Nucleoside and deoxynucleoside phosphorylation in formamide solutions

Abstract

Nucleosides or deoxynucleosides were converted to a number of phosphorylated nucleotide and deoxynucleotide derivatives by ammonium of alkali dihydrogen phosphates in formamide. Conversions were smaller and slower at room temperature and greater and faster at elevated temperatures. Nucleotides afforded product mixtures to those obtained for nucleosides under the same conditions, indicating the occurrence of transphosphorylation processes. Products of the reaction at elevated temperatures were cyclic nucleotides, nucleoside monophosphates, nucleoside diphosphates and cyclic nucleotide phosphates. The relative amounts of products formed were quite temperature dependent. Cyclic nucleotides were found to be in greatest abundance for reactions run at 125 degree or above. Relative yields of 2',3' and 5' nucleotides and 3' and 5' deoxynucleotides from several experiments are reported. 5'Monophosphates were generally found to be present in larger quantities than 2' or 3' monophosphates. 2'-Deoxyadenosine showed a preference for phosphorylation at the 3' position. Conclusion reached from mechanistic studies are that the phosphorylations are a series of equilibrium reactions, with cyclic nucleotides being formed irreversibly.

Origin of Informational Polymers

“…cannot be answered until the chemistry of the formation of the phosphoester bond has been understood, possibly based on easily available inorganic phosphates. Evidence that formamide does favor phosphoester bond formation in abiotic conditions has been reported (42). Formamide also allows full solubility of the otherwise weakly soluble deoxyadenosine (43).…”

Origin of first cells at terrestrial, anoxic geothermal fields

“…Some of the most successful attempts to simulate primitive abiogenic reactions have been conducted under conditions that are compatible with reconstructed conditions at the geothermal fields of the anoxic Earth. These promising experiments include syntheses of biologically relevant compounds in formamide solutions (98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108)(111)(112)(113)(114)(115), photosynthesis/photoselection of natural nucleotides (120)(121)(122)133), montmorillonite-catalyzed formation of long RNA oligomers (118) and membrane vesicles (134), RNA polymerization in the eutectic phase in water-ice (135), abiotic UV photosynthesis of the tricarboxylic acid cycle intermediates at ZnS (83,84) and TiO 2 crystals (136), as well as UV-triggered recharging of ADP to ATP (137). Further experimental exploration of models that mimic the conditions at anoxic geothermal fields are expected to shed more light on precellular evolution.…”

“…Specifically, the wetted surfaces would undergo continuous drying resulting in selective accumulation of the least volatile compounds, which, in this case, would be simple amides, with boiling points of approximately 200°C due to their ability to form strong hydrogen bonds. Formamide, the likely key building block for abiotic synthesis of nucleotides and amino acids (98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108), could form via hydrolysis of hydrogen cyanide, which is found in volcanic gases and in exhalations of geothermal fields (109). In addition, elimination of a water molecule from ammonia salts of carboxylic acids could also yield amides, in particular, formamide from ammonia formate.…”

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.…”