DIMERIZATION IN HIGHLY CONCENTRATED-SOLUTIONS OF PHOSPHOIMIDAZOLIDE ACTIVATED MONONUCLEOTIDES

Phosphoimidazolide activated ribomononucleotides (pN) are useful subs trates for the non-enzymatic synthesis of polynucleotides. However, di lute neutral aqueous solutions of pN typically yield small amounts of dimers and traces of polymers; most of pN hydrolyzes to yield nucleo side 5'-monophosphate. Here we report the self-condensation of nucleos ide 5'-phosphate 2-methylimidazolide (2-MeImpN with N = cytidine, urid ine or guanosine) in the presence of Mg2+ in concentrated solutions, s uch as might have been found in an evaporating lagoon on prebiotic Ear th. The product distribution indicates that oligomerization is favored at the expense of hydrolysis. At 1.0 M, 2-MeImpU and 2-MeImpC produce about 65% of oligomers including 4% of the 3',5'-linked dimer. Examin ation of the product distribution of the three isomeric dimers in a se lf-condensation allows identification of reaction pathways that lead t o dimer formation. Condensations in a concentrated mixture of all thre e nucleotides (U,C,G mixtures) is made possible by the enhanced solubi lity of 2-MeImpG in such mixtures. Although percent yield of internucl eotide licked dimers is enhanced as a function of initial monomer conc entration, pyrophosphate dimer yields remain practically unchanged at about 20% for 2-MeImpU, 16% for 2-MeImpC and 25% of the total pyrophos phate in the U,C,G mixtures. The efficiency by which oligomers are pro duced in these concentrated solutions makes the evaporating lagoon sce nario a potentially interesting medium for the prebiotic synthesis of dimers and short RNAs.