Search Results (221)

Stellar irradiation is thought to be a significant contributor to the origin of life. Ultraviolet (UV) light interacting with iron cyanide complexes may play an important role in prebiotic chemistry. The UV–Visible (UV–Vis) spectra of these iron cyanide complexes can be measured by the same source that drives the chemistry, providing a real-time in situ quantitative analysis of prebiotically relevant, UV-driven photochemistry. We measure the UV–Vis absorbances of ferrocyanide and nitroprusside, and relate these absorbances to known concentrations. We show that these absorbances can be combined to accurately predict the concentrations of ferrocyanide–nitroprusside mixtures that could be generated from ferrocyanide and nitroxyl salts irradiated by ultraviolet light. The ferrocyanide molar attenuation coefficients were found to be maximal at the following: ${\epsilon }_{ferrocyanide}\left(340\mathrm{nm}\right)=(2.2\pm 0.4)\times {10}^3{\mathrm{dm}}^2{\mathrm{mol}}^{-1}$. Nitroprusside peaks show the following values: ${\epsilon }_{nitroprusside}\left(340\mathrm{nm}\right)=(4.1\pm 0.3)\times {10}^2{\mathrm{dm}}^2{\mathrm{mol}}^{-1}$, ${\epsilon }_{nitroprusside}\left(400\mathrm{nm}\right)=(1.71\pm 0.05)\times {10}^2{\mathrm{dm}}^2{\mathrm{mol}}^{-1}$, and ${\epsilon }_{nitroprusside}\left(500\mathrm{nm}\right)=62.1\pm 1.7{\mathrm{dm}}^2{\mathrm{mol}}^{-1}$. With the help of our measured absorbances, we consider ferrocyanide and nitroprusside to function as sunscreens. In the absence of continuous ferrocyanide sources, UV-sensitive compounds could be protected on timescales of months. This would allow for compounds like nicotinamide adenine dinucleotide, NADH, to survive for over a year at depths of 5 m, compared to a lifetime of 6 months when unprotected. Our toy model constrains the photochemical survival of compounds of interest to the origin of life community across a comprehensive spectral range and can be used to constrain the survival using different exoplanetary irradiative conditions; thus, we are able to explore the UV environment with the presence of ferrocyanide and nitroprusside and contribute to the wider discussion surrounding the prevalence of the origin of life in the Universe. Full article

This work develops a geometric and statistical framework for analyzing the structure of biological sequences and explores its implications for understanding the emergence and evolution of life. Motivated by questions concerning the transition from prebiotic chemistry to living systems, the quantification of negentropy in organic matter, and the distinction between random and biologically viable sequences, we introduce mathematical descriptors that measure deviation from linearity and related geometric irregularities of self-replicating macromolecules. These descriptors reveal a pronounced geometric separation between biological DNA and random sequences, underscoring the non-random structural organization characteristic of living systems. Using these descriptors, we compare a broad range of species across the Tree of Life and examine how geometric complexity varies between primitive and more advanced organisms. We further investigate whether these measures provide a natural way to compare organismal complexity, characterize the structure of viable sequence space, and identify potential constraints on evolutionary trajectories. The framework also offers an initial perspective on how natural selection and stochastic mutations may jointly influence genomic organization. Finally, we outline speculative connections between increasing geometric irregularity and the emergence of biological complexity, suggesting that such geometric transitions may offer insight into the origins of life and the theoretical limits of evolutionary development. Full article

The RNA-World hypothesis remains the most widely accepted framework in origins-of-life research, anchored in compelling biochemical evidence for RNA’s deep evolutionary ancestry. However, this viewpoint routinely extends beyond that and is frequently conflated with claims that RNA served as life’s primal substrate. This essay argues that the RNA-First paradigm, in its pursuit of this claim, systematically projects biological biases onto a chaotic and combinatorially vast abiotic landscape. It relies on privileged, highly complex molecular constructs whose spontaneous emergence in such combinatorial settings is overwhelmingly implausible. Critically, the experimental evidence accumulated in support of RNA-First has largely demonstrated the compatibility of RNA with prebiotic conditions, but not its probability, necessity, or chemical precedence over the numerous alternatives that abiotic chemistry affords. The eventual emergence of RNA chemistry demands a preceding protobiological stage, characterized by chemically diverse, collectively autocatalytic molecular networks. Embracing this broader protobiological framework, and confronting the true combinatorial complexity of abiotic chemistry, is essential for a rigorous and unbiased account of life’s origin. Full article

The emergence of membrane boundaries represents a decisive transition in the origin of life, yet the molecular nature of the earliest abiotic membranes remains uncertain. Existing models based on simple fatty acids, while experimentally tractable, often lack the environmental robustness required under fluctuating prebiotic conditions. Furthermore, the absence of clear pathways linking primitive amphiphiles to later phospholipid systems highlights the need for chemically continuous intermediate frameworks. Here, we explore borate-bridged amphiphile–carbohydrate conjugates as plausible intermediates between simple prebiotic surfactants and modern lipid bilayers. These conjugates arise from low-molecular-weight polyols—including glycerol, butane-1,2,3,4-tetraol, pentane-1,2,3,4,5-pentaol, and hexane-1,2,3,4,5,6-hexitol—reacting with long-chain alkyl ethers and borate species under alkaline conditions, enabling reversible coupling to ribose and other vicinal diol-containing sugars. This chemistry integrates three essential properties for early compartmentalization: hydrolytically robust ether-linked hydrophobic domains, multivalent and highly hydrated headgroups, and environmentally responsive borate coordination. Comparative physicochemical analysis suggests that single-tail alkylglycerol derivatives preferentially form micelles and interfacial films, while di- and tri-tail tetritol and pentitol conjugates favor lamellar assemblies and vesicle formation across realistic prebiotic pH and salinity ranges. Hexitol-based systems, particularly those bearing three hydrophobic chains, may act as membrane-stabilizing components that enhance rigidity and reduce permeability under extreme conditions. We propose that heterogeneous mixtures dominated by two-tail polyol diethers, supplemented by tri-tail stabilizers and surface-active alkylglycerols, could provide mechanically robust, pH-tunable, and sugar-decorated abiotic membranes. Such borate-mediated amphiphiles offer a chemically coherent framework linking carbohydrate stabilization, ether lipid persistence, and dynamic self-assembly, potentially representing a transitional stage in the evolutionary pathway from primitive amphiphilic films to biologically encoded membranes. Full article

The origin of life is commonly discussed within two competing conceptual frameworks: the metabolism-first and information-first hypotheses. While each emphasizes a different defining property of early life, modern biochemistry reveals a fundamental interdependence between metabolic processes and genetic information transfer, leading to a persistent chicken-and-egg problem. In this study, we investigate a prebiotically plausible reaction system that enables the concurrent formation of molecular precursors associated with both frameworks. Under simulated Hadean hydrothermal conditions, acetylene, ammonia, cyanide, and carbon monoxide were reacted in aqueous solution in the presence of transition metal sulfides. Using gas chromatography–mass spectrometry combined with stable isotope labeling, we demonstrate the simultaneous formation of the nucleobase uracil and the amino acids alanine and aspartic acid. Isotopic incorporation patterns allow reconstruction of the underlying reaction pathways and confirm the contribution of all starting materials to product formation. While amino acids are produced continuously over the observed period in significantly higher yields than uracil, uracil formation exhibits a pronounced time-dependent maximum after three days. Variations in pH, reaction time, and metal sulfide catalysts modulate product yields but do not prevent the parallel emergence of both molecular classes. These findings support a scenario in which proto-metabolic chemistry and molecular precursors of genetic information could have arisen simultaneously within a shared geochemical setting. The results provide experimental support for a coupled origin of metabolism and transcriptional building blocks, offering a potential resolution to the dichotomy between metabolism-first and information-first models of early life. Full article

This study examines the influence of SO₂ and its hydrate H₂SO₃ on the free energies of the core autocatalytic cycle of the formose reaction. We find that SO₂ and H₂SO₃ readily condense with aldehyde and alcohol functional groups to form bisulfite analogs of formose proto-metabolites under modeled conditions. The bisulfite functional group can provide intramolecular catalytic enhancement in specific isomers towards aldol additions and the retroaldol step that regenerates two equivalents of glycolaldehyde from tetrose. The bisulfite moiety reduces the favorability of the parasitic Cannizzaro side-reaction both thermodynamically and kinetically, thus potentially furnishing more throughput towards forming sugars. As a prebiotic analog to phosphate, we find that bisulfite slightly stabilizes ribose over its C₅ aldose diastereomers thermodynamically, although the effect is modest and may be influenced by solution dynamics. Full article

The origin of life is, to the best of our knowledge, impossible to imagine without the formation of complex prebiotic biomolecules such as RNA, DNA, proteins and lipids. Lipids play a crucial role in the spontaneous formation of cell membranes, which are responsible for cell integrity, compartmentalization, selective permeability, and providing a microenvironment for biochemical reactions. The goal of the current work is to summarize the current state of the art regarding the abiotic formation of membrane building blocks, such as glycerol, fatty acids, and their phosphorylated version as phospholipid precursors. We describe the necessity of a systems chemistry approach for the complexification and expansion of the prebiotic network, enabling the formation of several membranogenic precursors. We also discuss prebiotic pathways for phosphorylation and acylation that could lead to phospholipid availability in hydrothermal environments and on the early Earth surface. We conclude with the possible spontaneous vesiculation of these molecules as a primitive version of the cell membrane. Thus, we present a comprehensive perspective on prebiotic vesicle formation, starting from simple molecules and developing until the self-assembly of vesicles. Full article

Liquid is a fundamental requirement for life as we understand it, but whether that liquid has to be water is not known. We propose the hypothesis that ionic liquids (ILs) and deep eutectic solvents (DES) constitute a class of non-aqueous planetary liquids capable of persisting on a wide range of bodies where stable liquid water cannot exist. This hypothesis is motivated by key physical properties of ILs and DES. Many exhibit vapor pressures orders of magnitude lower than that of water and remain liquid across exceptionally wide temperature ranges, from cryogenic to well above terrestrial temperatures. These properties permit stable liquids to exist where liquid water would rapidly evaporate or freeze and outside of bulk phases as persistent microscale reservoirs—such as thin films and pore-filling droplets. In other words, ILs and DES can persist in environments without requiring oceans, thick atmospheres, or narrowly regulated climate conditions. We further hypothesize that ILs and DES could act as solvents for non-Earth-like life, based on their polar nature and the demonstrated stability and functionality of proteins and other biomolecules in ionic liquids. More speculatively, our hypothesis extends to the idea that ILs and DES could enable prebiotic chemistry by providing long-lived, protective liquid environments for complex organic molecules on bodies such as comets and asteroids, where liquid water is absent. Additionally, based on the occurrence of DES-like mixtures as protective intracellular liquids in desiccation-tolerant plants, we propose that ILs and DES might be solvents that life elsewhere purposefully evolves. We review protein and other biomolecule studies in ILs and DES and outline planetary environments in which ILs and DES might occur by discussing available anions and cations. We present strategies to advance the IL/DES solvent hypothesis using laboratory studies, computational chemistry, planetary missions, analysis of existing spectroscopic datasets, and modeling of liquid microniches and chemical survival on small bodies. Full article

The spontaneous emergence of macroscopic dissipative structures in systems driven by generalized chemical potentials is well established in non-equilibrium thermodynamics. Examples include atmospheric/oceanic currents, hurricanes and tornadoes, Rayleigh–Bénard convection cells and reaction–diffusion patterns. Less well recognized, however, are microscopic dissipative structures that form when the driving potential excites internal molecular degrees of freedom (electronic states and nuclear coordinates), typically via high-energy photons or coupling with ATP. Examples include dynamic nanoscale lipid rafts, kinesin or dynein motors along microtubules, and spatiotemporal Ca²⁺ signaling waves propagating through the cytoplasm. The thermodynamic dissipation theory of the origin of life asserts that the core biomolecules of all three domains of life originated as self-organized molecular dissipative structures—chromophores or pigments—that proliferated on the Archean ocean surface to absorb and dissipate the intense “soft” UV-C (205–280 nm) and UV-B (280–315 nm) solar flux into heat. Thermodynamic coupling to ancillary antenna and surface-anchoring molecules subsequently increased photon dissipation and enabled more complex dissipative processes, including photosynthesis, to dissipate lower-energy but higher-intensity UV-A and visible light. Further thermodynamic coupling to abiotic geophysical cycles (e.g., the water cycle, winds, and ocean currents) ultimately led to today’s biosphere, efficiently dissipating the incident solar spectrum well into the infrared. This paper reviews historical considerations of UV light in life’s origin and our proposal of UV-C molecular dissipative structuring of three classes of fundamental biomolecules: nucleobases, fatty acids, and pigments. Increases in structural complexity and assembly into larger complexes are shown to be driven by the thermodynamic imperative of enhancing solar photon dissipation. We conclude that thermodynamic selection of dissipative structures, rather than Darwinian natural selection, is the fundamental creative force in biology at all levels of hierarchy. Full article

Post-cholecystectomy non-alcoholic fatty liver disease (NAFLD), now encompassed within metabolic dysfunction-associated steatotic liver disease (MASLD), is increasingly linked to persistent disruption of bile acid kinetics and gut–liver axis signaling after gallbladder removal. Continuous bile delivery to the intestine reshapes the bile acid pool, perturbs FXR–FGF19/TGR5 pathways, remodels gut microbiota, and compromises epithelial barrier integrity, collectively promoting portal endotoxemia, chronic hepatic inflammation, and fibrogenic remodeling. Hydrogel-based biomaterials offer a mechanistically aligned therapeutic platform for this setting because they enable localized, sustained, and stimuli-responsive interventions at intestinal or hepatic sites. Functional hydrogels can sequester excess bile acids, protect and deliver probiotics/prebiotics/postbiotics, reinforce mucosal barrier function, and provide controlled release of anti-inflammatory or antifibrotic agents with reduced systemic exposure. In this review, we map emerging hydrogel strategies relevant to post-cholecystectomy NAFLD across four pathogenic nodes, bile acid dysregulation, dysbiosis, inflammation, and fibrosis, and highlight design principles (polymer chemistry, charge/hydrophobicity balance, mucoadhesion, and pH/redox/enzyme responsiveness) that enable targeted modulation of the gut–liver axis. Finally, we identify key translational gaps, including the lack of post-cholecystectomy-specific experimental models and standardized outcome measures integrating bile acid profiling, microbiome readouts, and hepatic histology. Hydrogel technologies represent a promising route toward localized and multimodal therapy in metabolic liver disease, warranting focused preclinical validation and clinical development. Full article

Traditional prebiotic chemistry experiments often isolated single reactions under clean, controlled conditions, yet early Earth was chemically diverse and physically dynamic. Such primordial complexity likely imposed obstacles, including side reactions, low yields, and unstable intermediates, but it also generated opportunities, including redundant routes, parallel pathways, and environmental filters that could bias mixtures toward subsets of persistent and chemically productive compounds. This review examines how heterogeneous prebiotic settings could generate RNA precursors, including nucleobases, ribose, and phosphate-containing species, through multiple concurrent pathways. Although side reactions can sequester carbon in inert tars and reduce yields of specific targets, networked chemistry can also enhance robustness when different routes converge on shared intermediates, or when apparent byproducts reenter productive cycles. Environmental factors such as ultraviolet irradiation, mineral surfaces, wet-dry cycling, and thermal gradients can act as constraints that enrich certain products by differential stability, reactivity, and compartmentalization. In this context, the RNA world hypothesis remains compelling, as RNA can store heritable sequence information and catalyze reactions through sequence dependent folding, thereby linking heredity and chemistry within a single polymer. At the same time, the emergence of functional sequence information and of control architectures that couple sequence to reproducible function remains a central open problem, and it sets clear limits on what chemistry alone can explain. Rather than dismissing messy mixtures as irrelevant noise, it is more accurate to treat them as the native context in which concentration mechanisms, environmental cycling, and selective persistence could enable the accumulation and survival of RNA related molecules. Full article

Chemical complexity is not a nuisance to be minimized in origin of life research, it is an enabling condition. This second edition of the Special Issue on the Origin of Life in Chemically Complex Messy Environments gathers contributions that embrace multicomponent mixtures, dynamic geochemical settings, and nonequilibrium processes. The papers collected here survey surface hydrothermal routes to reactive nitriles, groundwater evolution of alkaline lakes, and transition metal sulfide-driven amino acid and amide formation without cyanide. They report one pot nucleoside and nucleotide synthesis from formamide over cerium phosphate, review non aqueous organophosphorus pathways, and probe peptide rich mixtures and formose type networks under serpentinization associated minerals. The issue also advances conceptual frameworks, including atmospheric photochemical signatures for biosignature discrimination, the role of chiral mineral surfaces in enantioseparation, and computational simulations of the origin of LUCA. Together, these studies position messy chemistry as a crucible that turns chemical diversity and environmental heterogeneity into routes toward organization and function. Full article

The origin of life embodies two fundamental questions: how and when did life begin? It is commonly conjectured that life began on Earth around 4 billion years ago. This requires that the complex organization of RNA, DNA, triplet codon, protein, and lipid membrane (RDTPM) architecture was easy to establish between the time the Earth cooled enough for liquid water and the time when early microorganisms appeared. These bracketing events create a narrow window of time to construct a completely operational self-replicating organic system of very high complexity. Another conjecture is that life did not begin on Earth but was seeded from life-bearing space objects (e.g., asteroids, comets, space dust), commonly referred to as panspermia. The second conjecture implies that life formed somewhere else and was part of the solar nebula, originating from an earlier generation star where there was more time available for the development of life. In this paper, the goal is to provide a hypothetical perspective related to the timing for the origin of pre-biotic chemistry and life itself. Using a form of complexity growth, biological features spanning from the present day back to early life on Earth were examined for trends across time. Genome sizes, gene number, protein–protein binding sites, energy for cell construction, mass of individual cells, the rate of cell mass growth, and a molecular complexity measure all yield highly significant regressions of linearly increasing complexity when plotted over the last 4 Gyr (billion years). When extrapolated back in time, intersections with simple complexities associated with each variable yield a mean value of 8.6 Gyr before the present time. This era coincides with the peak of star and planet formation in the universe. This speculative analysis is consistent with the second conjecture for the origin of life. The major assumptions of such an analysis are presented and discussed. Full article

There is an urgent need to evaluate the toxicity of xenobiotics and environmental mixtures for preventing loss in water quality for the sustainability of aquatic ecosystems. A simple prebiotic chemical pathway based on malate formation from pyruvate (pyr) and glyoxalate (glyox) is proposed as a quick and cheap screening tool for toxicity assessment. The assay is based on the pyr and glyox (aldol) condensation reactions, leading to biologically relevant precursors such as oxaloacetate and malate. Incubation of pyr and glyox at 40–70 °C in the presence of reduced iron Fe(II) led to malate formation following the first 3 h of incubation. The addition of various xenobiotics/contaminants (silver, copper, zinc, cerium IV, samarium III, dibutylphthalate, 1,3-diphenylguanidine, carbon-walled nanotube, nanoFe₂O₃ and polystyrene nanoparticles) led to inhibitions in malate synthesis at various degrees. Based on the concentration inhibiting malate concentrations by 20% (IC20), the following potencies were observed: silver < copper ~ 1.3-diphenylguanidine ~ carbon-walled nanotube < zinc ~ samarium < dibutylphthalate ~ samarium < Ce(IV) < nFeO₃ < polystyrene nanoplastics. The IC20 values were also significantly correlated with the reported trout acute lethality data, suggesting its potential as an alternative toxicity test. The pyr-glyox pathway was also tested on surface water extracts (C18), identifying the most contaminated sites from large cities and municipal wastewater effluents dispersion plume. The inhibition potencies of the selected test compounds revealed that not only pro-oxidants but also chemicals hindering enolate formation, nucleophilic attack of carbonyls and dehydration involved in aldol-condensation reactions were associated with toxicity. The pyr-glyox pathway is based on prebiotic chemical reactions during the emergence of life and represents a unique tool for identifying toxic compounds individually and in complex mixtures. Full article

Agri-food residues have accumulated globally at unprecedented scales, generating environmental pressures and resource inefficiencies, a core problem addressed in this review, while simultaneously representing rich, underutilized reservoirs of health-promoting phytochemicals. This review synthesizes recent advances (2016–2025) in the green extraction, characterization, and biological validation of phytochemicals from plant-based residues, including polyphenols, flavonoids, carotenoids, alkaloids, and dietary fibers from key sources such as grape pomace, citrus peels, coffee silverskin, pomegranate peel, cereal brans, and tropical fruit by-products. Emphasis is placed on sustainable extraction methods: ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), pressurized liquid extraction (PLE), supercritical CO₂ extraction (SFE), and natural deep eutectic solvents (NADES), which enable efficient recovery while minimizing environmental impact. In vitro, in vivo, and clinical studies demonstrate that residue-derived compounds exert antioxidant, anti-inflammatory, metabolic-regulating, and prebiotic effects, contributing to health in general and gut microbiota modulation. Integrating these bioactives into functional foods and nutraceuticals supports sustainable nutrition and circular bioeconomy goals by reducing food waste and promoting health-oriented valorization. Regulatory advances, including approvals from the European Food Safety Authority (EFSA) and the U.S. Food and Drug Administration (FDA) for ingredients such as olive phenolics, citrus flavanones, and coffee cascara, further illustrate increasing translational readiness. The convergence of green chemistry, biorefinery design, and nutritional science positions agri-food residues as pivotal resources for future health-promoting and environmentally responsible diets. Remaining challenges include scaling cost-effective green processes, harmonizing life cycle assessment protocols, expanding toxicological datasets, and conducting longer-term clinical trials to support safe and evidence-based commercialization. Full article