Our previous kinetic and thermodynamic studies upon the reactional system HCHO/HCN/NH3 in aqueous solutions are completed. In the assumed prebiotic conditions of the primitive earth ([HCHO] and [HCN] near 1 g L-1, T = 25 degrees C, pH = 8, [NH3] very low), this system leads to 99.9% of alpha-hydroxyacetonitrile and 0.1% of alpha-aminoacetonitrile (precursor of the alpha-amino acid). The classical base-catalyzed hydration of nitriles, slow and not selective, can not modify significantly this proportion. On the contrary, we found two specific and efficient reactions of alpha-aminonitriles which shift the initial equilibrium in favor of the alpha-aminonitrile pathway. The first reaction catalyzed by formaldehyde generates alpha-aminoamides, precursors of alpha-aminoacids. The second reaction catalyzed by carbon dioxide affords hydantoins, precursors of N-carbamoyl-alpha-aminoacids. In the primitive hydrosphere, where the concentration in carbon dioxide was estimated to be higher than that of formaldehyde, the formation of hydantoins was consequently more efficient. The rates of hydrolysis of the alpha-aminoacetamide and of the hydantoin at pH 8 being very similar, the synthesis of the N-carbamoyl-alpha-amino acid seems then to be the fatal issue of the HCHO/HCN/NH3 system that nature used to perform its evolution. These N-protected alpha-amino acids offer new perspectives in prebiotic chemistry, in particular for the emergence of peptides on the prebiotic earth.

Alpha-N-Carbamoyl amino acid (CAA), whose conditions of formation in a prebiotic hydrosphere have been described previously (Taillades et al. 1998), could have been an important intermediate in prebiotic peptide synthesis through reaction with atmospheric NOx. Nitrosation of solid CAA (glycine or valine derivative) by a 4/1 NO/O2 gaseous mixture (1 atm) yields N-carboxyanhydride (NCA) quantitatively in less than 1 h at room temperature. The crude solid NCA undergoes quantitative oligomerization (from trimer to nonamer under the conditions we used) when treated with a (bi)carbonate aqueous buffer at pH 9. We therefore suggest that part of the prebiotic amino acid activation/polymerization process may have taken place in a dry phase ("drying-lagoon" scenario).

Recent developments in peptide synthesis have underlined the importance of optimising, on a preparative scale, the N-carbamoylation of amino acids by aqueous cyanate. To this purpose, a theoretical model of aqueous cyanate reactivity was designed. The parameters of the model were evaluated, for various pH and temperatures, from a critical survey of the literature, together with additional experimental data. Computer-simulated kinetics based on this model showed the reaction efficiency to be significantly dependent on pH, and suggested optimum conditions to be moderate temperatures and pH 8.5-9. Discussion of the practical convenience of these theoretical results led us to prefer 40-50 ЊC and a pH range of 7-8 as reaction conditions, thus maintaining reaction times within a few hours. Various N-carbamoyl amino acids (ureido derivatives of glycine, -valine, -alanine, -leucine, -methionine, N ε -trifluoroacetyl--lysine, β-alanine) were thus successfully synthesised on the gram to kilogram scales.

Our work aims to propose a new hypothesis for the prebiotic formation of ot-aminoacids and peptides. In a first part, we present kinetic and thermodynamic studies upon the equilibria between the prebiotic compounds : H2CO, HCN and NH3 in aqueous solution. These studies show that the ratio between the concentrations of the two products CH2(NH2)CN and CH2(OH)CN (precursors of glycine and o~-hydroxyethanoic acid respectively) is proportional to the concentration of free ammonia 1 :Assuming then that in prebiotic conditions the concentration of ammonia was very small (20.10 -6 mol L "l) by comparison to the concentrations of formaldehyde and hydrogencyanide (10 -2 mol L-l), it results that the concentration in ot-aminonitrile was very low compared to that of othydroxynitrile. In a second part, we describe two specific catalytic processes, using formaldehyde or carbonic anhydride as catalysts, which hydrolyse the otaminonitrile either in the ot-aminoacid or in the N-carbamoylaminoacid respectively, shifting by this way the equilibria in favor of these compounds. Assuming that the partial pressure of carbonic anhydride in the prebiotic atmosphere was higher than today (>10 -4 bar), we prove then that the evolution of the prebiotic system H2CO, HCN and NH3 into the Ncarbamoylaminoacid was a "forced" way that nature used as its sole issue to continue its work 2. This result is reinforced by the fact that o~-aminoacids react with potassium isocyanate (a prebiotic reactant) to lead to the same Ncarbamoylaminoacids.