Next Article in Journal
A Quasigroup Approach for Conservation Laws in Asymptotically Flat Spacetimes
Previous Article in Journal
The Iwasawa–Taniguchi Effect in Compton-thick Seyfert 2 Galaxies with Extended Hard X-Ray Emission
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Universe
Volume 11
Issue 10
10.3390/universe11100349
universe-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Thermodynamic Assessment of Prebiotic Molecule Formation Pathways on Comets

by
Luca Tonietti
1,2
1
Department of Science and Technology, Parthenope University of Naples, 80143 Naples, Italy
2
INAF-OAC, Osservatorio Astronomico di Capodimonte, 80131 Naples, Italy
Universe 2025, 11(10), 349; https://doi.org/10.3390/universe11100349
Submission received: 28 May 2025 / Revised: 26 September 2025 / Accepted: 15 October 2025 / Published: 18 October 2025
(This article belongs to the Section Planetary Sciences)
Browse Figures
Versions Notes

Abstract

Comets are chemically rich and thermally extreme, spanning surface temperatures from ~50 K in the Oort Cloud to >1000 K for sungrazing bodies. These conditions may support key steps of prebiotic chemistry, including the synthesis of nucleic acid precursors. This study present a thermodynamic evaluation of seven candidate reactions, producing nitrogenous bases, sugars, nucleosides, and nucleotides, across the cometary temperature spectrum, 50–1000 K. Purine nucleobase synthesis, including adenine formation via aminoacetonitrile polymerization and HCN polymerization, is strongly exergonic at all temperatures. Sugar formation from formaldehyde is also exergonic, while intermediate pathways, e.g., 2-aminooxazole synthesis, become thermodynamically viable only above ~700 K. Nucleoside formation is thermodynamically neutral at low T but becomes favorable at elevated temperatures, whereas phosphorylation to AMP, i.e., adenosine-monophosphate, a nucleotide serving as a critical regulator of cellular energy status, remains highly endergonic under the entire T range studied. My analysis suggests that, under standard-state assumptions, comets can thermodynamically support formation routes of nitrogenous bases and simple sugars but not a complete nucleotide assembly. This supports a dual-phase origin scenario, where comets act as molecular reservoirs, with further polymerization and biological activation occurring post-delivery on planetary surfaces. Importantly, these findings represent purely thermodynamic assessments under standard-state assumptions and do not address kinetic barriers, catalytic influences, or adsorption effects on ice or mineral surfaces. The results should therefore be viewed as a baseline map of feasibility, subject to modifications in more complex chemical environments.

1. Introduction

Comets are “Cosmic Shuttles” known to harbor organic molecules relevant to prebiotic chemistry, including hydrogen cyanide (HCN) [1], ammonia (NH3) [2], formaldehyde (H2CO) [3], methanol (CH3OH) [4], formic acid (HCOOH) [5], and phosphate-bearing minerals [6], as confirmed by direct and indirect observational data from space missions such as Rosetta, e.g., ROSINA (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis), ALMA (Atacama Large Millimeter/Submillimeter Array), and COSAC (gas analyzer Cometary Sampling and Composition) to comet 67P/Churyumov-Gerasimenko [7]. The detection of these molecular precursors, also in dust [8], is of crucial importance: they represent essential building blocks for the synthesis of complex organic molecules such as amino acids, sugars, nucleobases, nucleosides, and nucleotides, i.e., main components required for the emergence of life [9]. Cometary nuclei likely are over most of their history at temperatures of about 50 K while their surfaces and the outer layers, where most chemistry is active, are subject to extreme thermal cycling ranging from cryogenic temperatures of ~50 K in the Oort cloud to over 300 K at ~1 AU and even above 1000 K for sungrazing comets [10]. In addition, cometary surfaces are exposed to ultraviolet (UV) radiation, cosmic ray, and sporadic heating during perihelion passages [11]. These distinctive conditions enable chemical reactions that might be energetically unfavorable or kinetically inaccessible under standard terrestrial conditions, making comets ideal natural laboratories for prebiotic chemistry [12]. Within nuclei superficial regions, photochemical activation and radical-mediated pathways can facilitate reaction routes not typically available under ambient planetary conditions [13].
Several synthetic pathways for nucleobases and sugars formation under such conditions have been proposed. These include the Strecker synthesis, radical polymerization of formamide (HCONH2), and HCN-based oligomerization [14,15]. Compounds such as glycolaldehyde (HOCH2-CHO) and formamide have been detected in cometary comae [16] supporting the astrochemical plausibility of these pathways. The presence of minerals in cometary nuclei [17], including silicates [18], metal oxides, sulfides [19], and phosphates, can provide catalytic sites that can influence chemical reactivity and selectivity. The role of comets in delivering prebiotic molecules to Earth, a key aspect of the pseudo-panspermia hypothesis, has gained increasing attention [20]. Laboratory experiments simulating cometary impact conditions demonstrate the survival of complex organics encapsulated within icy or mineral matrices during atmospheric entry [21]. A systematic understanding of the thermodynamic feasibility of these synthetic reactions under cometary conditions is still to be investigated.
In this study, a quantitative thermodynamic analysis is performed to evaluate whether reactions involved in the prebiotic synthesis of nucleobases, sugars, nucleosides, and nucleotides are thermodynamically viable on cometary surfaces. Calculations are based on standard-state Gibbs free energy changes, assuming solid-phase chemistry and excluding other intermediates unless explicitly supported by environmental justification. This approach aims to define the thermodynamic constraints governing organic reactions in cometary environments, some of which may be critical to prebiotic chemical evolution. It is important to note that the present work focuses exclusively on thermodynamic feasibility, neglecting kinetic barriers and catalytic effects that may operate on cometary surfaces. While this simplification allows for a systematic mapping of Gibbs free energy changes, it represents only part of the full prebiotic picture. The analysis directly connects to the broader question of life’s origins, since the cometary molecules evaluated here, bases, sugars, and simple nucleosides, are key precursors of ribonucleotides and thus of RNA itself.

2. Thermodynamic Calculations

To evaluate the thermodynamic feasibility for seven key prebiotic reactions, involved in prebiotic synthesis of nucleobases, sugars, nucleosides, and nucleotides, to occur on cometary nuclei, I estimated the Gibbs free energy variation, ΔG, at temperature, T, spanning from 50 K to 1000 K, mimicking different cometary conditions. Standard enthalpies of formation (ΔH°f) and molar entropies (S°) for the molecular species involved were collected from experimental databases, e.g., NIST (www.nist.gov/publications, accessed on 20 April 2025), Cheméo (www.chemeo.com, accessed on 20 April 2025), and from [22] for adenosine and adenosine 5′-monophosphate. Where unavailable, values were estimated by analogy with structurally related molecules. All molecular states were considered in their condensed form, i.e., solid or liquid, except for CO which was treated as gas under standard conditions. This approximation is consistent with thermodynamic convention for condensed-phase systems, where activities of solids and liquids are typically set to unity.
The following thermodynamic equation was applied:
ΔG = ΔH − TΔS
where ΔH and ΔS for each reaction were calculated from the sum of the products minus the sum of the reactants. In cases where only gas-phase values were available, e.g., cyanamide, aminoacetonitrile, the solid-state enthalpy of formation was calculated by subtracting the enthalpy of sublimation (ΔH_sub) from the gas-phase value:
ΔH°f (solid) = ΔH°f (gas) − ΔH_sub
Standard molar entropies were assumed to vary minimally. For AMP aqueous-phase values [22] were used as an approximation for solid-state properties. All calculations and assumptions are summarized in Table 1 and Table 2. These calculations rely on standard-state assumptions, with activities of condensed species set to unity. While actual ΔG values depend on specific concentrations through ΔG = ΔG0 + RT ln Q, such data are not available for cometary interiors. The approach focuses on identifying relative thermodynamic trends across a range of temperatures, rather than predicting reaction yields. Reactions with ΔG > 0 are considered thermodynamically unfeasible, reactions with ΔG < 0 are considered thermodynamically feasible, and reactions with ΔG ≈ 0 are considered thermodynamically neutral.

3. Results

3.1. Formation of Nitrogenous Bases via Strecker Synthesis

In the Strecker Synthesis, hydrogen cyanide (HCN), ammonia (NH3), and formaldehyde (H2CO) react to form aminoacetonitrile (NH2CH2CN), a relatively stable intermediate under cometary cryogenic conditions:
HCN + NH3 + H2CO → NH2CH2CN + 1/2O2 + H2
Under moderate UV irradiation, aminoacetonitrile can polymerize and subsequent cyclize to adenine (C5H5N5):
5NH2CH2CN + 5CO2 + hν → C5H5N5 + 5NH3 + 5CO + 5/2O2
I computed the ΔG for reaction (R2) at temperatures from 50 to 1000 K (Table 2). My results confirm that this reaction is strongly exergonic across all surface-relevant temperatures, with ΔG decreasing from −402.5 kcal mol−1 at 50 K to −450.0 kcal mol−1 at 1000 K. At 200 K the calculated ΔG is −410.0 kcal mol−1, driven almost entirely by the enthalpic gain associated with aromatic ring formation in adenine. The entropy term (TΔS) is minimal at low temperatures, reinforcing the enthalpy-dominant profile of the reaction. This makes the Strecker-based synthesis of adenine the most thermodynamically favorable pathway among all routes analyzed in this study. Even in deep-space cometary reservoirs (~50 K), the reaction remains spontaneous and exergonic.
It is important to emphasize that these findings are purely thermodynamic and do not address kinetic factors. Although UV photons could initiate polymerization and radical formation, kinetic barriers associated with cyclization are not considered here. An important limitation involves the potential transformation of aminoacetonitrile under transient aqueous conditions. Aminoacetonitrile can hydrolyze to glycine (NH2CH2COOH), a compound that has been detected in cometary samples [23,24,25,26]. While this competing reaction could reduce yields of adenine such kinetic considerations and environmental perturbations fall outside the scope of this purely thermodynamic evaluation.

3.2. Formation of Nitrogenous Bases via Radical Synthesis from Formamide

Formamide (HCONH2), spectroscopically detected in cometary nuclei, can be an alternative precursor for nitrogenous base [27] formation through radical-driven reactions induced by UV radiation and cosmic rays:
5HCONH2 + hν → C5H5N5 + 5H2 + 5/2O2
At T = 200 K, ΔG is −32.0 kcal mol−1, indicating that the reaction is moderately exergonic. The exothermicity can derive from the formation of aromatic rings in adenine [28]. As temperature increases, the entropy contribution becomes more favorable, and ΔG becomes increasingly negative, reaching −60.0 kcal mol−1 for T = 1000 K (Table 2). These results suggest that this pathway is thermodynamically viable over the entire surface temperature range of cometary bodies, although less favorable than the Strecker pathway (reaction 2). Under cometary UV exposure, formamide is prone to fragmentation into simpler species such as NH3, CO2, or HCN, potentially competing with nucleobase formation [29].

3.3. Orò-Type Polymerization

HCN, i.e., one of the most abundant organic molecules detected in astrophysical environments and potentially involved in prebiotic chemistry, is known to undergo spontaneous polymerization under cryogenic conditions, forming a macromolecular material referred to as HCN polymer or polyamino-cyanomethylene [30]. This solid-state polymer is stable due to a combination of two factors: (i) extensive hydrogen bonding, conjugated structure, and (ii) entrapment within water ice matrices, which reduce molecular mobility and degradation in cold environments. The breakdown of this polymer can produce adenine and potentially other purine derivatives, according to the following overall reactions:
5HCN + Δ + hν → (C5H5N5)polymer
If we consider the polymer as 6HCN:
6HCN + H2 + O2 + Δ + hν → C5H5N5 + NH3 + CO2
These reactions have attracted significant interest as a possible reservoir mechanism, as they could store biologically relevant molecules, releasing them only upon conditions that allow depolymerization.
At 200 K the ΔG is approximately −98 kcal mol−1 and the reaction becomes even more favorable at higher temperatures, reaching values near −130 kcal mol−1 at 1000 K. This derives both from the aromatic stabilization of adenine and from the increased entropy associated with the release of volatile by-products such as NH3, and CO2 during breakdown. Although HCN polymers may kinetically require activation energy or aqueous conditions for nucleobase release [31], such kinetic considerations and related activation mechanisms are not considered here. Thus, cometary environments are thermodynamically ideal for the preservation and accumulation of HCN polymers, but the potential transition to prebiotic purines upon planetary delivery is possibly ruled by kinetic factors in addition to thermodynamics.

3.4. Cyanamide-Based Reactions

Cyanamide (NH2CN), another plausible cometary molecule, reacts with glycolaldehyde (HOCH2CHO) to form intermediates leading to nucleobases:
NH2CN + HOCH2CHO → C3H4N2O + H2 + 1/2O2
The structural stability of 2-aminooxazole, attributed to its ring closure and intramolecular hydrogen bonding, is significant under cryogenic conditions, where reduced molecular motion enhances the persistence of such intermediates. This makes it a promising candidate for long-lived cometary reservoirs of nucleotide precursors. Thermodynamic calculations show that this reaction is endergonic under cometary-relevant temperatures. At 200 K the ΔG is approximately +16 kcal mol−1, indicating that the reaction is not spontaneous under typical surface conditions of cometary bodies. Even at the lowest evaluated temperature (50 K) the ΔG remains positive, and only at elevated temperatures approaching 1000 K does the reaction become thermodynamically favorable (Table 2). The formation of 2-aminooxazole is thermodynamically unfeasible across most of the full cometary temperature range considered here.

3.5. Formation of Pentose Sugars and Nucleosides/Nucleotides

Two primary pathways have been proposed for pentose sugar formation under prebiotic conditions. The first is the classical Formose reaction, where formaldehyde (H2CO) undergoes autocatalytic polymerization to ribose:
5H2CO → C5H10O5 (ribose)
An alternative pathway involves Glycolaldehyde Polymerization, utilizing glycolaldehyde (HOCH2CHO):
HOCH2CHO + 3H2CO → C5H10O5
Thermodynamic analysis confirms that the formation of ribose from formaldehyde is exergonic, with ΔG, calculated at 200 K, is approximately −76 kcal mol−1 and even more favorable at higher temperatures.
Compared to the classical Formose reaction pathway, the alternative ribose synthesis route shown in Equation (10) is slightly more exergonic. At 298 K, the ΔG for this alternative pathway is approximately −49.2 kJ/mol, while the Formose pathway yields a net ΔG of approximately −45.1 kJ/mol. Although the difference is modest, it suggests that the alternative route may be thermodynamically more favorable under standard conditions. Formaldehyde and glycolaldehyde are chemically versatile to undergo alternative reactions, including the Cannizzaro reaction, where two H2CO molecules yield formic acid (HCOOH) and methanol (CH3OH). From a thermodynamic standpoint, the Cannizzaro reaction is strongly exergonic (ΔG ≈ −55.4 kJ/mol at 298 K) and thus represents a competitive pathway for formaldehyde consumption. However, it does not lead to sugar formation and may act as a thermodynamic sink, diverting carbon away from more complex prebiotic molecules. Moreover, the Formose reaction lacks selectivity and tends to produce complex mixtures of sugars and polyhydroxy oligomers, with little control over chain length or stereochemistry [32]. While low temperatures may slow degradation, thermodynamic feasibility alone does not guarantee ribose stability or accumulation.
The subsequent synthesis of nucleosides proceeds through condensation reactions, e.g.,
C5H5N5 (Adenine) + C5H10O5 (Ribose) → C10H13N5O4 (Adenosine) + H2O
Thermodynamic calculations show that reaction (R9) is mildly endergonic across cometary-relevant temperatures. At 200 K, ΔG is approximately +3.0 kcal mol−1, decreasing slightly at higher temperatures, e.g., +2.0 kcal mol−1 at 300 K, and becoming marginally exergonic only above ~600–800 K (−1.0 to −3.0 kcal mol−1). These values indicate that the reaction is thermodynamically neutral under standard cometary conditions. While actual directionality may depend on concentration gradients (ΔG = ΔG0 + RT ln Q), such data are not available for cometary interiors. Therefore, only standard-state behavior is evaluated here.
Subsequent phosphorylation, assisted by UV-activated phosphate minerals, can lead to nucleotide formation:
C10H13N5O4 (Adenosine) + H3PO4 → C10H14N5O7P (Adenosine monophosphate (AMP)) + H2O
Reaction (R10), in contrast, is strongly endergonic under all cometary-like conditions. At 200 K the reaction has a ΔG of approximately +66.0 kcal mol−1 and remains energetically unfavorable even at 1000 K (ΔG ≈ +50.0 kcal mol−1). These values indicate that AMP formation is thermodynamically unfeasible across the full cometary temperature range.

4. Discussion

This study provides a thermodynamic evaluation of key reactions leading to nitrogenous bases, sugars, nucleosides, and nucleotides across a wide temperature range (50–1000 K) (Figure 1).
The results reveal systematic trends that differentiate which types of molecular synthesis are thermodynamically feasible under cometary temperatures and which are thermodynamically prohibited, regardless of environmental complexity The surface temperature of comets spans orders of magnitude depending on their orbital history and family. Long-period comets originating from the Oort Cloud spend most of their lifetime at cryogenic temperatures (~50 K), interrupted by brief warming during solar approaches [33,34]. Jupiter Family Comets (JFCs) typically oscillate between 4–6 AU and 1 AU, experiencing intermediate thermal cycling (100–250 K) [33]. In contrast, sungrazing comets, such as those in the Kreutz group, can reach surface temperatures exceeding 800–1000 K during perihelion [12] (Figure 2). Assessing thermodynamic feasibility across this spectrum provides a map of chemical potential within cometary systems.
The formation of aromatic nucleobases from simple precursors is consistently thermodynamically favorable across all temperature regimes. The Strecker-type polymerization of aminoacetonitrile to adenine is strongly exergonic (ΔG from −402 kcal mol−1 at 50 K to −450 kcal mol−1 at 1000 K), indicating potential synthesis under even the Oort Cloud conditions. Hydrolysis of HCN polymers to adenine is also highly favorable (ΔG ≈ −92 to −130 kcal mol−1), with growing exergonicity at higher temperatures due to growing entropy contributions. This supports the potential for nucleobase accumulation under both cold and warm cometary conditions, driven by different dominant processes. The formamide-derived pathway to adenine is moderately exergonic, transitioning from ΔG ≈ −27 kcal mol−1 at 50 K to ≈−60 kcal mol−1 at 1000 K. While viable at all temperatures, its favorability is lower compared to HCN-based pathways. Some pathways shift from endergonic to exergonic ΔG values as temperature rises, suggesting conditional thermodynamic feasibility. For instance, 2-aminooxazole synthesis from cyanamide and glycolaldehyde is endergonic below ~600–700 K (ΔG ≈ +23 kcal mol−1 at 50 K, +16 kcal mol−1 at 200 K) but becomes exergonic above ~800 K. This implies that such pyrimidine precursors cannot form under cold cometary conditions and require elevated temperatures for thermodynamic favorability.
The Formose reaction is exergonic across all temperatures considered, i.e., ΔG from −71.5 kcal mol−1 at 50 K to −100 kcal mol−1 at 1000 K. Side reactions, e.g., Cannizzaro disproportionation, and the low selectivity of sugar formation reduce the chance of ribose accumulation. Ribose is also chemically fragile, prone to racemization and decomposition under warming. Although cold trapping may preserve it at low temperatures, its persistence at biologically relevant fidelity is questionable.
The reaction of adenine and ribose to form adenosine lies thermodynamically near neutral with ΔG ranging from +4.5 kcal mol−1 at 50 K to ≈−5 kcal mol−1 at 1000 K. This suggests marginal thermodynamic favorability only at high temperatures, and infeasibility in cold regions. No spontaneous condensation is expected under cryogenic conditions. The phosphorylation of adenosine to AMP is thermodynamically prohibited at all temperatures (ΔG from +69 kcal mol−1 at 50 K to +50 kcal mol−1 at 1000 K). No known cometary thermal environment can make this step favorable under standard-state thermodynamics.
This analysis confirms that cometary environments cannot spontaneously support full nucleotide synthesis. However, early steps such as nitrogenous base and simple sugar formation are thermodynamically feasible, especially under cold conditions that stabilize intermediates and suppress side reactions. Upon planetary delivery, cometary materials encounter new environmental regimes: (i) higher temperatures (273–373 K), (ii) atmospheric pressure (~1 bar), (iii) metal-rich surfaces, which may enable kinetically slow or thermodynamically hindered reactions. While this study does not explore these mechanisms, the thermodynamic groundwork established here could provide a baseline to assess the plausibility of such transformations.
A further limitation of this work is the assumption of isolated, bare molecules. In reality, cometary surfaces host complex mixtures and abundant solid phases, e.g., silicates, metal oxides, phosphates, ices, which can alter both thermodynamic states and kinetic accessibility. Adsorption of organics onto ice matrices or mineral surfaces can change Gibbs free energy by stabilizing intermediates, lowering enthalpic costs, or altering entropy contributions. Laboratory simulations have shown that catalytic minerals such as montmorillonite clays or phosphate-rich phases can promote condensation reactions otherwise unfavorable in the bulk phase. Similarly, hydrogen-bonded networks in water–ice mixtures can provide stabilization that is not captured by standard-state values. As a concrete example, the adenine-ribose condensation step (reaction R9) has a calculated ΔG of +3.0 kcal mol−1 at 200 K under standard-state assumptions (Table 2), i.e., slightly endergonic. Adsorption enthalpies reported for adenine on montmorillonite or silica surfaces are in the range of –10 to –20 kcal mol−1 [27]. If a conservative stabilization of –15 kcal mol−1 is considered, the effective free energy change becomes ΔG_eff ≈ –12 kcal mol−1, rendering the condensation exergonic. This should not be interpreted as catalysis in the kinetic sense, which lowers activation barriers without altering thermodynamic balances, but rather as a shift in the thermodynamic reference state: the reaction no longer proceeds from isolated adenine and ribose but from adsorbed species with different enthalpic baselines. Such stabilization illustrates how surface-bound molecules can qualitatively change the thermodynamic feasibility of key steps, even if kinetic accessibility remains an independent limitation.
These results also carry implications for the RNA world hypothesis. The cometary synthesis of adenine, ribose, and other simple sugars represents not only general organic molecules but a supply of precise precursors required for ribonucleotide assembly. Although nucleotide formation itself is thermodynamically prohibited in cometary settings, delivery of such precursors to the early Earth could have provided essential inputs for ribonucleotide synthesis under terrestrial conditions. In particular, comet-derived purines, ribose, and HCN polymers may have contributed to the abiotic formation of ribonucleotides, thereby feeding into the emergence of RNA as the first informational and catalytic biopolymer. Beyond its role as an informational polymer, RNA has also been proposed as a metabolic scaffold in early evolution, where ribozymes could have catalyzed primitive reactions linking energy transduction to molecular complexity [35,36]. This perspective reinforces the significance of cometary delivery of ribonucleotide precursors, as it could have supported both genetic and metabolic innovation at life’s origin.

5. Conclusions

I performed a quantitative thermodynamic analysis of seven key reactions involved in prebiotic synthesis of nucleobases, sugars, nucleosides, and nucleotides. For each pathway, I computed the Gibbs free energy change (ΔG) over a wide temperature range (50–1000 K), chosen to reflect the diverse thermal regimes observed across different cometary families: from cryogenic preservation in the Oort Cloud to intense solar heating in sungrazers and perihelion-active Jupiter Family Comets. By systematically mapping ΔG across this spectrum, I capture both cold-trapping potential and temperature-driven reactivity, offering a unified framework for understanding cometary chemistry across evolutionary timescales. The results reveal a strong temperature dependence across pathways and clear thermodynamic hierarchy. Several nucleobase-forming reactions are highly exergonic even at cryogenic temperatures, e.g., −400 kcal mol−1 at 200 K, while nucleotide assembly remains thermodynamically prohibited up to 1000 K. These trends help to delineate which molecular classes can thermodynamically form and accumulate on comets, and which require non-cometary environments. By integrating cometary temperatures regimes, this study defines the thermodynamic boundaries of cometary prebiotic and organic chemistry and supports the evaluation of exogenous molecular delivery during early chemical evolution. Aromatic nucleobase synthesis, e.g., adenine from aminoacetonitrile, formamide, or HCN polymers, is thermodynamically favorable at all evaluated temperatures. These reactions are spontaneous even at 50 K, supporting the idea that cometary environments can enable the synthesis and long-term preservation of nitrogenous bases without requiring solar heating or kinetic forcing. Sugar synthesis via the Formose reaction is also thermodynamically favorable, though selectivity limitations and competition with exergonic side reactions such as Cannizzaro disproportionation may reduce net yields of ribose. Ribose stability remains temperature-sensitive, with degradation above ~250 K unless buffered by mineral matrices or ice encapsulation. Other reactions, such as 2-aminooxazole formation from cyanamide and glycolaldehyde, show ΔG > 0 at low temperatures and become exergonic only above 700 K, reflecting a temperature-induced shift in thermodynamic. These reactions are prohibited in cryogenic environments but feasible at higher temperatures, such as during perihelion passages or planetary impact heating.
Nucleoside formation is thermodynamic neutral at low T (from 50 to 400 K), and becomes exergonic at high temperatures, especially >700 K. This suggests limited feasibility under cold conditions and possible progression only under higher-temperature regimes. In contrast, phosphorylation to form nucleotides, e.g., AMP, thermodynamically unfeasible across the entire cometary temperature range, with ΔG consistently above +50 kcal mol−1.
Overall, cometary environments are thermodynamically favorable for the synthesis and preservation of nitrogenous bases and simple sugars, especially under low-temperature conditions. Full nucleotide assembly exceeds the thermodynamic limits of cometary settings, supporting a two-phase model of chemical evolution: (i) comets as low-temperature synthesis and storage environments for key intermediates and (ii) planetary surfaces as settings for thermodynamically demanding processes leading to functional biopolymers. In particular, the results reinforce the idea that cometary delivery may have supplied purines, ribose, and HCN-derived polymers that later converged toward RNA synthesis under terrestrial conditions. This provides a thermodynamic underpinning for the RNA world hypothesis, in which comet-delivered precursors fed into the first genetic and catalytic biopolymer. At the same time, our framework should be regarded as a baseline, since it neglects kinetic barriers, catalytic influences, and adsorption effects, all of which may further modulate feasibility in realistic cometary environments. Thus, while kinetic barriers and environmental complexities remain to be addressed, the present thermodynamic framework delineates which cometary reactions are feasible in principle, thereby identifying the most plausible pathways through which exogenous delivery could have contributed to the emergence of RNA-centered biochemistry on the early Earth.

Funding

This work was conducted thanks to the following funding: the ASI-INAF agreements I/024/12/0 and 2020-4-HH.0, from the Italian Space Agency (ASI).

Data Availability Statement

Data is contained within the article.

Acknowledgments

The author would like to thank the Astrobiology and Cosmic Physics Laboratory (ACPL) at the Parthenope University of Naples for their support in conducting this research, as well as the Istituto Nazionale di Astrofisica (INAF). The author is especially grateful to Nadia Balucani for her invaluable support throughout the study.

Conflicts of Interest

The author declares no conflicts of interest.

References

  1. Bergman, P.; Lerner, M.S.; Olofsson, A.O.H.; Wirström, E.; Black, J.H.; Bjerkeli, P.; Parra, R.; Torstensson, K. Emission from HCN and CH3OH in Comets—Onsala 20-m Observations and Radiative Transfer Modelling. Astron. Astrophys. 2022, 660, A118. [Google Scholar] [CrossRef]
  2. Biver, N.; Crovisier, J.; Bockelée-Morvan, D.; Szutowicz, S.; Lis, D.C.; Hartogh, P.; Val-Borro, M.d.; Moreno, R.; Boissier, J.; Kidger, M.; et al. Ammonia and Other Parent Molecules in Comet 10P/Tempel 2 from Herschel/HIFI and Ground-Based Radio Observations. Astron. Astrophys. 2012, 539, A68. [Google Scholar] [CrossRef]
  3. Vanysek, V.; Wickramasinghe, N.C. Formaldehyde Polymers in Comets. In Astronomical Origins of Life: Steps Towards Panspermia; Hoyle, F., Wickramasinghe, N.C., Eds.; Springer: Dordrecht, The Netherlands, 2000; pp. 115–124. [Google Scholar] [CrossRef]
  4. Drozdovskaya, M.N.; Schroeder, I.I.R.H.G.; Rubin, M.; Altwegg, K.; van Dishoeck, E.F.; Kulterer, B.M.; De Keyser, J.; Fuselier, S.A.; Combi, M. Prestellar Grain-Surface Origins of Deuterated Methanol in Comet 67P/Churyumov–Gerasimenko. Mon. Not. R. Astron. Soc. 2021, 500, 4901–4920. [Google Scholar] [CrossRef]
  5. Biver, N.; Bockelée-Morvan, D.; Debout, V.; Crovisier, J.; Boissier, J.; Lis, D.C.; Russo, N.D.; Moreno, R.; Colom, P.; Paubert, G.; et al. Complex Organic Molecules in Comets C/2012 F6 (Lemmon) and C/2013 R1 (Lovejoy): Detection of Ethylene Glycol and Formamide. Astron. Astrophys. 2014, 566, L5. [Google Scholar] [CrossRef]
  6. Rivilla, V.M.; Drozdovskaya, M.N.; Altwegg, K.; Caselli, P.; Beltrán, M.T.; Fontani, F.; van der Tak, F.F.S.; Cesaroni, R.; Vasyunin, A.; Rubin, M.; et al. ALMA and ROSINA Detections of Phosphorus-Bearing Molecules: The Interstellar Thread between Star-Forming Regions and Comets. Mon. Not. R. Astron. Soc. 2020, 492, 1180–1198. [Google Scholar] [CrossRef]
  7. Goesmann, F.; Rosenbauer, H.; Bredehöft, J.H.; Cabane, M.; Ehrenfreund, P.; Gautier, T.; Giri, C.; Krüger, H.; Le Roy, L.; MacDermott, A.J.; et al. Organic Compounds on Comet 67P/Churyumov-Gerasimenko Revealed by COSAC Mass Spectrometry. Science 2015, 349, aab0689. [Google Scholar] [CrossRef]
  8. Della Corte, V.; Ferretti, S.; Piccirillo, A.M.; Zakharov, V.; Di Paolo, F.; Rotundi, A.; Ammannito, E.; Amoroso, M.; Bertini, I.; Di Donato, P.; et al. DISC—The Dust Impact Sensor and Counter on-Board Comet Interceptor: Characterization of the Dust Coma of a Dynamically New Comet. Adv. Space Res. 2023, 71, 3457–3467. [Google Scholar] [CrossRef]
  9. Yadav, M.; Pulletikurti, S.; Yerabolu, J.R.; Krishnamurthy, R. Cyanide as a Primordial Reductant Enables a Protometabolic Reductive Glyoxylate Pathway. Nat. Chem. 2022, 14, 170–178. [Google Scholar] [CrossRef]
  10. Jewitt, D.; Luu, J.; Li, J. Demise of Kreutz Sungrazing Comet C/2024 S1 (ATLAS). Astron. J. 2025, 169, 105. [Google Scholar] [CrossRef]
  11. Belousov, D.V.; Pavlov, A.K. Cometary Outbursts in the Oort Cloud. Icarus 2024, 415, 116066. [Google Scholar] [CrossRef]
  12. Huebner, W.F.; Boice, D.C. Comets as a Possible Source of Prebiotic Molecules. Orig. Life Evol. Biosph. 1991, 21, 299–315. [Google Scholar] [CrossRef]
  13. Rotavera, B.; Taatjes, C.A. Influence of Functional Groups on Low-Temperature Combustion Chemistry of Biofuels. Prog. Energy Combust. Sci. 2021, 86, 100925. [Google Scholar] [CrossRef]
  14. Bera, P.P.; Stein, T.; Head-Gordon, M.; Lee, T.J. Mechanisms of the Formation of Adenine, Guanine, and Their Analogs in UV-Irradiated Mixed NH3:H2O Molecular Ices Containing Purine. Astrobiology 2017, 17, 771–785. [Google Scholar] [CrossRef]
  15. Singh, S.K.; Zhu, C.; La Jeunesse, J.; Fortenberry, R.C.; Kaiser, R.I. Experimental Identification of Aminomethanol (NH2CH2OH)—The Key Intermediate in the Strecker Synthesis. Nat. Commun. 2022, 13, 375. [Google Scholar] [CrossRef]
  16. Biver, N.; Bockelée-Morvan, D.; Moreno, R.; Crovisier, J.; Colom, P.; Lis, D.C.; Sandqvist, A.; Boissier, J.; Despois, D.; Milam, S.N. Ethyl Alcohol and Sugar in Comet C/2014 Q2 (Lovejoy). Sci. Adv. 2015, 1, e1500863. [Google Scholar] [CrossRef]
  17. Rotundi, A.; Rietmeijer, F.J.M.; Ferrari, M.; Della Corte, V.; Baratta, G.A.; Brunetto, R.; Dartois, E.; Djouadi, Z.; Merouane, S.; Borg, J.; et al. Two Refractory Wild 2 Terminal Particles from a Carrot-Shaped Track Characterized Combining MIR/FIR/Raman Microspectroscopy and FE-SEM/EDS Analyses. Meteorit. Planet. Sci. 2014, 49, 550–575. [Google Scholar] [CrossRef]
  18. Nuth, J.A.; Johnson, N.M. Crystalline Silicates in Comets: How Did They Form? Icarus 2006, 180, 243–250. [Google Scholar] [CrossRef]
  19. Rietmeijer, F.J.M. Sulfides and Oxides in Comets. Astrophys. J. Part 2—Lett. 1988, 331, L137–L138. [Google Scholar] [CrossRef]
  20. McKay, C.P.; Davies, P.C.W.; Worden, S.P. Directed Panspermia Using Interstellar Comets. Astrobiology 2022, 22, 1443–1451. [Google Scholar] [CrossRef] [PubMed]
  21. Bernstein, M.P.; Allamandola, L.J.; Sandford, S.A. Complex Organics in Laboratory Simulations of Interstellar/Cometary Ices. Adv. Space Res. 1997, 19, 991–998. [Google Scholar] [CrossRef]
  22. Boerio-Goates, J.; Francis, M.R.; Goldberg, R.N.; da Silva, M.A.; da Silva, M.D.; Tewari, Y.B. Thermochemistry of Adenosine. J. Chem. Thermodyn. 2001, 33, 929–947. [Google Scholar] [CrossRef]
  23. Galimova, G.R.; Medvedkov, I.A.; Mebel, A.M. The Role of Methylaryl Radicals in the Growth of Polycyclic Aromatic Hydrocarbons: The Formation of Five-Membered Rings. J. Phys. Chem. A 2022, 126, 1233–1244. [Google Scholar] [CrossRef]
  24. Alonso, E.; Kolesniková, L.; Bialkowska, E.; Kisiel, Z.; león, I.; Guillemin, J.; Alonso, J. Glycinamide, a Glycine Precursor, Caught in the Gas Phase: A Laser-Ablation Jet-Cooled Rotational Study. Astrophys. J. 2018, 861, 70. [Google Scholar] [CrossRef]
  25. Koch, D.; Toubin, C.; Peslherbe, G.; Hynes, J. A Theoretical Study of the Formation of the Aminoacetonitrile Precursor of Glycine on Icy Grain Mantles in the Interstellar Medium. J. Phys. Chem. C 2008, 112, 2972–2980. [Google Scholar] [CrossRef]
  26. Ferris, J.P.; Ertem, G.; Agarwal, V.K. The Adsorption of Nucleotides and Polynucleotides on Montmorillonite Clay. Orig. Life Evol. Biosph. 1989, 19, 153–164. [Google Scholar] [CrossRef] [PubMed]
  27. Saladino, R.; Crestini, C.; Ciciriello, F.; Pino, S.; Costanzo, G.; Di Mauro, E. From Formamide to RNA: The Roles of Formamide and Water in the Evolution of Chemical Information. Res. Microbiol. 2009, 160, 441–448. [Google Scholar] [CrossRef]
  28. Jirásek, M.; Rickhaus, M.; Tejerina, L.; Anderson, H.L. Experimental and Theoretical Evidence for Aromatic Stabilization Energy in Large Macrocycles. J. Am. Chem. Soc. 2021, 143, 2403–2412. [Google Scholar] [CrossRef] [PubMed]
  29. Saladino, R.; Crestini, C.; Ciciriello, F.; Costanzo, G.; Di Mauro, E. Formamide Chemistry and the Origin of Informational Polymers. Chem. Biodivers. 2007, 4, 694–720. [Google Scholar] [CrossRef]
  30. Ruiz-Bermejo, M.; de la Fuente, J.L.; Pérez-Fernández, C.; Mateo-Martí, E. A Comprehensive Review of HCN-Derived Polymers. Processes 2021, 9, 597. [Google Scholar] [CrossRef]
  31. Villafañe-Barajas, S.A.; Ruiz-Bermejo, M.; Rayo-Pizarroso, P.; Colín-García, M. Characterization of HCN-Derived Thermal Polymer: Implications for Chemical Evolution. Processes 2020, 8, 968. [Google Scholar] [CrossRef]
  32. Breitkreuz, C.F.; Burger, J.; Hasse, H. Solubility of Formaldehyde in Mixtures of Water + Methanol + Poly(Oxymethylene) Dimethyl Ethers. Fluid Phase Equilibria 2023, 565, 113658. [Google Scholar] [CrossRef]
  33. Gkotsinas, A.; Guilbert-Lepoutre, A.; Raymond, S.N.; Nesvorny, D. Thermal Processing of Jupiter-Family Comets during Their Chaotic Orbital Evolution. Astrophys. J. 2022, 928, 43. [Google Scholar] [CrossRef]
  34. Fulle, M.; Molaro, P.; Rotundi, A.; Tonietti, L.; Aletti, A.; Buzzi, L.; Valisa, P. Alkali phenoxides in comets. arXiv 2025, arXiv:2506.02343. [Google Scholar] [CrossRef]
  35. Vázquez-Salazar, A.; Muñoz-Velasco, I. Evolutionary Routes to Modern Metabolic Pathways. Macromol 2023, 5, 23. [Google Scholar] [CrossRef]
  36. Muñoz-Velasco, I.; Cruz-González, A.; Hernández-Morales, R.; Campillo-Balderas, J.A.; Cottom-Salas, W.; Jácome, R.; Vázquez-Salazar, A. Pioneering role of RNA in the early evolution of life. Genet. Mol. Biol. 2024, 47 (Suppl. 1), e20240028. [Google Scholar] [CrossRef]
Universe 11 00349 g001
Figure 1. Thermodynamic feasibility matrix of key prebiotic reactions across cometary environments. Each reaction is mapped onto representative thermal regimes of different comet types: Oort Cloud comets (~50 K), Jupiter-family comets (~200 K), and sungrazers (~1000 K). Structural formulas of reactants and products are shown within each cell. Cell colors indicate the thermodynamic favorability of the reactions based on computed ΔG: green = exergonic ΔG < 0, yellow = thermodynamically neutral ΔG ≈ 0, red = endergonic ΔG > 0. Calculations are based on standard-state assumptions for isolated molecules; actual cometary environments may modify relative feasibility due to adsorption, surface interactions, or molecular mixtures. The figure should therefore be viewed as a baseline framework for thermodynamic trends, not as a comprehensive description of cometary chemistry.
Figure 1. Thermodynamic feasibility matrix of key prebiotic reactions across cometary environments. Each reaction is mapped onto representative thermal regimes of different comet types: Oort Cloud comets (~50 K), Jupiter-family comets (~200 K), and sungrazers (~1000 K). Structural formulas of reactants and products are shown within each cell. Cell colors indicate the thermodynamic favorability of the reactions based on computed ΔG: green = exergonic ΔG < 0, yellow = thermodynamically neutral ΔG ≈ 0, red = endergonic ΔG > 0. Calculations are based on standard-state assumptions for isolated molecules; actual cometary environments may modify relative feasibility due to adsorption, surface interactions, or molecular mixtures. The figure should therefore be viewed as a baseline framework for thermodynamic trends, not as a comprehensive description of cometary chemistry.
Universe 11 00349 g001
Universe 11 00349 g002
Figure 2. The plot reports the calculated Gibbs free energy variation (ΔG, kcal mol−1) between 50 and 1000 K for key reaction steps. Temperature increases from left to right according to the color gradient (from blue to red).
Figure 2. The plot reports the calculated Gibbs free energy variation (ΔG, kcal mol−1) between 50 and 1000 K for key reaction steps. Temperature increases from left to right according to the color gradient (from blue to red).
Universe 11 00349 g002
Table 1. Thermodynamic parameters of organic molecules used for Gibbs free energy calculations of prebiotic reactions. a. AMP values refer to aqueous measurements and were assumed to approximate the solid-state thermodynamic properties for modeling purposes. b. standard gas-phase for CO were used since CO does not exist as a stable solid under typical cometary conditions. Where experimental data were unavailable, estimated values based on structurally analogous compounds or group contribution methods were employed. Cheméo database: www.chemeo.com. National Institute of Standards and Technology (NIST): www.nist.gov.
Table 1. Thermodynamic parameters of organic molecules used for Gibbs free energy calculations of prebiotic reactions. a. AMP values refer to aqueous measurements and were assumed to approximate the solid-state thermodynamic properties for modeling purposes. b. standard gas-phase for CO were used since CO does not exist as a stable solid under typical cometary conditions. Where experimental data were unavailable, estimated values based on structurally analogous compounds or group contribution methods were employed. Cheméo database: www.chemeo.com. National Institute of Standards and Technology (NIST): www.nist.gov.
CompoundStructureΔH°f Gas (kcal/mol)ΔH°f Solid (kcal/mol)ΔH_Sub (kcal/mol)S° (cal/mol·K)Reference
AminoacetonitrileUniverse 11 00349 i001+27.26+17.42+9.84+75 (estimated)Cheméo database
AdenineUniverse 11 00349 i002NA+23.07NA+36.10Cheméo database
FormamideUniverse 11 00349 i003−44.45−61.59+17.14+45 (estimated)NIST Chemistry WebBook, SRD69
CyanamideUniverse 11 00349 i004+32.03+14.06+17.97+45 (estimated)NIST Chemistry WebBook, SRD 69
GlycolaldehydeUniverse 11 00349 i005−77.07−87.46+10.39+55 (estimated)Cheméo databse
2-aminooxazoleUniverse 11 00349 i006NA+20 (estimated)NA+60 (estimated)Estimed
FormaldehydeUniverse 11 00349 i007−27.7−30.7+3.0 (estimated)+40 (estimated)NIST Chemistry WebBook, SRD 69
RiboseUniverse 11 00349 i008NA−250.77NA+100 (estimated)NIST Chemistry WebBook, SRD 69
AdenosineUniverse 11 00349 i009NA−156.24NA+69.19[23]
Adenosine monophosphate (AMP) (a)Universe 11 00349 i010NA−379.30 (assumed)NA+97.36[23]
Carbon Monoxide (CO) (b)Universe 11 00349 i011−26.4NANA+47.3NIST Chemistry WebBook, SRD 69NIST
Cyanidric Acid (HCN)Universe 11 00349 i012+32.3+28.7+3.6+30 (estimated)NIST Chemistry WebBook, SRD 69
Table 2. Calculated ΔG values for each reaction pathway analyzed in this study under cometary cryogenic conditions.
Table 2. Calculated ΔG values for each reaction pathway analyzed in this study under cometary cryogenic conditions.
ReactionΔG50K (kcal/mol)ΔG100K (kcal/mol)ΔG150K (kcal/mol)ΔG200K (kcal/mol)ΔG250K (kcal/mol)ΔG300K (kcal/mol)ΔG400K (kcal/mol)ΔG600K (kcal/mol)ΔG800K (kcal/mol)ΔG1000K (kcal/mol)
Aminoacetonitrile ⇌ Adenine + H2O−402.5−405.0−407.5−410.0−412.5−415.0−420.0−430.0−440.0−450.0
Formamide ⇌ Adenine + CO + H2O−26.8−28.5−30.3−32.0−33.8−35.5−39.0−46.0−53.0−60.0
HCN polymer ⇌ Adenine−92.0−94.0−96.0−98.0−100.0−102.0−106.0−114.0−122.0−130.0
Cyanamide + Glycolaldehyde ⇌ 2-aminooxazole + H2O+22.8+20.5+18.3+16.0+13.8+11.5+7.0−2.0−11.0−20.0
5 H2CO ⇌ Ribose−71.5−73.0−74.5−76.0−77.5−79.0−82.0−88.0−94.0−100.0
Adenine + Ribose ⇌ Adenosine + H2O+4.5+4.0+3.5+3.0+2.5+2.0+1.0−1.0−3.0−5.0
Adenosine + H3PO4 ⇌ AMP + H2O+69.0+68.0+67.0+66.0+65.0+64.0+62.0+58.0+54.0+50.0
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Tonietti, L. Thermodynamic Assessment of Prebiotic Molecule Formation Pathways on Comets. Universe 2025, 11, 349. https://doi.org/10.3390/universe11100349

AMA Style

Tonietti L. Thermodynamic Assessment of Prebiotic Molecule Formation Pathways on Comets. Universe. 2025; 11(10):349. https://doi.org/10.3390/universe11100349

Chicago/Turabian Style

Tonietti, Luca. 2025. "Thermodynamic Assessment of Prebiotic Molecule Formation Pathways on Comets" Universe 11, no. 10: 349. https://doi.org/10.3390/universe11100349

APA Style

Tonietti, L. (2025). Thermodynamic Assessment of Prebiotic Molecule Formation Pathways on Comets. Universe, 11(10), 349. https://doi.org/10.3390/universe11100349

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop