Cyanosulfidic prebiotic synthesis

Cyanosulfidic prebiotic synthesis is a proposed mechanism for the origin of the key chemical building blocks of life. It involves a systems chemistry approach to synthesize the precursors of amino acids, ribonucleotides, and lipids using the same starting reagents and largely the same plausible early Earth conditions. Cyanosulfidic prebotic synthesis was developed by John Sutherland and co-workers at the Laboratory of Molecular Biology in Cambridge, England.

Challenges
Prebiotic synthesis of amino acids, nucleobases, lipids, and other building blocks of protocells and metabolisms is still poorly understood. Proposed reactions that produce individual components such as the Strecker synthesis of amino acids, the formose reaction for the production of sugars, and prebiotic syntheses for the production of nucleobases. These syntheses often rely on different starting reagents, different conditions (temperature, pH, catalysts, etc.), and often will interfere with each other. These challenges have made determining the conditions for the origin of life difficult. Researchers have turned to systems chemistry type approaches to help overcome some of these challenges. Systems chemistry approaches form multiple products form a single synthesis under the same conditions and tend to be more similar to biological processes in that they have emergent properties, self-organization, and autocatalysis. Cyanosulfidic prebiotic synthesis is a systems chemistry approach.

Mechanism
The starting reactants for these reactions are hydrogen cyanide (HCN) as well as HCN derivatives and acetylene. Both of these are hypothesized to be present on the early Earth. The conditions this reaction occurs in are a relatively moderate temperature of 35 degrees C and in anoxic or oxygen free conditions. The early Earth was anoxic before the great oxidation event, making these conditions plausible. In the laboratory synthesis, a neutral phosphate buffer was used to maintain a stable, neutral pH. hydrogen sulfide (H2S) is used as a reductant in these reactions. The reactions are driven forward by ultraviolet radiation and catalyzed by Cu(I)-Cu(II) photoredox cycling. Some compounds in the system perform multiple roles. For example, phosphate serves as a buffer to maintain a neutral pH, acts as a catalyst in the synthesis of 2-aminooxazole and urea and serves as a reagent in the formation of glycerol-3-phosphate and ribonucleotides. The mechanisms involved in these reactions include reductive homologation processes to build larger, more complex molecules from the simple starting materials. The products of this reaction include the precursors of many amino acids, the precursors of lipids, and ribonucleotides. It is worth noting that most of the prebiotic monomers are not synthesized in their entirety by these reactions, only their precursors. The amino acid precursors would then be produced by Strecker synthesis reactions. Cyanosulfidic metabolism also does produce the precursors of both purines and pyrimidines ribonucleotides simultaneously. Many of the compounds produced also include intermediates in one-carbon metabolism.

Geochemical context
Sutherland and collaborators proposed a geochemical scenario to argue that cyanosulfidic synthesis was a plausible process on the early Earth. Their scenario starts following a meteorite impact leads to the production of HCN and phosphate. The meteorite fragments also supply the necessary sulfide for the reaction. As ponds and lakes containing these reagents experience wet dry cycles, ferrocyanide, sodium, and potassium salts precipitate out of solution into evaporites, concentrating and storing reactants for future chemistry. These evaporites can then be thermally altered through additional impacts or geothermal heating, producing all necessary components for the proposed syntheses. Rain and runoff create streams that transport compounds along geochemical gradients, introducing new reactants along the way which causes new syntheses to occur. The streams are also exposed to ultraviolet radiation, providing energy for the reactions. The conditions described here support an evaporative lake or terrestrial hydrothermal pond scenario for the origin of life. The proposed geochemical scenario also relies on flow chemistry concepts to introduce new reactants throughout the process to cause additional chemical reactions and syntheses to occur.

Limitations
Cyanosulfidic chemistry has several limitations. While the products are all formed from the same starting materials, many of the reactions require the periodic delivery of new reagents which complicates the syntheses. The chemical synthesis is therefore not truly “one-pot” chemistry which would require all reactants to be provided at the beginning which no further alterations. Sutherland and colleagues argue that a “flow-chemistry” approach featuring the movement of compounds through a stream experiencing different geochemical conditions makes their proposed system plausible.

Variants
Other challenges of the cyanosulfidic prebiotic synthesis approach is that the reductant, sulfide, has low solubility in water except in alkaline conditions and the main catalyst, copper, has a relatively low abundance in Earth’s crust. To address these problems, an alternative scheme for prebiotic systems chemistry called cyanosulfitic prebiotic synthesis has been proposed. These set of reactions relies on sulfite instead of sulfide, and ferrocyanide to catalyze reactions when exposed to ultraviolet light. The products of these reactions rely on similar chemistry to cyanofidic mechanisms such as reductive homologation and produce similar products such as amino acid precursors as well as sugars and hydroxy acids. Both sulfite (from sulfur dioxide released by volcanos) and ferrous iron (FeII) are hypothesized to have been present in high quantities on the early Earth, suggesting that this is potentially a much for feasible set of reactions.