E
s*
2S
s
2S
s*
1S
1S
s
2Px
1O
and 3O2 with Linoleic Acid
2
Absorbance at 233 nm
1.6
1.2
1
O2
0.8
0.4
3
O2
0
200
400
600
800
Reaction Time in Minutes
1,000
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
O
║
C ─ OH
H─N─C
H
90
98.8
188.8
Forming Energy
O
║
C ─ NH
H ─ OH
TOTALS
92.8
117.5
210.3
Bond Energies of Cyanomethanol
Polymerization (kcal/mole)
•
•
•
•
Breaking Energy
H2C ─ OH
90
NΞC ─ CH2 212.6
CH2O ─ H 101.5
•
H2C ─ NH
72.8
amide resonance 20.0
•
•
Forming Energy
O═C
176
O ═ C ─ NH 72.8
N─H
98.8
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