Alkaline saline lakes: A chemical evolution experiment evaluating the stability of formaldehyde in an aqueous saline environment.

Formaldehyde condensation in the presence of a mineral catalyst and under alkaline conditions is considered to be a "messy" chemical system due to its dependence on the complex chemical equilibrium between the reaction intermediates, which has a significant impact on the final products. This chemical system is extremely important in prebiotic chemistry and has been proposed as a potential pathway for carbohydrate formation in the early Earth. Saline and soda lakes are alkaline systems that could concentrate and accumulate a wide variety of ions (such as phosphate) and clay minerals, which can catalyze prebiotic chemical reactions. These geological environments have recently been suggested as ideal environments in which prebiotic chemical reactions could have occurred. This study uses Lake Alchichica in Mexico as a physicochemical analog of an early Archean saline lake to examine the stability of formaldehyde in these aqueous saline environments. Formaldehyde decomposes into sugar-like and CHO molecules in alkaline, high-salinity environments depending on the minerals phases present. As phosphate ion (HPO4 2-) is available in the aqueous medium, the results of our experiments also imply that phosphorylation processes may have occurred in these natural settings.

Stem Life: A Framework for Understanding the Prebiotic-Biotic Transition.

Abiogenesis is frequently envisioned as a linear, ladder-like progression of increasingly complex chemical systems, eventually leading to the ancestors of extant cellular life. This "pre-cladistics" view is in stark contrast to the well-accepted principles of organismal evolutionary biology, as informed by paleontology and phylogenetics. Applying this perspective to origins, I explore the paradigm of "Stem Life," which embeds abiogenesis within a broader continuity of diversification and extinction of both hereditary lineages and chemical systems. In this new paradigm, extant life's ancestral lineage emerged alongside and was dependent upon many other complex prebiotic chemical systems, as part of a diverse and fecund prebiosphere. Drawing from several natural history analogies, I show how this shift in perspective enriches our understanding of Origins and directly informs debates on defining Life, the emergence of the Last Universal Common Ancestor (LUCA), and the implications of prebiotic chemical experiments.

Carbon- and Nitrogen-Based Complexes as Photocatalysts for Prebiotic and Oxygen Chemistry during Earth Evolution.

Sunlight has long served as primary energy source on our planet, shaping the behavior of living organisms. Extensive research has been dedicated to unraveling the evolutionary pathways involved. When the formation of Earth atmosphere, it primarily consisted of small gas molecules, which are considered crucial for the emergence of life. Recent demonstrations have shown that these molecules can also be transformed into semiconductors, with the potential to harness solar energy and catalyze chemical reactions as photocatalysts. Building upon this research, this minireview focuses on the potential revolutionary impact of photocatalysis on Earth. Initially, it examines key reactions, such as the formation of prebiotic molecules and the oxygen evolution reaction via water oxidation. Additionally, various C-N complexes in photocatalysts are explored, showcasing their roles in catalyzing chemical reactions. The conclusion and outlook provide a potential pathway for the evolution of Earth, shedding light on the significance of metal-free photocatalysts in development of Earth.

From Meteorite to Life's Building Blocks: A possible Electrochemical Pathway to Amino Acids and Peptide Bonds.

This study explores the electrochemical properties of the carbonaceous Allende CV3 meteorite, focusing on its potential as a Fe-based catalyst derived from Mackinawite iron sulfide for electrocatalytic reactions facilitating nitrogen (N2) fixation into ammonia. Through comprehensive analysis, we not only monitored the evolution of key compounds such as CN-, sulfur/H2S, H2 and carbonyl compounds, but also identified potential reagent carriers, indicating significant implications for the Strecker synthesis of amino acids in space environments. Initial examination revealed the presence of polypeptides, notably sequences including trimer Gly3, pentamer Gly3-Ala2, and hexamer Gly4-(HO-Gly)2. These discoveries greatly enhance our understanding of astrobiological chemistry, offering valuable insights into prebiotic processes and the potential presence of life-building blocks throughout the universe.

Exploring the Core Formose Cycle: Catalysis and Competition.

The core autocatalytic cycle of the formose reaction may be enhanced or eroded by the presence of simple molecules at life's origin. Utilizing quantum chemistry, we calculate the thermodynamics and kinetics of reactions both within the core cycle and those that deplete the reactants and intermediates, such as the Cannizzaro reaction. We find that via disproportionation of aldehydes into carboxylic acids and alcohols, the Cannizzaro reaction furnishes simple catalysts for a variety of reactions. We also find that ammonia can catalyze both in-cycle and Cannizzaro reactions while hydrogen sulfide does not; both, however, play a role in sequestering reactants and intermediates in the web of potential reactions.

Photochemically Driven Peptide Formation in Supersaturated Aerosol Droplets.

The condensation of amino acids into peptides plays a crucial role in protein synthesis and is thus essential for understanding the origins of life. However, the spontaneous formation of peptides from amino acids in bulk aqueous media is energetically unfavorable, posing a challenge for elucidating plausible abiotic mechanisms. In this study, we investigate the formation of amide bonds between amino acids within highly supersaturated aerosol droplets containing dicyandiamide (DCD), a cyanide derivative potentially present on primordial Earth. Metastable states, i.e. supersaturation, within individual micron-sized droplets are studied using both an optical trap and a linear quadrupole electrodynamic balance. When irradiated with intense visible light, amide bond formation is observed to occur and can be monitored using vibrational bands in Raman spectra. The reaction rate is found to be strongly influenced by droplet size and kinetic modelling suggests that it is driven by the photochemical product of a DCD self-reaction. Our results highlight the potential of atmospheric aerosol particles as reaction environments for peptide synthesis and have potential implications for the prebiotic chemistry of early Earth.

Ribosome-Free Translation up to Pentapeptides via Template Walk on RNA Sequences.

The origin of translation is one of the most difficult problems of molecular evolution. Identifying molecular systems that translate an RNA sequence into a peptide sequence in the absence of ribosomes and enzymes is a challenge. Recently, single-nucleotide translation via coupling of 5' phosphoramidate-linked amino acids to 2'/3'-aminoacyl transfer-NMPs, as directed by the sequence of an RNA template, was demonstrated for three of the four canonical nucleotides. How single-nucleotide translation could be expanded to include all four bases and to produce longer peptides without translocation along the template strand remained unclear. Using transfer strands of increasing length containing any of the four bases that interrogate adjacent positions along the template, we now show that pentapeptides can be produced in coupling reactions and subsequent hydrolytic release in situ. With 2'/3'-aminoacylated mono-, di-, tri- and tetranucleotides we thus show how efficient translation can be without biomacromolecules.

Prebiotic N-(2-Aminoethyl)-Glycine (AEG)-Assisted Synthesis of Proto-RNA?

Quantum mechanical calculations are used to explore the thermodynamics of possible prebiotic synthesis of the building blocks of nucleic acids. Different combinations of D-ribofuranose (Ribf) and N-(2-aminoethyl)-glycine (AEG) (trifunctional connectors (TCs)); the nature of the Ribf, its anomeric form, and its ring puckering (conformation); and the nature of the nucleobases (recognition units (RUs)) are considered. The combinatorial explosion of possible nucleosides has been drastically reduced on physicochemical grounds followed by a detailed thermodynamic evaluation of alternative synthetic pathways. The synthesis of nucleosides containing N-(2-aminoethyl)-glycine (AEG) is predicted to be thermodynamically favored suggesting a possible role of AEG as a component of an ancestral proto-RNA that may have preceded today's nucleic acids. A new pathway for the building of free nucleotides (exemplified by 5'-uridine monophosphate (UMP)) and of AEG dipeptides is proposed. This new pathway leads to a spontaneous formation of free UMP assisted by an AEG nucleoside in an aqueous environment. This appears to be a workaround to the "water problem" that prohibits the synthesis of nucleotides in water.

The Pigment World: Life's Origins as Photon-Dissipating Pigments.

Many of the fundamental molecules of life share extraordinary pigment-like optical properties in the long-wavelength UV-C spectral region. These include strong photon absorption and rapid (sub-pico-second) dissipation of the induced electronic excitation energy into heat through peaked conical intersections. These properties have been attributed to a "natural selection" of molecules resistant to the dangerous UV-C light incident on Earth's surface during the Archean. In contrast, the "thermodynamic dissipation theory for the origin of life" argues that, far from being detrimental, UV-C light was, in fact, the thermodynamic potential driving the dissipative structuring of life at its origin. The optical properties were thus the thermodynamic "design goals" of microscopic dissipative structuring of organic UV-C pigments, today known as the "fundamental molecules of life", from common precursors under this light. This "UV-C Pigment World" evolved towards greater solar photon dissipation through more complex dissipative structuring pathways, eventually producing visible pigments to dissipate less energetic, but higher intensity, visible photons up to wavelengths of the "red edge". The propagation and dispersal of organic pigments, catalyzed by animals, and their coupling with abiotic dissipative processes, such as the water cycle, culminated in the apex photon dissipative structure, today's biosphere.

A Prebiotic Pathway to Nicotinamide Adenine Dinucleotide.

Enzymes play a fundamental role in cellular metabolism. A wide range of enzymes require the presence of complementary coenzymes and cofactors to function properly. While coenzymes are believed to have been part of the last universal ancestor (LUCA) or have been present even earlier, the syntheses of crucial coenzymes like the redox-active coenzymes flavin adenine dinucleotide (FAD) or nicotinamide adenine dinucleotide (NAD+) remain challenging. Here, we present a pathway to NAD+ under prebiotic conditions starting with ammonia, cyanoacetaldehyde, prop-2-ynal and sugar-forming precursors, yielding in situ the nicotinamide riboside. Regioselective phosphorylation and water stable light activated adenosine monophosphate derivatives allow for topographically and irradiation-controlled formation of NAD+. Our findings indicate that NAD+, a coenzyme vital to life, can be formed non-enzymatically from simple organic feedstock molecules via photocatalytic activation under prebiotically plausible early Earth conditions in a continuous process under aqueous conditions.

UV Transmission in Prebiotic Environments on Early Earth.

Ultraviolet (UV) light is likely to have played important roles in surficial origins of life scenarios, potentially as a productive source of energy and molecular activation, as a selective means to remove unwanted side products, or as a destructive mechanism resulting in loss of molecules/biomolecules over time. The transmission of UV light through prebiotic waters depends upon the chemical constituents of such waters, but constraints on this transmission are limited. Here, we experimentally measure the molar decadic extinction coefficients for a number of small molecules used in various prebiotic synthetic schemes. We find that many small feedstock molecules absorb most at short (∼200 nm) wavelengths, with decreasing UV absorption at longer wavelengths. For comparison, we also measured the nucleobase adenine and found that adenine absorbs significantly more than the simpler molecules often invoked in prebiotic synthesis. Our results enable the calculation of UV photon penetration under varying chemical scenarios and allow further constraints on plausibility and self-consistency of such scenarios. While the precise path that prebiotic chemistry took remains elusive, improved understanding of the UV environment in prebiotically plausible waters can help constrain both the chemistry and the environmental conditions that may allow such chemistry to occur.

New Estimates of Nitrogen Fixation on Early Earth.

Fixed nitrogen species generated by the early Earth's atmosphere are thought to be critical to the emergence of life and the sustenance of early metabolisms. A previous study estimated nitrogen fixation in the Hadean Earth's N2/CO2-dominated atmosphere; however, that previous study only considered a limited chemical network that produces NOx species (i.e., no HCN formation) via the thermochemical dissociation of N2 and CO2 in lightning flashes, followed by photochemistry. Here, we present an updated model of nitrogen fixation on Hadean Earth. We use the Chemical Equilibrium with Applications (CEA) thermochemical model to estimate lightning-induced NO and HCN formation and an updated version of KINETICS, the 1-D Caltech/JPL photochemical model, to assess the photochemical production of fixed nitrogen species that rain out into the Earth's early ocean. Our updated photochemical model contains hydrocarbon and nitrile chemistry, and we use a Geant4 simulation platform to consider nitrogen fixation stimulated by solar energetic particle deposition throughout the atmosphere. We study the impact of a novel reaction pathway for generating HCN via HCN2, inspired by the experimental results which suggest that reactions with CH radicals (from CH4 photolysis) may facilitate the incorporation of N into the molecular structure of aerosols. When the HCN2 reactions are added, we find that the HCN rainout rate rises by a factor of five in our 1-bar case and is about the same in our 2- and 12-bar cases. Finally, we estimate the equilibrium concentration of fixed nitrogen species under a kinetic steady state in the Hadean ocean, considering loss by hydrothermal vent circulation, photoreduction, and hydrolysis. These results inform our understanding of environments that may have been relevant to the formation of life on Earth, as well as processes that could lead to the emergence of life elsewhere in the universe.

A Magnesium Binding Site And The Anomeric Effect Regulate The Abiotic Redox Chemistry Of Nicotinamide Nucleotides.

Nicotinamide adenine dinucleotide (NAD+) is a redox active molecule that is universally found in biology. Despite the importance and simplicity of this molecule, few reports exist that investigate which molecular features are important for the activity of this ribodinucleotide. By exploiting the nonenzymatic reduction and oxidation of NAD+ by pyruvate and methylene blue, respectively, we were able to identify key molecular features necessary for the intrinsic activity of NAD+ through kinetic analysis. Such features may explain how NAD+ could have been selected early during the emergence of life. Simpler molecules, such as nicotinamide, that lack an anomeric carbon are incapable of accepting electrons from pyruvate. The phosphate moiety inhibits activity in the absence of metal ions but facilitates activity at physiological pH and model prebiotic conditions by recruiting catalytic Mg2+. Reduction proceeds through consecutive single electron transfer events. Of the derivatives tested, including nicotinamide mononucleotide, nicotinamide riboside, 3-(aminocarbonyl)-1-(2,3-dihydroxypropyl)pyridinium, 1-methylnicotinamide, and nicotinamide, only NAD+ and nicotinamide mononucleotide would be capable of efficiently accepting and donating electrons within a nonenzymatic electron transport chain. The data are consistent with early metabolic chemistry exploiting NAD+ or nicotinamide mononucleotide and not simpler molecules.

Proto-neural networks from thermal proteins.

Proteinoids are synthetic polymers that have structural similarities to natural proteins, and their formation is achieved through the application of heat to amino acid combinations in a dehydrated environment. The thermal proteins, initially synthesised by Sidney Fox during the 1960s, has the ability to undergo self-assembly, resulting in the formation of microspheres that resemble cells. These microspheres have fascinating biomimetic characteristics. In recent studies, substantial advancements have been made in elucidating the electrical signalling phenomena shown by proteinoids, hence showcasing their promising prospects in the field of neuro-inspired computing. This study demonstrates the advancement of experimental prototypes that employ proteinoids in the construction of fundamental neural network structures. The article provides an overview of significant achievements in proteinoid systems, such as the demonstration of electrical excitability, emulation of synaptic functions, capabilities in pattern recognition, and adaptability of network structures. This study examines the similarities and differences between proteinoid networks and spontaneous neural computation. We examine the persistent challenges associated with deciphering the underlying mechanisms of emergent proteinoid-based intelligence. Additionally, we explore the potential for developing bio-inspired computing systems using synthetic thermal proteins in forthcoming times. The results of this study offer a theoretical foundation for the advancement of adaptive, self-assembling electronic systems that operate using artificial bio-neural principles.

Chapter 4: A Geological and Chemical Context for the Origins of Life on Early Earth.

Within the first billion years of Earth's history, the planet transformed from a hot, barren, and inhospitable landscape to an environment conducive to the emergence and persistence of life. This chapter will review the state of knowledge concerning early Earth's (Hadean/Eoarchean) geochemical environment, including the origin and composition of the planet's moon, crust, oceans, atmosphere, and organic content. It will also discuss abiotic geochemical cycling of the CHONPS elements and how these species could have been converted to biologically relevant building blocks, polymers, and chemical networks. Proposed environments for abiogenesis events are also described and evaluated. An understanding of the geochemical processes under which life may have emerged can better inform our assessment of the habitability of other worlds, the potential complexity that abiotic chemistry can achieve (which has implications for putative biosignatures), and the possibility for biochemistries that are vastly different from those on Earth.

The GARD Prebiotic Reproduction Model Described in Order and Complexity.

Early steps in the origin of life were necessarily connected to the unlikely formation of self-reproducing structures from chaotic chemistry. Simulations of chemical kinetics based on the graded autocatalysis replication domain (GARD) model demonstrate the ability of a micellar system to become self-reproducing units away from equilibrium. Even though they may be very rare in the initial state of the system, the property of their endogenous mutually catalytic networks being dynamic attractors greatly enhanced reproduction propensity, revealing their potential for selection and Darwinian evolution processes. In parallel, order and complexity have been shown to be crucial parameters in successful evolution. Here, we probe these parameters in the dynamics of GARD-governed entities in an attempt to identify characteristic mechanisms of their development in non-covalent molecular assemblies. Using a virtual random walk perspective, a value for consecutive order is defined based on statistical thermodynamics. The complexity, on the other hand, is determined by the size of a minimal algorithm fully describing the statistical properties of the random walk. By referring to a previously published diagonal line in an order/complexity diagram that represents the progression of evolution, it is shown that the GARD model has the potential to advance in this direction. These results can serve as a solid foundation for identifying general criteria for future analyses of evolving systems.

The Mystery of Homochirality on Earth.

Homochirality is an obvious feature of life on Earth. On the other hand, extraterrestrial samples contain largely racemic compounds. The same is true for any common organic synthesis. Therefore, it has been a perplexing puzzle for decades how these racemates could have formed enantiomerically enriched fractions as a basis for the origin of homochiral life forms. Numerous hypotheses have been put forward as to how preferentially homochiral molecules could have formed and accumulated on Earth. In this article, it is shown that homochirality of the abiotic organic pool at the time of formation of the first self-replicating molecules is not necessary and not even probable. It is proposed to abandon the notion of a molecular ensemble and to focus on the level of individual molecules. Although the formation of the first self-replicating, most likely homochiral molecule, is a seemingly improbable event, on a closer look, it is almost inevitable that some homochiral molecules have formed simply on a statistical basis. In this case, the non-selective leap to homochirality would be one of the first steps in chemical evolution directly out of a racemic "ocean". Moreover, most studies focus on the chirality of the primordial monomers with respect to an asymmetric carbon atom. However, any polymer with a minimal size that allows folding to a secondary structure would spontaneously lead to asymmetric higher structures (conformations). Most of the functions of these polymers would be influenced by this inherently asymmetric folding. Furthermore, a concept of physical compartmentalization based on rock nanopores in analogy to nanocavities of digital immunoassays is introduced to suggest that complex cell walls or membranes were also not required for the first steps of chemical evolution. To summarize, simple and universal mechanisms may have led to homochiral self-replicating systems in the context of chemical evolution. A homochiral monomer pool is deemed unnecessary and probably never existed on primordial Earth.

Could Life Have Started on Mars? Planetary Conditions That Assemble and Destroy Protocells.

Early Mars was likely habitable, but could life actually have started there? While cellular life emerged from prebiotic chemistry through a pre-Darwinian selection process relevant to both Earth and Mars, each planet posed unique selection 'hurdles' to this process. We focus on drivers of selection in prebiotic chemistry generic to Earth-like worlds and specific to Mars, such as an iron-rich surface. Iron, calcium, and magnesium cations are abundant in hydrothermal settings on Earth and Mars, a promising environment for an origin of life. We investigated the impact of cations on the stability and disruption of different primitive cell membranes under different pH conditions. The relative destabilizing effect of cations on membranes observed in this study is Ca2+ > Fe2+ > Mg2+. Cation concentrations in Earth systems today are too low to disrupt primitive membranes, but on Mars concentrations could have been elevated enough to disrupt membranes during surface dehydration. Membranes and RNA interact during dehydration-rehydration cycles to mutually stabilize each other in cation-rich solutions, and optimal membrane composition can be 'selected' by environmental factors such as pH and cation concentrations. We introduce an approach that considers how life may have evolved differently under the Martian planetary conditions and selective pressures.

Prolinyl Phosphoramidates of Nucleotides with Increased Reactivity.

Nucleoside monophosphates (NMPs) are the subunits of RNA. They are incorporated into growing complementary strands when sequences are copied in enzyme-free reactions using organic leaving groups at the phosphates. Amino acids are rarely considered as leaving groups, but proline can act as a leaving group when N-linked to NMPs, so that prolinyl NMPs hydrolyze in aqueous buffer at 37 °C, with half-life times as short as 2.4 h, and they act as monomers in enzyme-free primer extension. Still, their level of reactivity is insufficient for practical purposes, requiring months for some extensions. Herein we report the synthesis of eight substituted prolinyl AMPs together with seven related compounds and the results of a study of their reactivity. A δ-carboxy prolinyl NMP was found to be converted with a half-life time of just 11 min in magnesium-free buffer, and a δ-isopropyl prolinyl NMP was shown to react sevenfold faster than its prolinyl counterpart in enzyme-free genetic copying of RNA. Our results indicate that both anchimeric and steric effects can be employed to increase the reactivity of aminoacidyl nucleotides, i.e. compounds that combine two fundamental classes of biomolecules in one functional entity.

Prebiotic Astrochemistry from Astronomical Observations and Laboratory Spectroscopy.

The discovery of more than 200 gas-phase chemical compounds in interstellar space has led to the speculation that this nonterrestrial synthesis may play a role in the origin of life. These identifications were possible because of laboratory spectroscopy, which provides the molecular fingerprints for astronomical observations. Interstellar chemistry produces a wide range of small, organic molecules in dense clouds, such as NH2COCH3, CH3OCH3, CH3COOCH3, and CH2(OH)CHO. Carbon (C) is also carried in the fullerenes C60 and C70, which can preserve C-C bonds from circumstellar environments for future synthesis. Elusive phosphorus has now been found in molecular clouds, the sites of star formation, in the molecules PO and PN. Such clouds can collapse into solar systems, although the chemical/physical processing of the emerging planetary disk is uncertain. The presence of molecule-rich interstellar starting material, as well as the link to planetary bodies such as meteorites and comets, suggests that astrochemical processes set a prebiotic foundation.