ARTICLES
sort of combination of the syntheses is required. However, trying to topography of the basin floor and the solubilities of salts would
meld the various scenarios together has been very problematic have played major determining roles. Thus, the most-soluble salts,
because the chemistries are so different, and this is one of the such as sodium and potassium chloride, and mixed salts would
reasons that many in the field have assumed that one such have precipitated from the solution last, and thus been deposited
synthesis and associated subsystem came first. It was through in relatively small areas as the last pools in the depressions on the
analysis of these problems that we adopted the approach of basin floor dried out. Less-soluble salts and mixed salts would, pre-
attempting to delineate favoured reaction pathways that lead to sumably, have been deposited from larger bodies of water and thus
multiple biologically relevant compounds, and the reaction been spread over larger areas (Fig. 2b). When streams first reached
network that we present herein (Fig. 1) is the result of this the depressions on the basin floor that contained large amounts of
strategy. However, we had also originally hoped to be able to find sodium and potassium chloride, brine pools would have formed. If
conditions under which the whole network could operate in one the depressions, or the streams that first reached them, also con-
pot (our thinking being influenced by the previous syntheses), but tained copper ions and cyanide, then the formation of Nieuwland
our results now suggest that this would be difficult. Although the catalysts can easily be envisaged. Leaching of the products of
yields of the individual steps of the network are uniformly good high-temperature thermal metamorphosis of calcium ferrocyanide
to excellent (Tables 1 and 2), and several multistep reaction could then have supplied acetylene (32) for cross-coupling with
sequences still proceed in good yield in one pot, the key Kiliani– hydrogen cyanide (11). Copper(I) ions would have catalysed the
Fischer-type homologation chemistry requires the periodic synthesis of acrylonitrile (33) and thence 46 and 47, the α-aminoni-
delivery of hydrogen cyanide (11) and hydrogen sulfide (12), and trile precursors of arginine and proline (Fig. 1c). Copper(II) ions
there are several points in the network at which the sequential produced by the photooxidation of copper(I) ions would have pro-
delivery of other reagents is required. We therefore extended our moted the synthesis of cyanoacetylene (6) in the form of its solid-
thinking beyond traditional ‘one-pot’ chemistry and considered state copper(I) coordination compound, CuC3N. Further addition
other chemical synthesis formats, bearing in mind the need for of cyanide would have initiated the sequence of reactions that lead
compatibility with our outline geochemical scenario.
to 49 and 54, the α-aminonitrile precursors of asparagine and aspar-
tic acid, and glutamine and glutamic acid (Fig. 1d). Finally, synthesis
of anhydronucleoside 7, and thence the ribonucleotides 9 and 10,
could take place through the stream previously formed by the
merger of two tributaries (containing the pentose aminooxazoline
(5)) running into a pool that contained CuC3N.
Refinement of the geochemical scenario. One way in which 11 and
12 could be delivered periodically involves flow chemistry37, and we
quickly realized that this would be facile in a geochemical setting.
Thus, if the terrain onto which the evaporites were deposited and
thermally metamorphosed was not flat, then subsequent rainfall
would result in rivulets or streams flowing downhill to form pools
at depressions in the evaporite basin (Fig. 2d, left). Water flowing
over the products of the thermal metamorphosis of sodium or
potassium ferrocyanide would leach out highly soluble sodium or
potassium cyanide, and result in a concentrated cyanide solution,
which would then dissolve any metal sulfides the stream
encountered and liberate hydrosulfide. Solar ultraviolet irradiation
could then drive a first phase of the reduction chemistry, which
would pause when hydrogen cyanide and hydrosulfide in the
stream became depleted. Further passage of the solution over
ground that contained soluble cyanide salts and metal sulfides
could then initiate subsequent phases of the reduction chemistry
to result in homologation of the aldehydes produced in the first
phase. Additional reagents, such as phosphate, could also be
delivered at other points of the reaction network through the
Conclusions
Although it necessarily has to be painted with broad brushstrokes,
the picture that emerges is of an overall reaction network developing
over time in separate streams and pools, according to a dynamic
flow chemistry scheme. The various products would be synthesized
by subtle variations in the flow-chemistry history of the streams and
the order in which they merged or ran into pools. Although the
overall scheme would not involve all the steps of the reaction
network taking place simultaneously in ‘one pot’, the various pro-
ducts would end up mixed together in pools. Rather than invoking
fundamentally different scenarios and chemistries for the syntheses
of the molecular components of informational, compartment-
forming and metabolic subsystems, and then concluding that one
or other subsystem must have come first, we describe a scenario
in which variations on a chemical homologation theme result in
the components of all three subsystems being produced and then
blended together. The reliance of the homologation chemistry on
hydrogen cyanide (11) (all the carbon and nitrogen atoms in the
compounds of the reaction network derive from this single
source) and hydrogen sulfide (12) prompts us to use the term
‘cyanosulfidic’ to describe this protometabolic38 systems chemistry.
dissolution of evaporite salts.
A
geochemically plausible
refinement of the scenario suggests how convergent synthesis
could take place if streams with different flow chemistry histories
merged (Fig. 2d, right). Thus, if a stream in which the reductive
homologation chemistry had paused at the stage of glycolaldehyde
(1) (Fig. 1a) and passed over the thermally metamorphosed
products of calcium ferrocyanide, leaching out of cyanamide (2)
would lead to the synthesis of 2-aminooxazole (3).
Glycolaldehyde (1) in a similar stream that, instead, passed over
further ground containing cyanide and metal sulfides would be
homologated to give glyceraldehyde (4) by way of cyanohydrin
55. If the two streams subsequently merged, reaction of 3 and 4 at
the confluence would generate the pentose aminooxazolines,
including 5. If a stream in which glyceraldehyde (4) had been
Received 21 October 2014; accepted 9 February 2015;
published online 16 March 2015
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It is not possible to predict precisely where various ferrocyanides
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6
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