Mechanism and prebiotic synthesis of purine and pyrimidine deoxyribonucleoside mono-, di-, and triphosphates

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1975

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Abstract

Purine and pyrimidine deoxyribonucleosides mono-, di-, and triphosphates were synthesized in experiments simulating the drying of primitive lakes or pools by heating in open tubes aqueous solutions of dexoyribonucleosides, cyanamide or urea, and phosphate (sodium dihydrogen phosphate, diammonium hydrogen phosphate, or ammonium dihydrogen phosphate). When the more insoluble mineral phosphates (struvite, hydroxyapatite, or fluorapatite) were used (together with an agent, ammonium oxalate, to increase their solubility) in the reaction only monophosphate ester bonds were formed. However, pyrophosphate and polyphosphate ester bonds were formed if multi-step reactions were carried out, i.e., deoxyribonucleoside monophosphate was formed and phosphorylated to deoxyribonucleoside diphosphate, deoxyribonucleoside diphosphate was phosphorylated to deoxyribonucleoside triphosphate. As a result of all the aforementioned studies a step-by-step condensation mechanism was postulated for the phosphorylation of purine and pyrimidine deoxyribonucleosides. The synthesis of purine and pyrimidine deoxyribonucleoside triphosphates under presumed prebiotic condition was found to be affected most by three factors--reaction conditions, source of phosphate, and condensation agent. For optimum results the reaction should be carried out under drying conditions at 80[degrees] or 90[degrees] using sodium dihydrogen phosphate or diammonium phosphate as the phosphate source, and cyanamide as the condensation agent. There appears to be no single optimum pH values but instead optimum pH ranges. The effects of pH may be summarized as follows: Cyanamide catalyzed the synthesis of deoxyadenosine mono-, di-, and triphosphates between pH 4 and 8 and the synthesis of deoxyguanosine mono-, di-, and triphosphates between pH 5 and 9. For the pyrimidine deoxyribonucleosides, cyanamide catalyzed the synthesis of deoxycytidine mono-, di-, and triphosphates between pH 5 and 7 and the synthesis of thymidine mono-, di-, and triphosphates between pH 4 and 8. In addition urea catalyzed the synthesis of deoxycytidine mono-, di-, and triphosphates between pH 5 and 7. Guanidine, hydroxylamine, lysine, arginine, and histidine were found to be condensing agents for the synthesis of purine and pyrimidine deoxyribonucleotides. These are weak condensing agents in the class with imidazole and form only ordinary phosphate monoester bonds. The effect of conditions, i.e. phosphorylation occurring better during the final stages of evaporation ("semi-dry" or "evaporative state") than in dulute solution ("dilute solution" or "wet state") and at higher temperatures, and condensation agents (weak vs. strong) on the synthesis of deoxyribonucleotides may be explained by the different amounts of energy necessary to form a regular phosphate monoester bond (~3 Kcals/mole) and a pyrophosphate bond (~7 Kcals/mole). Thus only cyanamide and urea, as well as relatively high temperatures (~v90[degrees]C) and semi-dry conditions are good to form pyrophosphate bonds (to bring about a pyrophosphorylation condensation). The other weaker condensing agents, as well as the relatively dilute solutions and low temperatures (~60[degrees]C) are only capable of forming ordinary phosphate ester bonds.

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