Illuminating Life's Origins: UV Photochemistry in Abiotic Synthesis of Biomolecules

Abstract

Solar radiation is the principal source of energy available to Earth and has unmatched potential for the synthesis of organic material from primordial molecular building blocks. As well as providing the energy for photochemical synthesis of (proto)biomolecules of interest in origins of life-related research, light has also been found to often provide remarkable selectivity in these processes, for molecules that function in extant biology and against those that do not. As such, light is heavily implicated as an environmental input on the nascent Earth that was important for the emergence of complex yet selective chemical systems underpinning life. Reactivity and selectivity in photochemical prebiotic synthesis are discussed, as are their implications for origins of life scenarios and their plausibility, and the future directions of this research.

Scheme 1. Reaction Pathways of Polymerizing Hydrogen Cyanide, and Stabilities of Intermediates, Primarily Elucidated by Orgel et al.,⁻ and the Photochemical Mechanism of Rearrangement of DAMN 2 to AICN 9 Proposed by Barbatti et al.

Scheme 2. Reductive Homologation of HCN 1 with Photochemically (254 nm) Generated, Hydrated Electrons Furnishes the Precursors of Simple Sugars, Amino Acids, and Membranes

Hydrated electrons (or hydrogen atoms derived therefrom by protonation) can be generated by: photoredox cycling of Cu(II) and Cu(I) cyanocuprates, with the stoichiometric reductant being HCN 1 (top left); photoredox cycling of Cu(II) and Cu(I) complexes of cyanide, sulfide, and thiocyanate, with the stoichiometric reductant being H₂S (top middle); or photoredox cycling of Fe(III)–Fe(II), with sulfite being the stoichiometric reductant (top right). Similar reductive conditions produce thymine and deoxyribose (bottom left and bottom right, respectively). Reaction conditions indicating reaction of an electron can be promoted by more than one of the photoreductive cycles at top.

Scheme 3. Selective Prebiotic Synthesis of Pyrimidine Ribonucleosides and Purine Deoxyribonucleosides Driven by UV Irradiation

Non-canonical regioisomers are depicted in gray. Reactions are performed in water unless dry state or formamide (HCONH₂) is indicated. Ade = adenine, P_i = inorganic phosphate.

Scheme 4. Proposed Mechanism of the Photoanomerization of 50/51

Scheme 5. Proposed Mechanism of Photoreduction of Thioanhydrouridine 61 with Hydrosulfide to 2′-Deoxy-2-thiouridine 60, Proceeding via a Radical Anion Intermediate 72

Scheme 6. Proposed Mechanism of Photoreduction for Thioanhydroadenosines with Bisulfite or Hydrosulfide, and C8–S Photoreduction of the Products Generated and Related Nucleosides

Photoreduction with bisulfite may proceed via competing mechanisms in (a) and (b). In (a), photolysis of the thioanhydronucleoside occurs before reduction, providing different intermediates in the reduction of N⁹-thioanhydroadenosine 62 and N⁷-thioanhydroadenosine 63, and thus different outcomes. In (b), reduction of 62 and 63 is effected by a photochemically generated hydrated electron, resulting in different radical anion intermediates and different reaction outcomes. (c) Stable encounter complexes of the thioanhydroadenosines and hydrosulfide such as 77 were calculated, and allow the reduction to proceed for regioisomers 62 and 62 in a similar fashion, with radical anion 75 and its N⁷-regioisomer as intermediates (mechanism for 63 not shown). (d) Photoreduction (300 nm) of 67a to generate 64a presumably proceeds via the mechanism calculated by Powner et al. for related ribo- and arabino-8-mercaptopurine nucleosides 67b–g. The yield of ribo- and ara-inosine (64f and 64g) was low because of a competitive photodecomposition pathway via 80. CT = charge transfer.

Scheme 7. Activating Agents, Such as Methyl Isonitrile 81, Allow the Conjoining of Monomers via Reactive Groups That May Be Dehydrated, Such as Phosphate Monoesters and Carboxylic Acids, and Partner Nucleophiles Such as Amines or Alcohols, Leading to Oligomeric Species Such as Nucleic Acids, Peptidyl-RNA, and Peptides

New bonds and dehydrated water molecule are shown in blue.

Scheme 8. Prebiotically Plausible Photochemical Synthesis of Methyl Isonitrile 81

In summary, ferrocyanide 83 undergoes photoaquation to form transient complex 85, which undergoes ligand substitution of water with nitrite to ultimately form nitroprusside 87. Nitroprusside 87 reacts with methylamine 89 to form alkylating species 88, reaction of which with ferrocyanide forms isonitrile complex 86. Irradiation of 86 in the presence of a displacing ligand such as cyanide provides methyl isonitrile 81.

Scheme 9. Various Methods of Activating Phosphate and Carboxylate Groups

(a) The Passerini reaction is an efficient method to activate phosphate monoesters; however, carboxylates rearrange intramolecularly once activated. (b) Methyl isonitrile 81 in combination with DCI 101 facilitates both phosphate and carboxylate group activation; thus, upon activation at moderately low pH, a mixture of nucleoside phosphates and (acyl)amino acids provided peptides, mixed anhydrides, and aminoacyl RNA. (c) The DCI/methylisonitrile-mediated condensation activates amino acids to form racemizing intermediates 110, which, for acetylalanine 104, are partially resolved by A3′P. AMP = adenosine 5′-monophosphate. Ade = N9-adenyl.

Scheme 10. Photochemical Input Will Act to Synthesise and Destroy Molecules—The Chemical Evolution of Prebiotic Mixtures, Based on Mixture-Variable Rates of Synthesis and Destruction, Could Present an Explanation for the Preponderance in Biology of Typically Photostable, Canonical Biomolecules

Scheme 11. An Example of Photochemical Stability Placing a Constraint on the Prebiotic Scenario

In this case, the photochemical stability of 113 is low compared to its forward reaction rate in the sequence, thereby imposing concentration minima or sunscreening mechanisms on the scenario.