Abiotic Regioselective Phosphorylation of Adenosine with Borate in Formamide

Abstract

Nearly 40 years ago, Schoffstall and his coworkers used formamide as a solvent to permit the phosphorylation of nucleosides by inorganic phosphate to give nucleoside phosphates, which (due to their thermodynamic instability with respect to hydrolysis) cannot be easily created in water by an analogous phosphorylation (the "water problem" in prebiotic chemistry). More recently, we showed that borate could stabilize certain carbohydrates against degradation (the "asphalt problem"). Here, we combine the two concepts to show that borate can work in formamide to guide the reactivity of nucleosides under conditions where they are phosphorylated. Specifically, reaction of adenosine in formamide with inorganic phosphate and pyrophosphate in the presence of borate gives adenosine-5'-phosphate as the only detectable phosphorylated product, with formylation (as opposed to hydrolysis) being the competing reaction.

Evaporite Borate‐Containing Mineral Ensembles Make Phosphate Available and Regiospecifically Phosphorylate Ribonucleosides: Borate as a Multifaceted Problem Solver in Prebiotic Chemistry

“…[20] Formamide and urea are suitable media for the formation of hydrolytically unstable phosphate esters from inorganic phosphate; [21,22] formamide is also an excellent precusor for nucleobases. [23,24] Missing here, however, is a discussion of the phosphate problem.…”

Emergence of the First Catalytic Oligonucleotides in a Formamide‐Based Origin Scenario

“…Furukawa et al. report that in the presence of borate minerals the phosphorylation in formamide selectively leads to adenosine‐5′‐phosphate . This result is especially important since a recent study suggests that under hydrothermal conditions a mixture of 5′‐AMP and 5′‐UMP can be efficiently oligomerized nonenzymatically without further activation of the phosphate group in the form of phosphoimidazolides…”

Nucleobase and amino acid formation through impacts of meteorites on the early ocean

“…Formamide formation would have been possible on the early Earth, but it would have been difficult for formamide to accumulate to high enough concentrations to facilitate the synthesis of nucleobases in oceanic environments (Miyakawa et al, 2002b). One potential process to concentrate formamide in aqueous solutions is fractional distillation, but this is only possible in land-based systems (Furukawa et al, 2015). A large amount of geological evidence suggests that there were smaller amounts of land area on the early Earth (Armstrong and Harmon, 1981;McCulloch and Bennett, 1994).…”