Prebiotic Syntheses of Nucleobases

Only a few years after the Miller-Urey experiment was published, J. Oro was able to synthesize one of the most important biomolecules, adenine. This purine derivative is not only a component of the nucleic acids, but as ATP, adenosine triphosphate (in combination with ribose and three phosphate residues), it plays a key role in the metabolism of all living creatures. The chemical formula of adenine is C5H5N5, or expressed in another way, (HCN)s. 

It has been known for many years that hydrocyanic acid molecules are found in interstellar space and in the tails of comets. The question thus arises as to whether there is a connection between the immense importance of adenine in living beings and the occurrence in the cosmos of a building block for its formation. 

Pullman showed more than 40 years ago, the purine base adenine occupies a unique situation in the purine family in comparison to the other purines, it has the greatest resonance energy per -electron, i.e., it is more stable, and thus likely to have been incorporated preferentially into biomolecules (Pullman, 1972). 

Oro s experiment (Oro, 1960) was very simple he heated ammonium cyanide to 343 K and was able to detect adenine after a few days. Shortly afterwards, he showed that five molecules of HCN combined to give one of adenine (Oro, 1961). An intermediate, aminomalonitrile, can be converted to 4-aminoimidazole-5-carboxamide in two different ways (Sanchez et al., 1966a, b) (Fig. 4.4)  

The hydrolysis leads to 4-aminoimidazole-5-carboxamide, which under certain conditions can react with various partners (e.g., HCN, dicyan or formamidine) to give purines (i.e., adenine, guanine, hypoxanthine and diaminopurine). 

---

Until the 1980s, yields of nucleobases obtained in prebiotic syntheses were very small. Thus, some scientists assumed that in earlier phases of molecular evolution, the nucleic acids used other bases in their information-transmitting substances. Piccirilli et al. (1990) suggested isocytosine and diaminopyridine, while Wachtershauser (1988) suggested that the first genetic material possibly consisted only of purines. However, pyrimidine (about a fifth of the total amount of purines present) had been detected in the Murchison meteorite, so that an effective pyrimidine synthesis should have been possible. 

Formamide is itself hydrolyzed by water, meaning that it persists only in a relatively dry environment, such as a desert. Desert environments recently proposed as being potential sites for the prebiotic synthesis of ribose18 may hold formamide as well. Since formamide boils at —400 K, a mixture of formamide and water, if placed in the desert, would lose its water over time and end up as a pool of formamide. Within this pool, many syntheses are thermodynamically favorable polypeptides from amino acids, nucleosides from sugars and bases, nucleotides from nucleosides and inorganic phosphate, and RNA from nucleotides. Indeed, phosphate esters are also spontaneously synthesized. This includes ATP (from ADP and inorganic phosphate), nucleosides (from ribose borates and nucleobases), peptides (from amino acids), and others.19-21... 

---