Reply to Bada and Cleaves: Ab initio free-energy landscape of Miller-like prebiotic reactions

Abstract

In their letter addressing a recent ab initio density-functional theory-based study of Miller-like experiments (1), Bada and Cleaves (2) downplay the role of formamide, citing its half-life, lower than that of HCN, and the fact that the calculations were performed in aqueous phase rather than in gas phase. Miller's original experiment had both gas and condensed phases but ab initio modeling of a full biphasic system was beyond the scope of ref. We are factual about what we observe: Strecker's reactants, within the picosecond timescale of simulations, do not spontaneously react to form larger molecules, except for the appearance of a formimidate ion. On the contrary, a sufficiently intense electric field destabilizes the reactants and induces the barrierless formation of formamide and its evolution either into more complex molecules up to glycine or break up into water and HCN. This is a crucial point, as another criticism of ref. 2 is about the role of formamide in Miller-like reactions.The results found in ref. 1 are strongly supported by further ab initio metadynamics free-energy calculations of formamide decomposition (Fig. 1), carried out following the approach of (3), which indicate that, in both aqueous and gas phases, kinetic barriers and relative free energies of molecular assemblages are similar. The robustness of the calculations is strengthened by the quantitative agreement found with gas phase static quantum chemistry studies (4), which show that, in the absence of an electric field, formamide is more stable than HCN + water by about 10 kcal/mol. Our main result thus remains that the electric field significantly reshapes the freeenergy landscape of the system, modifying the pathway of reactions leading to glycine. We consider this result as most promising in the perspective of novel synthetic routes in prebiotic chemistry.The role of formamide as a key compound in and beyond Miller's historical experiment is confirmed by various groups, including a recent study on shock-induced prebiotic chemistry (5), in which formamide and formic acid are seen as necessary intermediates toward amino acid synthesis, both experimentally and computationally.Finally, Bada and Cleaves claim (2) that mineral surface electric fields are irrelevant in geochemistry. Unfortunately, they do not support their affirmation with any quantitative data, and their claim is not consistent with several studies (6), which show that surface fields, within distances of a few Angstroms from the mineral, have intensities on the order of a few volts per angstrom, i.e., more than necessary for inducing chemical reactions such as the ones reported in ref. 1.

Formamide reaction network in gas phase and solution via a unified theoretical approach: Toward a reconciliation of different prebiotic scenarios

“…., R Nf , whereas z is a measure of the distance from the pathway itself. This class of variables proved crucial to obtain free energy landscapes of a variety of processes including gas-phase chemical reactions with concerted mechanisms (33)(34)(35) and transformations of carbon nanostructures (36). The key ingredient of path collective variables, determining their effectiveness in a given problem, is the definition of distance DðRðtÞ, R k Þ between the atomic configuration at time t and the k th reference structure.…”

A Computational Quantum-Based Perspective on the Molecular Origins of Life’s Building Blocks

“…Although these additional simulations showed that the application of an electric field is capable of decreasing the height of the free-energy barrier, the fact that a significant finite barrier still persists at a strong field intensity of 0.50 V/Å witnesses that the choice of the simple interatomic distance between species forming either C-N or C-C bonds does not represent a good choice for the reproduction of the complex multidimensional free-energy landscape. This way, additional simulations performed by means of metadynamics techniques clarified some of these crucial aspects [ 82 ]. Further DFT-based and metadynamics simulations were executed in direct connection with more recent Miller–Urey-like experiments by Ferus et al [ 20 ].…”

Monitoring the Reactivity of Formamide on Amorphous SiO2 by In-Situ UV-Raman Spectroscopy and DFT Modeling

“…This concept is summarized in Figure 1. This reactions cascade can take place in bulk formamide in significantly boosted in presence of mineral phases in the reaction environment [13][14][15][16][17][18][19][20]. Such catalytic effect does not only affect the nucleobases productivity, but also causes its selective conversion toward specific products depending on the nature of the mineral component.…”