Radical Pathways for the Prebiotic Formation of Pyrimidine Bases from Formamide

Abstract

The prebiotic formation of nucleobases, the building blocks of RNA/DNA, is of current interest. Highly reactive radical species present in the atmosphere under irradiation have been suggested to be involved in the prebiotic synthesis of nucleobases from formamide (FM). We studied several free radical reaction pathways for the synthesis of pyrimidine bases (cytosine, uracil, and thymine) from FM under cold conditions. These pathways are theoretically determined using density functional theory (DFT) computations to examine their kinetic and thermodynamic feasibilities. These free radical reaction pathways share some common reaction types such as H-rearrangement, (•)H/(•)OH/(•)NH2 radical loss, and intramolecular radical cyclization. The rate-determining steps in these pathways are characterized with low energy barriers. The energy barriers of the ring formation steps are in the range of 3-7 kcal/mol. Although DFT methods are known to significantly underestimate the barriers for addition of (•)H radical to neutral species, many of these reactions are highly exergonic with energy release of -15 to -52 kcal/mol and are thus favorable. Among the suggested pathways for formation of cytosine (main route, routes 7a and 1a), uracil (main route, routes 7b and 1b), and thymine (main route and route 26a), the main routes are in general thermodynamically more exergonic and more kinetically favored than other alternative routes with lower overall energy barriers. The reaction energies released following formation of cytosine, uracil, and thymine from FM via the main radical routes amount to -59, -81, and -104 kcal/mol, respectively. Increasing temperature induces unfavorable changes in both kinetic and thermodynamic aspects of the suggested routes. However, the main routes are still more favored than the alternative pathways at the temperature up to the boiling point of FM.

Cyanoacetaldehyde as a building block for prebiotic formation of pyrimidines

“…In contrast to the cyanoacetaldehyde based pathways proposed in the present work, previous studies have suggested competing radical based pathways using precursors such as acetylene and urea, formamide and HCN or acetylene, and 1,2‐diaminomaleonitrile . The highest barriers for the cytosine formation reported in these studies at the same theoretical level lie in the range of 24 to 40 kcal mol −1 , which is greater than the highest barrier of 16 kcal mol −1 observed in our study.…”

“…The selection of •NH 2 /NH 3 assisted pathways over other competing pathways reiterates the importance of •NH 2 /NH 3 pair in making prebiotic routes to formation of pyrimidines feasible by providing lower barriers. This, in turn, signposts the catalytic role of the •NH 2 /NH 3 pair, which has been previously highlighted in the formamide based mechanism for pyrimidines formation …”

“…Geometry optimizations and zero‐point vibrational energy corrected electronic energies of reactants, transition states, intermediates, and products along the reaction pathways were obtained in the gas phase at B3LYP/6–311G(d,p). This method has been used in analogy with previous studies on radical based pathways of prebiotically important reactions . The stationery points on the reaction pathways were characterized as minima (reactants, intermediates, and products) and saddle points (transition states) using vibrational frequency calculations.…”

“…Additionally, a Mg 2+ catalyzed mechanistic pathway for the formation of 2‐pyrimidinone based nucleoside has been explored by Sheng et al However, the high influx of ultraviolet (UV) radiations on primitive earth, coupled with the relevance of radicals to spark discharge experiments, laser‐driven plasma impact simulations, and the presence of cosmic, γ, and UV radiations on the present‐day Titan's atmosphere, suggest that reactions for the formation of nucleobases are likely to follow radical based mechanisms. On these lines, Jeilani et al suggested a free radical route for the formation of triazines and pyrimidines from urea in a water‐ice mixture, and further formulated free radical based mechanisms for the formation of these pyrimidines from 1,2‐diaminomaleonitrile and formamide, acetylene and urea, as well as formamide and HCN or acetylene . Similarly, Ferus et al theoretically explored a radical induced, formamide based synthesis of nucleobases in a high energy impact scenario …”

Multimodal Vacuum-Assisted Plasma Ion (VaPI) Source with Transmission Mode and Laser Ablation Sampling Capabilities

“…LA-VaPI was used to monitor natural and alternative nucleobase products formed in formamide and pyrazine model prebiotic reactions. The synthetic pathways postulated for the formamide reaction have been reviewed in the literature [48,50,51], and the reaction pathway for the predicted pyrazine products is outlined by Scheme 1 in supporting information. Basic sample preparation involved collecting portions of the crude product or fractions of the desalted mixture (see the Experimental section for details), followed by resuspension in DI water and filtration to remove large particulates prior to laser ablation from the sample ampoule.…”