474 Annals New York Academy of Sciences 



mechanism of adenine synthesis is supposed to be initiated by the base catalyzed 

 polymerization of hydrogen cyanide into nitriles.^^- The role played by am- 

 monia in this synthesis is 2-fold. It acts as a basic catalyst and it causes the 

 ammonolysisof hydrogen cyanide into formamidine and of nitriles into amidines. 

 One of the resuhing nitriles, possibly aminomalonodinitrile, condenses either 

 directly or after transformation to its mono- or diamidine with formamidine to 

 form AICAI. In the last step, AICAI condenses with another mole of formami- 

 dine to yield adenine. This last step has been confirmed in a separate experi- 

 ment in our laboratory. ^^^ 



The other purines were postulated to be formed from 4-aminoimidazole-5- 

 carboxamide.^^^ Recent experiments in our laboratory have confirmed this 

 assumption. 1^* It has been observed that AICA and guanidine condense in 

 aqueous ammonia systems to yield guanine. Moreover, when AICA is allowed 

 to react with urea under similar conditions, guanine and xanthine are formed. '^^ 

 The formation of the 1-carbon reactants, guanidine and urea, in the absence of 

 free oxygen, poses no special problem because compounds of this oxidation 

 level, such as urea, were detected by Miller, ^^ Berger,^* and Palm and Cal- 

 vin,^^ in their respective experiments with electric discharges, high energy 

 protons, and high energy electrons, which were carried under reducing condi- 

 tions. Other workers have also observed the formation of guanidine^^- and 

 urea^^^'^^^'^^^ from cyanides, cyanogen, or cyanates. 



The above experiments on the synthesis of adenine from mixtures of hydrogen 

 cyanide, ammonia, and water have been confirmed by Lowe et al}^^ who have 

 found an additional purine, hypoxanthine, among the reaction products. A 

 significant extension of these experiments has been carried out recently by 

 Calvin, ^^ and Palm and Calvin," who have observed the formation of adenine 

 by irradiating with 5 MeV electrons a mixture containing methane, ammonia, 

 and water among other reduced compounds. In summary, it seems to be well 

 established that the 4 major biological purines can be synthesized, from very 

 simple precursors, in aqueous systems under possible primitive Earth conditions. 



From a historical point of view, it should be said that at the turn of the last 

 century, cyanogen^^^ and hydrocyanic acid^^^'^^^ were thought to be involved in 

 the synthesis of proteins and purines in living organisms. These have since 

 been found to be erroneous concepts. Nevertheless, it is of interest that such 

 early ideas may apply to the abiogenic formation of these compounds. Studies 

 on the polymerization of hydrocyanic acid were initially carried out more than 

 150 years ago,'^- and, therefore, it is highly probable that purines, purine inter- 

 mediates, and other compounds of biological significance were synthesized in 

 the laboratory many times since then, yet have remained unidentified until the 

 present time. Interesting observations bearing on the synthesis of purines from 

 hydrogen cyanide were made by Gautier,''"* Fischer,'*'' Salomone,^'" and Johnson 

 and Nicolet,'*- and they are discussed in some detail in a recent paper from our 

 laboratory.'^' Aside from these early unsuccessful attempts on the synthesis 

 of purines from hydrogen cyanide, it should be added that uric acid was syn- 

 thesized from glycine and urea by Horbaczewski,''*^ and purine from formamide 

 and other simple compounds by Bredereck et «/.'■" '^^ However, none of the 

 biochemical purines found in nucleic acids was isolated or identified in these 

 experiments. 



