Late-stage Ligand Modification After Coordination Strengthens Stereoselectively Self-Assembled Hemiaminal Ether Complexes.

Fragile hemiaminal ether linkages present in the backbone of koneramines (LR OR'), tridentate ligands, bound to copper(II) in stereoselectively self-assembled syn-[Cu(LR OR')X2 ] complexes were transformed into sturdy methylene linkages to make corresponding rac-[Cu(LR H)Cl2 ] complexes by late-stage ligand modification after coordination with the retention of coordination sphere. The generality of stereoselective self-assembly of koneramine complexes is shown by utilising a number of metal ions, anions, amines, alcohols and thiols with complete characterisations.

Formation of Amino Acids and Carboxylic Acids in Weakly Reducing Planetary Atmospheres by Solar Energetic Particles from the Young Sun.

Life most likely started during the Hadean Eon; however, the environmental conditions which contributed to the complexity of its chemistry are poorly known. A better understanding of various environmental conditions, including global (heliospheric) and local (atmospheric, surface, and oceanic), along with the internal dynamic conditions of the early Earth, are required to understand the onset of abiogenesis. Herein, we examine the contributions of galactic cosmic rays (GCRs) and solar energetic particles (SEPs) associated with superflares from the young Sun to the formation of amino acids and carboxylic acids in weakly reduced gas mixtures representing the early Earth's atmosphere. We also compare the products with those introduced by lightning events and solar ultraviolet light (UV). In a series of laboratory experiments, we detected and characterized the formation of amino acids and carboxylic acids via proton irradiation of a mixture of carbon dioxide, methane, nitrogen, and water in various mixing ratios. These experiments show the detection of amino acids after acid hydrolysis when 0.5% (v/v) of initial methane was introduced to the gas mixture. In the set of experiments with spark discharges (simulation of lightning flashes) performed for the same gas mixture, we found that at least 15% methane was required to detect the formation of amino acids, and no amino acids were detected in experiments via UV irradiation, even when 50% methane was used. Carboxylic acids were formed in non-reducing gas mixtures (0% methane) by proton irradiation and spark discharges. Hence, we suggest that GCRs and SEP events from the young Sun represent the most effective energy sources for the prebiotic formation of biologically important organic compounds from weakly reducing atmospheres. Since the energy flux of space weather, which generated frequent SEPs from the young Sun in the first 600 million years after the birth of the solar system, was expected to be much greater than that of GCRs, we conclude that SEP-driven energetic protons are the most promising energy sources for the prebiotic production of bioorganic compounds in the atmosphere of the Hadean Earth.

Impact of M Dwarfs Ultraviolet Radiation on Prebiotic Chemistry: The Case of Adenine.

To date, several exoplanets have been found to orbit within the habitable zone of main sequence M stars (M dwarfs). These stars exhibit different levels of chromospheric activity that produces ultraviolet (UV) radiation. UV may be harmful to life, but it can also trigger reactions of prebiotic importance on the surface of a potentially habitable planet (PHP). We created a code to obtain the adenine yield for a known adenine synthesis route from diaminomaleonitrile (DAMN). We used computational methods to calculate the reaction coefficient rates (photolysis rate J and rate constant K) for the intermediate molecules DAMN, diaminofumaronitrile (DAFN), and 4-aminoimidazole-5-carbonitrile (AICN) of the adenine synthesis route. We used stellar UV sources and a mercury lamp to compare the theoretical results with experiments performed with lamps. The surface UV flux of planets in the habitable zone of two active M dwarfs (Proxima Centauri and AD Leonis) and the prebiotic Earth was calculated using the photochemical model ATMOS, considering a CO2-N2-H2O atmosphere. We obtained UV absorption coefficients for DAMN and DAFN and thermodynamic parameters that are useful for prebiotic chemistry studies. According to our results, experiments using UV lamps may underestimate the photolysis production of molecules of prebiotic importance. Our results indicate that photolysis reactions are fast with a yield of 50% of AICN in 10 s for the young Sun and ∼1 h for Proxima Centauri b. Planets around active M dwarfs may provide the most favorable environment for UV-mediated production of compounds relevant to the origins of life. The kinetic reaction AICN + HCN  adenine is the bottleneck of the pathway with reaction rates <10-22 L/(mol·s).

Spark of Life: Role of Electrotrophy in the Emergence of Life.

The emergence of life has been a subject of intensive research for decades. Different approaches and different environmental "cradles" have been studied, from space to the deep sea. Since the recent discovery of a natural electrical current through deep-sea hydrothermal vents, a new energy source is considered for the transition from inorganic to organic. This energy source (electron donor) is used by modern microorganisms via a new trophic type, called electrotrophy. In this review, we draw a parallel between this metabolism and a new theory for the emergence of life based on this electrical electron flow. Each step of the creation of life is revised in the new light of this prebiotic electrochemical context, going from the evaluation of similar electrical current during the Hadean, the CO2 electroreduction into a prebiotic primordial soup, the production of proto-membranes, the energetic system inspired of the nitrate reduction, the proton gradient, and the transition to a planktonic proto-cell. Finally, this theory is compared to the two other theories in hydrothermal context to assess its relevance and overcome the limitations of each. Many critical factors that were limiting each theory can be overcome given the effect of electrochemical reactions and the environmental changes produced.

Photochemical Synthesis of Ammonia and Amino Acids from Nitrous Oxide.

Abiotic synthesis of ammonia (NH3) and amino acids is important for the origin of life and early evolution. Ammonia and organic nitrogen species may be produced from nitrous oxide (N2O), which is a second abundant nitrogen species in the atmosphere. Here, we report a new photochemical experiment and evaluate whether N2O can be used as a nitrogen source for prebiotic synthesis in the atmosphere. We conducted a series of experiments by using a gas mixture of N2O+CO, N2O+CO2, or N2O + H2 in the presence of liquid water. The results demonstrate that NH3, methylamine (CH3NH2), and some amino acids such as glycine, alanine, and serine can be synthesized through photochemistry from N2O even without metal catalysts. NH3 can be produced not only from CO + N2O, but also from H2+N2O. Glycine can be synthesized from CH3NH2 and CO2, which can be produced from N2O and CO under ultraviolet irradiation. Our work demonstrates, for the first time, that N2O could be an important nitrogen source and provide a new process for synthesizing ammonia and organic nitrogen species, which has not been previously considered. The contribution of organic synthesis from N2O should, therefore, be considered when discussing the prebiotic chemistry on primitive Earth.

Super-Robust Xanthine-Sodium Complexes on Au(111).

A widely accepted theory is that life originated from the hydrothermal environment in the primordial ocean. Nevertheless, the low desorption temperature from inorganic substrates and the fragileness of hydrogen-bonded nucleobases do not support the required thermal stability in such an environment. Herein, we report the super-robust complexes of xanthine, one of the precursors for the primitive nucleic acids, with Na. We demonstrate that the well-defined xanthine-Na complexes can only form when the temperature is ≥430 K, and the complexes keep adsorbed even at ≈720 K, presenting as the most thermally stable organic polymer ever reported on Au(111). This work not only justifies the necessity of high-temperature, Na-rich environment for the prebiotic biosynthesis but also reveals the robustness of the xanthine-Na complexes upon the harsh environment. Moreover, the complexes can induce significant electron transfer with the metal as inert as Au and hence lift the Au atoms up.

Computational Analysis of a Prebiotic Amino Acid Synthesis with Reference to Extant Codon-Amino Acid Relationships.

Novel density functional theory calculations are presented regarding a mechanism for prebiotic amino acid synthesis from alpha-keto acids that was suggested to happen via catalysis by dinucleotide species. Our results were analysed with comparison to the original hypothesis (Copley et al., PNAS, 2005, 102, 4442-4447). It was shown that the keto acid-dinucleotide hypothesis for possible prebiotic amino acid synthesis was plausible based on an initial computational analysis, and details of the structures for the intermediates and transition states showed that there was wide scope for interactions between the keto acid and dinucleotide moieties that could affect the free energy profiles and lead to the required proto-metabolic selectivity.

The Prebiotic Kitchen: A Guide to Composing Prebiotic Soup Recipes to Test Origins of Life Hypotheses.

"Prebiotic soup" often features in discussions of origins of life research, both as a theoretical concept when discussing abiological pathways to modern biochemical building blocks and, more recently, as a feedstock in prebiotic chemistry experiments focused on discovering emergent, systems-level processes such as polymerization, encapsulation, and evolution. However, until now, little systematic analysis has gone into the design of well-justified prebiotic mixtures, which are needed to facilitate experimental replicability and comparison among researchers. This paper explores principles that should be considered in choosing chemical mixtures for prebiotic chemistry experiments by reviewing the natural environmental conditions that might have created such mixtures and then suggests reasonable guidelines for designing recipes. We discuss both "assembled" mixtures, which are made by mixing reagent grade chemicals, and "synthesized" mixtures, which are generated directly from diversity-generating primary prebiotic syntheses. We discuss different practical concerns including how to navigate the tremendous uncertainty in the chemistry of the early Earth and how to balance the desire for using prebiotically realistic mixtures with experimental tractability and replicability. Examples of two assembled mixtures, one based on materials likely delivered by carbonaceous meteorites and one based on spark discharge synthesis, are presented to illustrate these challenges. We explore alternative procedures for making synthesized mixtures using recursive chemical reaction systems whose outputs attempt to mimic atmospheric and geochemical synthesis. Other experimental conditions such as pH and ionic strength are also considered. We argue that developing a handful of standardized prebiotic recipes may facilitate coordination among researchers and enable the identification of the most promising mechanisms by which complex prebiotic mixtures were "tamed" during the origin of life to give rise to key living processes such as self-propagation, information processing, and adaptive evolution. We end by advocating for the development of a public prebiotic chemistry database containing experimental methods (including soup recipes), results, and analytical pipelines for analyzing complex prebiotic mixtures.

Cyclic Dipeptides Formation From Linear Dipeptides Under Potentially Prebiotic Earth Conditions.

Cyclic dipeptides (DKPs) are peptide precursors and chiral catalysts in the prebiotic process. This study reports proline-containing DKPs that were spontaneously obtained from linear dipeptides under an aqueous solution. Significantly, the yields of DKPs were affected by the sequence of linear dipeptides and whether the reaction contains trimetaphosphate. These findings provide the possibility that DKPs might play a key role in the origin of life.

Histidine Self-assembly and Stability on Mineral Surfaces as a Model of Prebiotic Chemical Evolution: An Experimental and Computational Approach.

The abiotic synthesis of histidine under experimental prebiotic conditions has proven to be chemically promising and plausible. Within this context, the present results suggest that histidine amino acid may function as a simple prebiotic catalyst able to enhance amino acid polymerization. This work describes an experimental and computational approach to the self-assembly and stabilization of DL-histidine on mineral surfaces using antigorite ((Mg, Fe)3Si2O5(OH)4), pyrite (FeS2), and aragonite (CaCO3) as representative minerals of prebiotic scenarios, such as meteorites, and subaerial and submarine hydrothermal systems. Experimental results were obtained through polarized-light microscopy, IR spectroscopy (ATR-FTIR), and differential scanning calorimetry (DSC). Molecular dynamics was performed through computational simulations with the MM + method in HyperChem software. IR spectra suggest the presence of peptide bonds in the antigorite-histidine and aragonite-histidine assemblages with the presence of amide I and amide II vibration bands. The FTIR second derivative inspection supports this observation. Moreover, DSC data shows histidine stabilization in the presence of antigorite and aragonite by changes in histidine thermodynamic properties, particularly an increase in histidine decomposition temperature (272ºC in antigorite and 275ºC in aragonite). Results from molecular dynamics are consistent with DSC data, suggesting an antigorite-histidine closer interaction with decreased molecular distances (cca. 5.5 Å) between the amino acid and the crystal surface. On the whole, the experimental and computational outcomes support the role of mineral surfaces in prebiotic chemical evolution as enhancers of organic stability.

Silicate-, Magnesium Ion-, and Urea-Induced Prebiotic Phosphorylation of Uridine via Pyrophosphate; Revisiting the Hot Drying Water Pool Scenario.

The availability of nucleotides on the early Earth is of great significance for the origin of a self-replicating system capable of undergoing evolution. We hereby report the successful phosphorylation reactions of the nucleoside uridine under heating in the "drying pool" prebiotic model at temperatures ranging from 60-75 °C, and by using pyrophosphate as a phosphorylation agent. Uridine monophosphates (UMP) such as uridine-5'-monophosphate (5'-UMP), 2'-UMP, and 3'-UMP, as well as cyclic 2'-3'-UMP, were identified by 31P-NMR. In addition to the above-mentioned products, a dimer of uridine-phosphate-uridine (U-P-U) was also observed. The reactions were promoted by white quartz sand, Mg2+, and by using urea as a condensation agent. The reactions also proceeded without this mixture; however, the yields increased remarkably with the presence of the above-mentioned materials. The results suggest that a hot/evaporating-drying pool of water containing organics, salts, and reactive phosphorus could be sufficient to form significant phosphate esters.

The kinetics and mechanisms of reactions in the flow systems glycine-sodium trimetaphosphate-imidazoles: the crucial role of imidazoles in prebiotic peptide syntheses.

The kinetics of oligopeptides formation in the flow systems glycine-sodium trimetaphosphate-imidazole/N-methylimidazole at thermocyclic regime has been investigated by HPLC and 31P NMR methods in the ranges of temperature from 45 to 90 °C and pH from 8.5 to 11.5. Detailed reaction mechanisms have been proposed and justified by quantum chemical calculations using DFT method at the CAM-B3LYP/TZVP level with accounting solvent effect by the C-PCM model. A new imidazole catalysis mechanism by which imidazole reacts with cyclic N,O-phosphoryl glycine giving N-imidazolyl-O-glycyl phosphate as a key intermediate was proposed and validated. It is emphasized that while in the absence of imidazoles, prebiotic activation of amino acids occurs at the N-terminus, in the presence of imidazoles it shifts to the O-terminus. This means that in the peptide elongation N-imidazolyl-O-aminoacyl phosphates play in prebiotic systems the outstanding role similar to that of aminoacyl adenylates formed at the ATP and aminoacyl-tRNA synthetases presence in biosystems. The new crucial role of imidazoles in prebiotic evolution has been noticed. The systems used and modes of their conversion can be good models for prebiotic peptide syntheses in a flow thermocyclic regime.

Formic Acid, a Ubiquitous but Overlooked Component of the Early Earth Atmosphere.

Terrestrial volcanism has been one of the dominant geological forces shaping our planet since its earliest existence. Its associated phenomena, like atmospheric lightning and hydrothermal activity, provide a rich energy reservoir for chemical syntheses. Based on our laboratory simulations, we propose that on the early Earth volcanic activity inevitably led to a remarkable production of formic acid through various independent reaction channels. Large-scale availability of atmospheric formic acid supports the idea of the high-temperature accumulation of formamide in this primordial environment.

Computer and Experimental Simulation of Alloxazine Synthesis from Gamma Irradiation of Amino Acids on Iceland Spar: A Prebiotic Chemistry Perspective.

On ancient Earth, environmental conditions favored prebiotic chemical reactions. In the Archean, some molecules with conjugated rings might have been synthesized, displaying structural stability in the Archean in the presence of ionizing radiation and hydration-dehydration events. Additionally, it is suggested that on ancient Earth, calcite was a common mineral promoting organic compound synthesis. In the present work a study of the interaction of amino acid mixtures with the (104) surface of calcite is presented. Our preliminary results show the abiotic synthesis of alloxazine (a flavin with relevant photochemical properties). Computer simulations were performed in HyperChem 8.0.1. by means of MM+ molecular mechanics and PM3 semi-empirical methods, in 27 possible amino acid trimers of alanine, glycine and lysine. Alloxazine formation is possible by the gamma irradiation of amino acids. The computer simulations show that trimers GGG and GGA promote the further transformation from diketopiperazines (DKP's) and KGK to alloxazine. The computer simulations with free radicals are not stable when alloxazine is interacting with the calcite surface. Experiments in anoxygenic environments with hydration-dehydration events in gamma irradiated samples allow the abiotic formation of flavins, DKP's and a heterocycle compound with possible relevance in prebiotic chemistry.

Accuracy of Thermodynamic Databases for Hydroxyapatite Dissolution Constant.

Discrepancies have been noted in the solubility constant values of calcium phosphate minerals between various databases employed in widely used aqueous speciation calculation software programs. This can cause serious errors in the calculated speciation of waters when using these software programs. The aim of this communication was to bring to light these discrepancies. Experimental determinations of the hydroxyapatite (HAP) solubility product vary by as much as 10 orders of magnitude as a result of experimental challenges related to the presence of impurities in the HAP used, incongruent dissolution, and the contamination of solutions with dissolved carbon dioxide. It is suggested that the value used in the database Thermo.dat is consistent with experimental data devoid of common experimental problems, whereas other common databases use values that lead to a vastly overestimated solubility of HAP.

Structural and Energetic Compatibility: The Driving Principles of Molecular Evolution.

In this work, we provide an answer to the question formulated by Albert Eschenmoser: "How would you envisage the bridge between potentially primordial geochemistry that had been disordered and one that gradually became self-organizing?" Analysis of the free-energy profiles of some of the key reactions leading to formation of nucleotides and their oligomers shows that, whereas the first part of the pathway, up to nucleotides, is energy-driven, in the second low-energy part entropic control in the form of structural compatibility becomes more important. We suggest that the birth of modern metabolism requires structural compatibility, which is enabled by the commensurability of the thermodynamics of the synthetic steps with the stabilizing effect of those intermolecular interactions that play a key role in dictating entropic control of these reactions.

Comet Pond II: Synergistic Intersection of Concentrated Extraterrestrial Materials and Planetary Environments to Form Procreative Darwinian Ponds.

In the “comet pond” model, a rare combination of circumstances enables the entry and landing of pristine organic material onto a planetary surface with the creation of a pond by a soft impact and melting of entrained ices. Formation of the constituents of the comet in the cold interstellar medium and our circumstellar disk results in multiple constituents at disequilibrium which undergo rapid chemical reactions in the warmer, liquid environment. The planetary surface also provides minerals and atmospheric gases which chemically interact with the pond’s organic- and trace-element-rich constituents. Pond physical morphology and the heterogeneities imposed by gravitational forces (bottom sludge; surface scum) and weather result in a highly heterogeneous variety of macro- and microenvironments. Wet/dry, freeze/thaw, and natural chromatography processes further promote certain reaction sequences. Evaporation concentrates organics less volatile than water. Freezing concentrates all soluble organics into a residual liquid phase, including CH3OH, HCN, etc. The pond’s evolutionary processes culminate in the creation of a Macrobiont with the metabolically equivalent capabilities of energy transduction and replication of RNA (or its progenitor informational macromolecule), from which smaller organisms can emerge. Planet-wide dispersal of microorganisms is achieved through wind transport, groundwater, and/or spillover from the pond into surface hydrologic networks.

A Direct Prebiotic Synthesis of Nicotinamide Nucleotide.

The "RNA World" hypothesis proposes an early episode of the natural history of Earth, where RNA was used as the only genetically encoded molecule to catalyze steps in its metabolism. This, according to the hypothesis, included RNA catalysts that used RNA cofactors. However, the RNA World hypothesis places special demands on prebiotic chemistry, which must now deliver not only four ribonucleosides, but also must deliver the "functional" portion of these RNA cofactors. While some (e.g., methionine) present no particular challenges, nicotinamide ribose is special. Essential to its role in biological oxidations and reductions, its glycosidic bond that holds a positively charged heterocycle is especially unstable with respect to cleavage. Nevertheless, we are able to report here a prebiotic synthesis of phosphorylated nicotinamide ribose under conditions that also conveniently lead to the adenosine phosphate components of this and other RNA cofactors.

Prebiotic stereoselective synthesis of purine and noncanonical pyrimidine nucleotide from nucleobases and phosphorylated carbohydrates.

According to a current "RNA first" model for the origin of life, RNA emerged in some form on early Earth to become the first biopolymer to support Darwinism here. Threose nucleic acid (TNA) and other polyelectrolytes are also considered as the possible first Darwinian biopolymer(s). This model is being developed by research pursuing a "Discontinuous Synthesis Model" (DSM) for the formation of RNA and/or TNA from precursor molecules that might have been available on early Earth from prebiotic reactions, with the goal of making the model less discontinuous. In general, this is done by examining the reactivity of isolated products from proposed steps that generate those products, with increasing complexity of the reaction mixtures in the proposed mineralogical environments. Here, we report that adenine, diaminopurine, and hypoxanthine nucleoside phosphates and a noncanonical pyrimidine nucleoside (zebularine) phosphate can be formed from the direct coupling reaction of cyclic carbohydrate phosphates with the free nucleobases. The reaction is stereoselective, giving only the ß-anomer of the nucleotides within detectable limits. For purines, the coupling is also regioselective, giving the N-9 nucleotide for adenine as a major product. In the DSM, phosphorylated carbohydrates are presumed to have been available via reactions explored previously [Krishnamurthy R, Guntha S, Eschenmoser A (2000) Angew Chem Int Ed 39:2281-2285], while nucleobases are presumed to have been available from hydrogen cyanide and other nitrogenous species formed in Earth's primitive atmosphere.

Chemical systems, chemical contiguity and the emergence of life.

Charting the emergence of living cells from inanimate matter remains an intensely challenging scientific problem. The complexity of the biochemical machinery of cells with its exquisite intricacies hints at cells being the product of a long evolutionary process. Research on the emergence of life has long been focusing on specific, well-defined problems related to one aspect of cellular make-up, such as the formation of membranes or the build-up of information/catalytic apparatus. This approach is being gradually replaced by a more "systemic" approach that privileges processes inherent to complex chemical systems over specific isolated functional apparatuses. We will summarize the recent advances in system chemistry and show that chemical systems in the geochemical context imply a form of chemical contiguity in the syntheses of the various molecules that precede modern biomolecules.