Synthesis of α-amino and α-hydroxy acids under volcanic conditions: implications for the origin of life

Article abstract of DOI:10.1016/j.tetlet.2009.12.084

Facile synthesis of α-hydroxy and α-amino acids is observed at temperatures from 145 to 280 °C with catalytic Ni²⁺, with cyano ligands as source for C and N, and with CO as a reductant and as a source for C. Implications for the problem of the origin of life are discussed.

Full text of DOI:10.1016/j.tetlet.2009.12.084

Tetrahedron Letters 51 (2010) 1069–1071
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of a-amino and a-hydroxy acids under volcanic conditions:
implications for the origin of life
Claudia Huber a, Wolfgang Eisenreich a, Günter Wächtershäuser b,c,
*
a Lehrstuhl für Biochemie, Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, D-85747 Garching, Germany
b Weinstraße 8, D-80333 München, Germany
c 209 Mill Race Dr., Chapel Hill, NC 27514, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Facile synthesis of
a-hydroxy and a-amino acids is observed at temperatures from 145 to 280 °C with
catalytic Ni2+, with cyano ligands as source for C and N, and with CO as a reductant and as a source
for C. Implications for the problem of the origin of life are discussed.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 5 November 2009
Revised 15 December 2009
Accepted 15 December 2009
Available online 22 December 2009
Keywords:
Nickel
Cyanide
Origin of life
Amino acids
Hydroxyl acids
Carbon monoxide
While temperature is the most pervasive physical parameter of
life, the thermal conditions of the origin and early evolution of life
remain unresolved. There are two main theories for the origin of
life on Earth: the prebiotic broth theory of a cold, oceanic, hetero-
trophic origin and the pioneer metabolic theory of a hot, volcanic,
chemo-autotrophic origin.1 Very low temperatures are considered
mandatory for the slow accumulation of a prebiotic broth for
chemical stability reasons, while the high-temperature synthesis
of amino acids under volcanic/hydrothermal conditions is claimed
to be too inefficient in an aqueous environment to compete with
thermal decomposition.2,3
as a source for catalytic nickel centers, 2 mmol KCN (variously la-
beled) for providing cyano ligands as a source for N and as a major
source for C, and with a CO gas phase as a reductant and as a minor
source for C. In comparative experiments, NiSO4 was replaced by
FeSO4 or CoSO4. Table 1 lists the variations of reaction conditions
and the three major families of organic products. In a typical run,
a 50 mL stainless steel laboratory autoclave (Roth) with glass insert
was charged with 0.5 g (6.75 mmol) of Ca(OH)2, 524 mg (2 mmol)
of NiSO4Á6H2O, 132 mg (2 mmol) of KCN, 10 mL of deaerated and
Ar-saturated water, and a gas phase of CO (CO 2.5 Air Liquide).
The gas pressure at room temperature was chosen so that the total
pressure given in Table 1 was reached at the stated reaction tem-
perature. The pH of the reaction mixture was measured at the
end of the stated reaction time. The reaction mixture was centri-
fuged and the supernatant was neutralized with 5 M HCl and
freeze-dried. The residue was derivatized with N-(tert-butyldi-
methyl-silyl)-N-methyl-trifluoroacetamide (TBDMS) in acetonitrile
(1 h at 80 °C) for analysis by GC–MS [Shimadzu GC-17A and QP-
5000; J&W Scientific DB-5 MS column (length: 30 m, I.D.
In the context of a hot volcanic origin, the aqueous reaction sys-
tem Ni(OH)2/KCN/CO under alkaline aqueous conditions was previ-
ously shown4 to produce
a-amino and a-hydroxy acids in the
moderate temperature range of 100 20 °C, which defines the hab-
itats of hyperthermophilic organisms. We now report an increase
of production efficiency by up to an order of magnitude, if the reac-
tion temperature is increased to the ultra-hyperthermophilic range
of 145–280 °C with an optimum around 160–180 °C. The increased
reaction temperature also allowed the detection of amides as reac-
tion intermediates.
We modeled volcanic/hydrothermal conditions by a low-pres-
sure, heterogeneous batch reaction system combining an aqueous
suspension of Ca(OH)2 as buffer in 10 mL water with 2 mmol NiSO4
0.25 mm, film: 0.25 lm); temperature program and settings: 0–
3 min at 90 °C, 3–22 min at 90–280 °C, 10 °C/min; 22–25 min at
280 °C; injector temperature: 260 °C; detector temperature:
260 °C; column flow rate: 1 ml/min; scan interval: 0.5 s; detector
voltage: 1.5 kV]. External standards were used for quantitation
with subtraction of small concentrations of 12C-lactate detected
in blind tests. Glyceramide has been synthesized5 and used for
identification, but not for quantitation because of isolation
* Corresponding author.
E-mail address: gwmunich@yahoo.com (G. Wächtershäuser).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.12.084

1070
C. Huber et al. / Tetrahedron Letters 51 (2010) 1069–1071
Table 1
Products of carbon fixation reactions under ultra-hyperthermophilic conditions
Run
1
2
3
4
5
6
7
8
9
10
11
Temperature (°C)
Reaction time (h)
KCN 2 mmol
100
20
145
20
160
5
160
10
160
20
160
40
180
20
200
20
280
5
160
20
160
20
12C14
65
N
12C14
60
N
12C14
55
N
13C14
55
N
12C15
55
N
13C14
55
N
13C14
50
N
12C14
40
N
13C14
30
N
13C14
7
N
13C14
1
N
pCO at rt (bar)
a
Total pressure (bar)
75
75
75
75
75
75
75
75
80
15
5
Ca(OH)2 g/10 mL
Final pH
0.5
12.7
0.5
12.8
0.5
12.9
0.5
12.8
0.5
12.6
0.5
9.1
0.5
12.6
0.5
6.5
1
12.8
0.5
12.7
0.5
12.9
Products
l
mol/10 mL (% 13Ct)b
g1 Glycolate
g2 Glycolamide
g3 Glycine
0.24
0.01
0.65
—
2.50
0.14
3.40
0.15
1.70
0.54
1.20
0.43
4.30
3.70
3.90
1.30
6.00
0.23
7.80
0.12
6.30 (92)
0.02
8.40 (97.5)
—
4.88
0.02
6.10
tr
4.40
0.03
3.40
—
2.70
—
0.24
—
2.60
—
2.90
—
0.63
—
0.91
—
g4 Glycinamide
P
G = 2 Á g/20c
a1 Lactate
0.09
0.62
0.37
1.32
1.42
1.47
1.10
0.78
0.29
0.55
0.15
0.08
—
—
0.21
0.02
0.24
0.02
0.03
0.01
0.03
0.01
0.23
0.13
0.16
0.13
0.55
0.02
0.86
0.01
0.80 (84)
—
1.00 (91)
—
0.46
—
0.84
—
0.37
—
0.50
—
0.30
—
0.03
—
0.11
—
0.11
—
0.06
—
0.03
—
a2 Lactamide
a3 Alanine
a4 Alaninamide
—
P
A = 3 Á a/20
s1 Glycerate
s2 Glyceramide
s3 Serine
0.01
0.07
0.01
0.1
0.22
0.27
0.2
0.13
0.05
0.03
0.01
—
—
—
—
0.75
tr
0.07
0.07
0.49
0.50
0.05
0.03
1.30
0.38
0.07
0.07
2.90
0.02
0.33
0.47
3.50 (98)
—
0.21 (94)
0.16 (96)
1.90
—
0.12
0.19
0.71
—
—
tr
—
—
—
0.35
—
—
—
—
—
—
s4 Isoserine
—
—
P
S = 3 Á s/20
—
0.13
0.16
0.27
0.56
0.58
0.33
0.11
—
0.05
—
a
b
c
p(H2O + CO) at reaction temperature; tr 0.002–0.005
lmol/10 mL; — <0.002
lmol/10 mL.
%
13Ct in run 6 = % totally 13C-labeled isotopomer (13C2 or 13C3).
g = g1 + g2 + g3 + g4; a = a1 + a2 + a3 + a4; s = s1 + s2 + s3 + s4; G, A, S = % cyanide-C entering pathways to Gly, Ala, Ser product family.
P
P
P
difficulties. The quantity of glyceramide was estimated by assum-
ing the same peak intensity ratio for glycerate:glyceramide as for
lactate:lactamide.
Table 1 lists the three main organic product families: G = Gly-
family (glycolate, glycolamide, glycine, glycinamide); A = Ala-fam-
ily (lactate, lactamide, alanine, alaninamide); S = Ser-family (gly-
cerate, glyceramide, serine, isoserine). The yields in
lmol are
stated as concentrations in the 10 mL water phase of the reaction
system. For the representative example of run 6, the ratios of to-
tally 13C-labeled products to the sums of all isotopologues [13C2/
(
13C2 + 13C12C + 12C2) for C2-products and 13C3/(13C3 + 13C212C +
13C12C2 + 12C3) for C3-products] have been determined by SIM
mode and stated as % values. It is apparent that the cyano ligands
are the main C-source for the carbon skeletons of the products. The
global yield for each product family relative to the cyano carbon
atoms is stated, whereby the minor contribution by CO as C-source
is not subtracted. The reaction rates depend on the activities of dis-
solved CO, which are quite low at the high reaction temperatures
and at the pressures that were chosen for technical reasons. In case
of geologically more realistic higher pressures, the reaction rates
are expected to be significantly higher.6 In repeats of run 5 with
Figure 1. Temperature dependence of the global yields of
glycolate + lactate + glycerate (dashed line) and of -amino acids: glycine + ala-
nine + serine + isoserine (solid line) in runs 1, 2, 5, 7, 8.
a-hydroxy acids:
Co (or Fe) instead of Ni, we obtained 0.7 (or 0.04)
lmol/10 mL gly-
a
colate, 0.2 (or 0.06)
alanine.
lmol/10 mL glycine, and traces of lactate and
We plotted the temperature dependence of the sum of all
a-hy-
the yield decrease with decreasing CO pressure (run 1 vs runs 10
and 11).
droxy acid yields and of the sum of all -amino acid yields of runs
a
1, 2, 5, 7, 8 (Fig. 1). The striking similarity of the overall shapes of
the two graphs, both with maxima between 160 °C and 180 °C sig-
nifies a closely interconnected system of competitive pathways.
The steep drop of the yield beyond 160 °C is mainly attributed to
the decrease of the ratio of the partial pressure of CO to the partial
pressure of H2O. The reactions are amazingly specific considering
the high reaction temperatures, which may be due to the ligand
nature of the source for C and N. It is remarkable that the yield in-
crease with increasing temperature is sufficient to overcompensate
Variation of the reaction time from 5 h to 40 h (runs 3–6) shows
that the concentrations of all
throughout the 40 h reaction time, with the exception of serine and
isoserine, which drop after 20 h. This reflects the stability of the
hydroxy and -amino acids under our reaction conditions. Even ser-
a-hydroxy and a-amino acids increase
a-
a
ine and isoserineare surprisingly stable in spite of the b-hydroxyand
b-amino groups. Moreover, runs 3–6 show that the amides are
formed as intermediates, which yield the free a-hydroxy acids and

C. Huber et al. / Tetrahedron Letters 51 (2010) 1069–1071
1071
a
-amino acids by hydrolysis. This means that the amides are avail-
of CO is related to the function of anaerobic carbon monoxide
dehydrogenase, a nickel enzyme and the reaction products are
essential constituents of extant metabolisms.
We anticipate our results to be the starting point for a program
of reaction-chromatographic evolution experiments that model
volcanic flow conditions by a pressurized flow reactor with a cata-
lytic mineral bed as stationary phase and with pH and temperature
gradients along the flow path.9,10
able as activated products for further metabolic reactions in compe-
tition with hydrolysis. In some runs, the increased productivity at
higher temperatures allowed the detection of the carbamates of gly-
cine and alanine with CO-derived carbamate groups. Hydantoin as
activated derivative of glycine was detected in runs 3 and 4 as dou-
ble- and triple-silylated derivatives. Hydantoin is structurally re-
lated to the imidazole ring of uric acid, a purine. In run 4 the
hydantoin was formed as 13C2-isotopomer, which indicates that
hydantoin forms from glycine amide by ring formation with CO.
The mechanism would be analogous to the transformation of a pep-
tide into a peptide derivative with an N-terminal hydantoin ring in
the presence of CO and Ni-catalysts as seen in the peptide cycle.7
Our results have implications for the problem of the origin of
life. They confirm volcanic/hydrothermal sites as efficient sources
Acknowledgments
This work was funded by the Deutsche Forschungsgemeinschaft.
We thank A. Bacher and M. Groll for providing the laboratory facili-
ties and for generous support.
for
a-hydroxy acids and
a-amino acids. Moreover, by reflecting a
References and notes
potential hadean chemistry they lend support for a much earlier
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heterotrophic origin of life in a prebiotic broth the demonstrated
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volcanic gases and a stationary phase of hadean ultramafic rocks.
Specifically, our results allow to locate the beginning of organic
synthesis in flow zones with temperatures as high as 280 °C. The
evolutionary relevance of our reactions is underscored by their
analogy with extant biochemistry. Notably, the reducing function
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