Chemical evolution: the mechanism of the formation of adenine under prebiotic conditions - PubMed (original) (raw)

Chemical evolution: the mechanism of the formation of adenine under prebiotic conditions

Debjani Roy et al. Proc Natl Acad Sci U S A. 2007.

Abstract

Fundamental building blocks of life have been detected extraterrestrially, even in interstellar space, and are known to form nonenzymatically. Thus, the HCN pentamer, adenine (a base present in DNA and RNA), was first isolated in abiogenic experiments from an aqueous solution of ammonia and HCN in 1960. Although many variations of the reaction conditions giving adenine have been reported since then, the mechanistic details remain unexplored. Our predictions are based on extensive computations of sequences of reaction steps along several possible mechanistic routes. H(2)O- or NH(3)-catalyzed pathways are more favorable than uncatalyzed neutral or anionic alternatives, and they may well have been the major source of adenine on primitive earth. Our report provides a more detailed understanding of some of the chemical processes involved in chemical evolution, and a partial answer to the fundamental question of molecular biogenesis. Our investigation should trigger similar explorations of the detailed mechanisms of the abiotic formation of the remaining nucleic acid bases and other biologically relevant molecules.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Proposed steps for the formation of adenine in aqueous ammonium cyanide solution (, –15). Experimentally detected putative intermediates in the abiotic formation of adenine are enclosed in boxes. Two tautomers of AICN can exist; AICN(b) is the more stable. Note that a photoisomerization step is proposed for the formation of AICN from DAMN. DAMN has not been demonstrated to be an adenine intermediate in a nonphotolytic reaction.

Fig. 2.

Thermochemistry of pentamerization of HCN. The relative energies in gas phase are in kilocalories per mole computed at B3LYP/6–311+G**+ZPVE. Entropy is unfavorable but is not included in each step. Overall energy for pentamerization of adenine (5 HCN → C5H5N5) is −93.8 kcal/mol (Δ_G_298 = −53.7 kcal/mol). Note that the last crucial step for formation of pentamer (adenine) from tetramer [AICN(b)] is highly exothermic.

Fig. 3.

Anionic mechanisms are unfeasible in isolation. On optimization, both ii and iii revert back to i (reactants). Free radical and neutral uncatalyzed mechanisms are also not viable because of the very large reaction barriers for the two steps shown.

Fig. 4.

Gas-phase reaction profile [B3LYP/6-31G*] for adenine formation from the less stable AICN(a) isomer, when one explicit H2O molecule is included as catalyst. This pathway is precluded by a second high reaction barrier.

Fig. 5.

Gas-phase potential energy profiles (in kilocalories per mole) for the first key addition step of HCN to AICN(b) (B3LYP/6-311+G** + ZPVE). The uncatalyzed reaction, shown by the dashed line at the top, has a prohibitively high 60.4 kcal/mol barrier. Optimized geometries (in angstroms) are given for reactant complexes (RC), transition structures (TS), and product complexes (PC) having one or two explicit catalytic H2O molecules. Note that these are active participants and reduce the barrier to 38.0 and 37.6 kcal/mol, respectively (entropy was not considered).

Fig. 6.

Reaction profiles for the formation of adenine starting from AICN(b) and HCN in the gas phase and with simulated bulk water solvation by means of explicit solvent-catalyzed mechanisms (two solvent molecules). (a) Reaction profile with water as explicit catalytic molecule (gas phase vs. simulated bulk water solvation). (b) Reaction profile with ammonia as explicit catalytic molecule (gas phase vs. simulated bulk water solvation). The two H2O or NH3 molecules facilitate a “proton relay” by forming an H-bonded “circuit” for the proton transfer in a six-membered transition state. All species shown are stable minima. (Dotted lines depict partial bonds in complexes or transition states.) The comparisons with the gas-phase profiles show the large extent to which simulated water solvation reduces the barrier electrostatically. The first step is rate-determining in all cases. The basis set dependency of the barrier heights is shown by the comparison data at 6-31G* and at 6-311+G** (in parentheses).

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Chemical evolution: the mechanism of the formation of adenine under prebiotic conditions - PubMed (original) (raw)