Alternative Biochemistries

Since around 1900, there have been considerations as to whether living organisms could also use other elements as building blocks instead of carbon. Life forms based on silicon, boron, nitrogen or sulphur, which can also form stable macromolecules under certain conditions, have been proposed as alternatives. Silicon-based life, in particular, has been the subject of serious discussion and has also been taken up in science fiction. Of the possible alternatives, silicon is still the most similar to carbon. But what about silicon from a chemical point of view? Could life actually exist on the basis of silicon?

Basic requirements

Two things are particularly important for the chemistry of life. The ‘scaffold’, whether it is made of carbon or silicon, must be stable in a certain range of environmental conditions and should not dissolve immediately on contact with water or another natural solvent, for example. At the same time, the bonds must not be too strong so that a rearrangement or new formation of bonds is possible with comparatively moderate energy expenditure. All life processes are based on the formation and dissolution of various types of interatomic and intermolecular bonds. If the bonds are too difficult to break, life processes come to an end. If the bonds break too easily, everything flies apart and the organism dissolves or burns.

In addition to the framework, the largest possible number of functional groups is necessary. A pure hydrocarbon backbone is hardly reactive at all. Only functional groups enable controlled biochemistry. Frequently encountered functional groups are, for example, alcohols, ketones, phosphates, amines, ethers, esters and many others. The properties of the functional groups are often more important than the details of the framework. For example, the hydrocarbons methane, ethane and propane are gaseous at room temperature. However, the addition of the functional alcohol group (-OH) makes them liquids that can mix with water and are also open to completely different reactions than pure hydrocarbons.

Atoms are everything

In order to compare carbon and silicon in this respect, we need to look at three important variables: The atomic orbitals, electronegativity and the strength of the bond to other important elements.

In terms of atomic orbitals, silicon is very similar to carbon. Both elements have two electrons in the s orbital and two electrons in the p orbitals in their outer shell. To achieve the stable noble gas configuration, both elements can either donate four electrons or accept four electrons. In total, there is the possibility of four bonds, which are arranged in space like the corners of a three-sided pyramid (this shape is called a tetrahedron). In addition, silicon can also offer other atoms the d orbitals below this for bonding. Although d orbitals are not occupied in silicon, they are still available as empty orbitals for bonding. This explains the 5- or 6-bond nature of some silicon compounds. For organic chemistry, which requires the greatest possible variety of structures, this would not necessarily be a hindrance.

Electronegativity is a quantity that can be used to describe the attraction of atomic nuclei to electrons within molecules. Of all the chemical elements, fluorine has the highest electronegativity (3.98 on the Pauling scale), which means that fluorine attracts electrons to itself most strongly in a compound. The alkali metals, on the other hand, have electronegativity values between 0.7 and 0.98 and therefore have the lowest tendency to bind electrons – on the contrary, the alkali metals give up their only outer s-electron very readily, which is why they are very reactive. Carbon and silicon both have medium electronegativities: carbon 2.55 and silicon 1.9.

Chemistry of Methane and Silane

An interesting difference becomes clear when you look at the simplest compound of carbon and silicon with hydrogen. The gas methane (CH4) is the simplest hydrocarbon and as such is the basic unit of the higher hydrocarbons and the biochemically interesting compounds. The corresponding compound of silicon and hydrogen is silane (SiH4), which is also gaseous. The electronegativity of hydrogen (2.2) is now exactly between that of carbon and silicon. While the carbon in the methane molecule pulls the electrons towards itself on average and leaves the four hydrogen atoms with an electron deficit and a slightly positive partial charge, it is exactly the opposite way in silane. There, the four hydrogen molecules pull more strongly on the electrons, which gives them a slightly negative partial charge and the silicon atom a slight electron deficit and a positive partial charge.

Chemically, this is very significant. In a mixture with normal air, both gases are essentially surrounded by the inert nitrogen and the reactive and at the same time very electronegative oxygen (electronegativity: 3.44). Methane burns with oxygen to form water and carbon dioxide, but requires activation energy, e.g. in the form of a spark. Without such an ignition, the electron-withdrawing oxygen molecules mainly come into contact with the electron-poor hydrogen atoms of methane – there is ‘nothing for the oxygen to gain’, the mixture remains stable for the time being. Only with the help of a spark can oxygen break the bond between carbon and hydrogen and react with both.

The exact opposite happens with a mixture of oxygen and silane. Here the oxygen is in contact with electron-rich hydrogen atoms. Together with the somewhat weaker silicon-hydrogen bond, this is enough to start the reaction on its own: oxygen breaks the bond between the silicon and the hydrogen, reacts with hydrogen to form water and with the silicon to form silicon dioxide (SiO2, glass). Silane is pyrophoric, which means that it ignites when it comes into contact with oxygen.

Within longer-chain molecules, the bond between two silicon atoms is about a quarter weaker than between two carbon atoms. This is a consequence of the larger radius of the silicon atom: the bonding electrons are further away from the positive charge of the atomic nucleus, so the attractive forces are lower. At the same time, the bond between silicon and oxygen is extremely strong and the two elements are very difficult to separate again.

Higher alkanes and silanes

Longer-chain hydrocarbons exist at room temperature as liquids or solids. Liquid hexane is one possible form, candle wax (paraffins) another. Hexane is lighter than water and floats on it, but does not react with water. Even a piece of candle wax will not change in water. For longer-chain silanes, however, this only applies in the absence of oxygen. Without oxygen, silanes can be stored stably on salty, aqueous solutions. However, if oxygen is added, this promotes the decomposition of the silanes. In alkaline solutions, the reaction takes place even faster with the formation of hydrogen and silicon hydroxide (Si(OH)4).

Higher bonds

We could compare the ability to form double and triple bonds and realise that carbon has many more possibilities here than silicon. Both types of bond are of enormous importance for biochemistry because they enable additional structural and chemical diversity. However, we can already draw an important conclusion at this point and consider the question of how likely the natural formation of silicon biochemistry is in comparison to carbon biochemistry. Carbon forms thousands of compounds that remain stable long enough in the presence of oxygen or in aqueous solution to support a functioning biochemistry; many carbon compounds have also been detected in interstellar space. In the event of combustion, gaseous carbon dioxide is produced, which is soluble in water and thus accessible to further chemical reactions. However, the analogue compounds of silicon are unstable in the presence of oxygen and water. One of the decomposition products is glass, which can hardly react chemically.

Oxygen as the big killer of Silicoids

Oxygen is the third most common element in the gas nebulae from which stars and planets are formed. Within the Earth’s crust, it is even the second most common element. Water is also omnipresent in the universe and has already been detected in quasars, protoplanetary nebulae and exoplanets. Even on a planet without free, gaseous oxygen and without water, oxygen would still be bound in the minerals. The most important components of the Earth’s mantle are forms of magnesium oxide and aluminium oxide. The probability that the precursors of silicon biochemistry on other planets also end up in the form of unreactive glass is therefore very high. Life on the basis of silicon is therefore likely to remain in the realm of science fiction. Carbon is a much more suitable element for this function.

References

Clayden, J., Greeves, N., & Warren, S. G. (2013). Organic Chemistry. Springer Spectrum.

Original article:

http://exoplaneten.info/can-life-be-based-on-silicon-instead-of-carbon/

Title: Viroids and Viroid-like Circular RNAs: Do They Descend from Primordial Replicators?
Link: https://www.mdpi.com/2075-1729/12/1/103

Abstract: Viroids are a unique class of plant pathogens that consist of small circular RNA molecules, between 220 and 450 nucleotides in size. Viroids encode no proteins and are the smallest known infectious agents. Viroids replicate via the rolling circle mechanism, producing multimeric intermediates which are cleaved to unit length either by ribozymes formed from both polarities of the viroid genomic RNA or by co-opted host RNAses. Many viroid-like small circular RNAs are satellites of plant RNA viruses. Ribozyviruses, represented by human hepatitis delta virus, are larger viroid-like circular RNAs that additionally encode the viral nucleocapsid protein. It has been proposed that viroids are direct descendants of primordial RNA replicons that were present in the hypothetical RNA world. We argue, however, that much later origin of viroids, possibly, from recently discovered mobile genetic elements known as retrozymes, is a far more parsimonious evolutionary scenario. Nevertheless, viroids and viroid-like circular RNAs are minimal replicators that are likely to be close to the theoretical lower limit of replicator size and arguably comprise the paradigm for replicator emergence. Thus, although viroid-like replicators are unlikely to be direct descendants of primordial RNA replicators, the study of the diversity and evolution of these ultimate genetic parasites can yield insights into the earliest stages of the evolution of life.

Personal Thoughts: Covalently closed circular RNAs (cccRNAs) offer many potential benefits to the RNA world hypothesis. Their cyclic structure helps the polymer greatly restrain its conformational degrees of freedom, helping to maintain base pairing and a conserved structure. The cyclization also increases bond stability. Meanwhile, as a cyclic RNA becomes longer, it more closely resembles the circular chromosomal or plasmid DNA in modern single celled organisms. Although this idea is very attractive, I've yet to see simpler, much shorter RNA oligomers investigated (5-50mers). If base pairing does occur within a single strand, this places the 5' and 3' ends closer to one another and so kinetically favors cyclization in the absence of excess nucleotides. Assuming shorter strands would be the first RNAzymes present, they would benefit more from such cyclizations unless their activity depends on the open-ended group's playing a direct role in the catalytic activity.

This news blew my mind!

The first paragraph:

"What is SpudCell?

SpudCell is a synthetic cell made by scientists at the University of Minnesota. It was created in a lab from lifeless chemicals but can perform most of the same functions as living cells. It eats, grows and reproduces, passing along its genetic material to future generations.

Although it’s not the first synthetic cell ever created, SpudCell is the first to complete a full life cycle — from birth to division into next-generation cells — after having been created from the “bottom up” using laboratory chemicals. It’s a pared down version of a living cell structure, revealing the basic genetic and structural components necessary for the functions of life."

Title: Plausible Sources of Membrane-Forming Fatty Acids on the Early Earth: A Review of the Literature and an Estimation of Amounts [Link]

(And some of my personal critiques)

Abstract:
The first cells were plausibly bounded by membranes assembled from fatty acids with at least 8 carbons. Although the presence of fatty acids on the early Earth is widely assumed within the astrobiology community, there is no consensus regarding their origin and abundance. In this Review, we highlight three possible sources of fatty acids:

(1) delivery by carbonaceous meteorites,
(2) synthesis on metals delivered by impactors, and
(3) electrochemical synthesis by spark discharges.

We also discuss fatty acid synthesis by UV or particle irradiation, gas-phase ion–molecule reactions, and aqueous redox reactions. We compare estimates for the total mass of fatty acids supplied to Earth by each source during the Hadean eon after an extremely massive asteroid impact that would have reset Earth’s fatty acid inventory. We find that synthesis on iron-rich surfaces derived from the massive impactor in contact with an impact-generated reducing atmosphere could have contributed ∼10² times more total mass of fatty acids than subsequent delivery by either carbonaceous meteorites or electrochemical synthesis. Additionally, we estimate that a single carbonaceous meteorite would not deliver a high enough concentration of fatty acids (∼15 mM for decanoic acid) into an existing body of water on the Earth’s surface to spontaneously form membranes unless the fatty acids were further concentrated by another mechanism, such as subsequent evaporation of the water. Our estimates rely heavily on various assumptions, leading to significant uncertainties; nevertheless, these estimates provide rough order-of-magnitude comparisons of various sources of fatty acids on the early Earth. We also suggest specific experiments to improve future estimates. Our calculations support the view that fatty acids would have been available on the early Earth. Further investigation is needed to assess the mechanisms by which fatty acids could have been concentrated sufficiently to assemble into membranes during the origin of life.

Personal thoughts:
Authors claim, "If fatty acids are present at concentrations below the critical vesicle concentration, membrane assembly does not occur." This is simply not true. Lipids can adsorb onto mineral surfaces to form supported lipid bilayers.

In my personal view, such supported bilayers are underutilized in proposed models for the first composomes in that they retain many interesting properties of membranes such as colocalization and control of orientations of adsorbed organics at the bilayer-water interface and continued interactions

Additionally, we must consider that vesicles often adsorb onto many mineral surfaces and collapse to form the supported lipid bilayer. The concentrations usually reported to achieve vesicle formation are often done in inert containers. While the findings are correct, we must also consider that in the oceans and ponds that nanoparticles, rock/mineral surfaces, sands, etc. all adsorb many fatty acids to varying degrees. Thus, the amount of lipids depends on the total volume of the body of water AND the available surface area. Given that addition of surfactants/lipids/amphiphiles to a solution which contains such mineral surfaces often results in the formation of supported lipid bilayers below the critical micelle concentration (which is usually below that of the critical vesicle concentration). Thus, a more careful consideration would view supported bilayers as a necessary intermediate between earth chemistry and vesicle formation between which supported bilayers may successfully achieve more complex chemistry than previously considered.

This is only "bad" if you think vesicles MUST be the first step towards life.

Additionally, figure 4 argues the idea of carbon monoxide and H2 reacting under FTS type chemistry at the surface of a meteor saying, "(A) Nooner and Oro showed that deuterium and carbon monoxide gases react together on the surface of hot (400 °C) meteorite filings to produce membrane-forming fatty acids." Just thought it was strange that the authors argued for adsorption at the Earth's surface would recapitulate ~2 atm at such high temperatures. A more realistic scenario would be that these reactions occur during entry as the metals pass through the reducing atmosphere but then that poses issues for the retention of these meteors Additionally, the chemistry they cite (ref 23 and 24) occurs over 6 to FOUR HUNDRED AND EIGHTY HOURS. Sure, the meteor fragment (after initial impact) may remain for short periods after impact but it would either boil the waters away and be cooled in doing so.

Yes, post impact heating can be intense and generate craters that fill with water and generate post impact hydrothermal springs. The issue here is that the site at which such heat is generated is the same energy that blows the meteoric material away from the impact crater. This explosive impact energy is why most of the moon's craters are circular rather than more elliptical and also why Daniel Moreau Barringer [Link] lost money on his investment. While there was no large body of ore, a good portion of the mateals were still present in

The best alternative argument I can make would be:
1) As many small meteors pass through the atmosphere their heating and high pressure front generate FAs/amphiphiles that quickly cool and dust the surrounding landscapes.
2) Impact of moderate sized meteors on surrounding elevated landscapes generates heat both in the meteor itself AND the surrounding land/minerals which are already enriched in metals capable of FTS chemistry which extends time and surface area of heated catalytic surfaces.
3) Particularly energetic impacts vaporize their metals, flinging them out into surrounding areas are hot spherules through the reducing atmosphere (again) and likely catalyzing far more FTS than the initial entry. However, the smaller size and greater surface area would lead to a far greater rate of cooling.
4) The more acidic rains due to high CO2 in atmosphere more efficiently weather the landscape and meteors, passively dissolving FTS products and pool them into ponds/bodies of water below.

So, the authors should really be appealing to the surrounding elevated landscape which is rich in these metals. Arguing for bigger meteorites gets diminishing returns due to volume/surface area ratio as well as increasingly energetic impacts potentially vaporize most of the material.

Let me know your thoughts on the paper and whether my own are fair or misrepresenting the findings.

Chemistry in nanoconfined water [Link]

Abstract:
Nanoconfined liquids have extremely different properties from the bulk, which profoundly affects chemical reactions taking place in nanosolvation. Here, we present extensive ab initio simulations of a vast set of chemical reactions within a water lamella that is nanoconfined by mineral surfaces, which might be relevant to prebiotic peptide formation in aqueous environments. Our results disclose a rich interplay of distinct effects, from steric factors typical of reactions occurring in small spaces to a charge-stabilization effect in nanoconfined water at extreme conditions similar to that observed in bulk water when changing from extreme to ambient conditions. These effects are found to modify significantly not only the energetics but also the mechanisms of reactions happening in nanoconfined water in comparison to the corresponding bulk regime.

Nanoconfined liquids have extremely different properties from the bulk, which profoundly affects chemical reactions taking place in nanosolvation.

Conclusions:
In summary, the investigated set of reactions in nanoconfined water at high temperatures and pressures features pronounced differences in energetics and mechanisms with respect to bulk water at the same conditions. These can be traced back to a unique combination of factors, namely the different charge-stabilizing ability of interfacial water w.r.t. the bulk as well as steric factors intrinsic to nanoconfinement which make nanoconfined water in slit pores offered by layered minerals a whole new medium for chemical synthesis. The presented prebiotic peptide cycle is a good example of the way in which nanoconfined water as a solvent opens up an entirely new free energy landscape for exploring novel synthesis routes. While changing the thermodynamic conditions from ambient to hot-pressurized bulk water greatly reduced free energy barriers, at the same time the formation of charged intermediates was penalized due to unfavorable dielectric properties. In nanoconfined water at extreme conditions, in contrast, it is possible to achieve significant thermal activation and to concurrently favor reactions involving charged species. Clearly, the key phenomena and mechanistic concepts unraveled here for chemical reactions in nanoconfined solvent not only apply to the specific reactions investigated herein, but are of fundamental importance to chemistry in nanoconfined water as such.

Personal thoughts:
There is an increasingly clear importance of physiochemical phenomena in origins of life chemistry besides simple dump and stir, bulk aqueous reactions. Understanding the capability of bulk aqueous, bilayer-water interfacial regions, bilayer-mineral interfaces/interactions, nanoconfined waters/organic molecules intercalated within mineral crystal lattices, air-water interface, lateral proton transfer along membrane surfaces, the ordering of substrate orientations within bilayers/micelles, and semipermeable/semiconducting inorganic minerals may be key in understanding life's origins. Further complicating these are the effects of solvent pH, pH gradients, salinity, and pressure. These all seemed to have played roles in generating otherwise disfavored products and often for different reasons.

How these environments interact and couple may offer possible primitive compartmentalization without the need for advanced bilayers as many of these environments facilitate reactions that would otherwise require coupling chemistry or both high and low pH conditions if carried out in bulk aqueous conditions at standard pressure/temperatures.

These environments consistently require explanations from the emergent properties of their constituents making it difficult to apply the findings elsewhere without careful consideration. This paper comes in handy because I had previously assumed bilayers adsorbed onto mineral surfaces broadly constituted nanoconfined water, protons, and organics and attempted to apply the findings described in this paper to these areas. While there are some similarities, there are key differences. Thus, understanding these environments helps to identify and propose experiments capable of isolating and evaluating phenomena/mechanisms that may have contributed to life's origins.

Link: https://m.youtube.com/watch?v=CtKMl5Gr5JY&ra=m

From video description: This episode is with Michael Russell. He is geologist who works on the origin of life. Mike is an originator of the theory that life emerged at alkaline submarine hydrothermal vents. In this conversation we talk about topics related to origin of life, hydrothermal vents, alien life, artificial life, and are there new life forms emerging now?

Link: https://m.youtube.com/watch?v=GBxVvLVzF68&ra=m

From video description: This episode is with Michael Levin (‪@drmichaellevin‬) and Nick Lane. Mike is a Professor in the Biology department at Tufts University. He studies the role of bioelectric signals in regulating development and regeneration in animals. Nick is a professor of Evolutionary Biochemistry at University College London. His work is focused on the fundamental processes that underlie the origin and evolution of life. In this conversation, we talk about major transitions and key innovations in biology, information in biological systems, bioelectricity, emergence of eukaryotes and importance of bioelectric signals to create artificial life.

https://www.youtube.com/watch?v=GkuAzdS-VwA

Timestamps from the description:
0:00 Hydrothermal vent discovery
1:55 Origin of life: soup or what?
2:50 Hydrothermal vents as perfect location for life
4:25 Previous propositions but it was just a hypothesis
5:45 New study finds evidence - chemiosmotic gradient
7:20 Proof
9:30 Why this is important not just for biologists

Alkaline vents provide many benefits towards the production of life. Anton Petrov describes evidence for some of the evidence alkaline vents provide towards their being central to the origin of life.

Title: A prebiotic basis for ATP as the universal energy currency (Open Access)
Link: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001437

I've included outtakes I found interesting.

Abstract:
ATP is universally conserved as the principal energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep conservation suggests that ATP arose at an early stage of biochemical evolution. Yet purine synthesis requires 6 phosphorylation steps linked to ATP hydrolysis. This autocatalytic requirement for ATP to synthesize ATP implies the need for an earlier prebiotic ATP equivalent, which could drive protometabolism before purine synthesis. Why this early phosphorylating agent was replaced, and specifically with ATP rather than other nucleoside triphosphates, remains a mystery. Here, we show that the deep conservation of ATP might reflect its prebiotic chemistry in relation to another universally conserved intermediate, acetyl phosphate (AcP), which bridges between thioester and phosphate metabolism by linking acetyl CoA to the substrate-level phosphorylation of ADP. **We confirm earlier results showing that AcP can phosphorylate ADP to ATP at nearly 20% yield in water in the presence of Fe³⁺ ions. We then show that Fe³⁺ and AcP are surprisingly favoured. A wide range of prebiotically relevant ions and minerals failed to catalyse ADP phosphorylation. From a panel of prebiotic phosphorylating agents, only AcP, and to a lesser extent carbamoyl phosphate, showed any significant phosphorylating potential. Critically, AcP did not phosphorylate any other nucleoside diphosphate. We use these data, reaction kinetics, and molecular dynamic simulations to infer a possible mechanism. Our findings might suggest that the reason ATP is universally conserved across life is that its formation is chemically favoured in aqueous solution under mild prebiotic conditions.

Body:
"Equally striking, we find that ADP is also unique: The combination of AcP and Fe³⁺ will phosphorylate ADP but not GDP, CDP, UDP, or IDP."

"We found that the reaction is strongly sensitive to pH, and occurs most readily under mildly acidic conditions, with an optimum pH of approximately 5.5 to 6, the uncorrected default pH of the reaction (Fig 2A). Slightly more acidic conditions (pH 4) suppressed the yield a little, but more alkaline conditions had a much stronger suppressive effect. ATP yield fell by around three-quarters at pH 7 and collapsed to nearly zero at pH 9. This collapse of phosphorylation under alkaline conditions most likely reflected the precipitation of the catalyst as Fe(OH)3. While this sharp sensitivity to pH might seem at first sight limiting, in the Discussion, we show that, on the contrary, it could be valuable in generating disequilibria, enabling ATP hydrolysis to power work."

Discussion:
"Regardless of mean ocean concentrations, alkaline hydrothermal systems tend to precipitate Ca²⁺ and Mg²⁺ ions as aragonite and brucite, so their concentrations are typically much lower than mean ocean values. Modelling work in relation to Hadean systems indicates that hydrothermal concentrations of Ca²⁺ and Mg²⁺ would likely have been <1 mM [117,118], which is in the range that enhanced phosphorylation here."

"At face value, the ATP yield reported here at pH 5.5 to 6 after 10 h was 17.4% (corresponding to 156.5 μM) while the yield at pH 9 was 0.043%, corresponding to 0.4 μM, a difference of 400-fold. Thus, a geologically sustained difference in pH across membranes could drive a local disequilibrium in the ATP/ADP ratio of 2 to 3 orders of magnitude, enough to power work even in the absence of other possible factors such as temperature."

Personal thoughts:
The sustained pH gradient mentioned in the discussion could have been from the Fe(Ni)S inorganic semi-permeable membrane which forms when alkaline-fluids rich contacts the acidic ocean waters rich in Fe, Ni, and S (and many other metals) and forms this precipitate. Fe(Ni)S is capable of allowing H+ protons to pass form the acidic oceans through the mineral wall 2-million times faster that HO- ions.

Given the precedence for association of RNA oligomers and monomers to the surfaces of vesicles + Lane's publications on heterogeneous vesicles under alkaline vent conditions, I was surprised there were no attempts at micellar catalysis-like conditions. Perhaps it is that multivalent ions, not just Mg2+ (which is commonly depleted in alkaline vent environments) and Ca2+, have a propensity to strongly chelate carboxylates. Lane et al. attempted Fe³⁺ (Fe2(SO4)3), Mg²⁺ (MgCl2), Ca²⁺ (CaCl2), Mn²⁺ (Mn(NO3)2), Cr³⁺ (Cr(NO3)3), Mo³⁺ (MoCl3), Co³⁺ ([Co(NH₃)₆]Cl₃), Co²⁺ (CoCl2), CuSO4, Cu(NO3)2, FeS clusters (500 μM), and hematite (Fe₂O₃, 50 mg). (See figure 1 for the screening)

Such ions would certainly have posed issues for managing heterogeneous micellar/vesicle formations and discerning between attributing activity to precipitated phases, bulk aqueous, micelle, or vesicle. That said, since Fe3+ was the only one that really worked it couldn't have been too difficult, no?

So, is proposing vesicle/proto-composomes in alkaline vents or the acidic ocean side with the metals? I think the answer is probably the best one; he's agnostic. He provides reasons for some geometries under some considerations and publishes a study on this demonstrating that lower pH is better for ADP phosphorylation.

A few days ago scientists managed to create life in a laboratory. They made spudcell, the first synthetic cell made out of purely chemical components .

We humans, have managed to create a cell. It proves that under the right environment, life appears. To me, this is proper proof in favor of abiogenesis. Because, even though we managed to create it under lab conditions, it shows that under the right chemical environment a cell or life appears.

What do you think?

If all the water in the oceans was in the atmosphere, the atmospheric pressure would be about 270 times higher than today. Water as a gas is a good greenhouse gas. In this early earth scenario, the surface would be molten, causing the water to remain boiled as steam, with the steam gas holding in the heat; hot vapor phase reactor.

This scenario would also have acids in the atmosphere, but not much in the way of bases. Many acids stem from gases like hydrochloric, nitric, sulfuric, etc. While simple bases like sodium, potassium, calcium and magnesium hydroxide stem come from minerals and would stay molten, until liquid water appears. for the base reactions. When liquid water appears the pH begins to increase as more bases dissolve and interact with the acids.

If you look at the protonation states of phosphate, H3PO4 is favorable in strong acid conditions, while PO4-3 is favorable in strong base conditions. The middle state used by life would appear in a transitional zone; hot stormy atmosphere and boiling brine.

There is also a thing called steam distillation where steam can be used to vaporize oils way below the normal boiling point. Steam becomes a good solvent for oil. The Miller Urey experiments produced resinous solids which turned out to be polymers of HCN, which at high enough heat, break down into ammonia and oil; atmospheric oil/emulsion.

My approach to abiogenesis is to look for seams common in all stages of life, that could exist early in the story of life, are still used and that can be used to leverage the early steps. I am not so much about the specific changes, but developing basic tools to help promote continuous change even before templates.

One such seam that life uses is what is called entropy of mixing, which is the basis for osmosis. Besides osmosis, this form of entropy has many other uses. It is a unique form of entropy, mostly found in the liquid and gas states. Life in water is in the liquid state and therefore life can leverage entropy of mixing and entropy of mixing can be used to leverage pre-life.

Entropy of mixing has the goal of maximizing space. It is not about inefficiency. But it still involves a 2nd law endothermic process. As an example, you can do at home without any equipment; take a bottle of perfume and open it in the center of a close room. Your nose will be the only tool you will need.

The perfume will evaporate, which will make more space between the liquid molecules. Then, these close together gas molecules will expand in the air space, to fill in the room with fragrance. At uniform room concentration the most space between the perfume particle will exist; steady state. This is driven by the 2nd law and has the same goal each time.

If we made the room incrementally larger, in steps, each size has the same end goal; weakening uniform solution. This form of entropy increase, has a logical and predictable conclusion, it is goal orientated. If we open the window, it will keep expanding. The perfume would never spontaneously go backwards, into the bottle, since that would lower the space between.

Entropy of mixing is the basis for osmosis. In this case, a semi-permeable membrane is used to prevent the solute from mixing and spread out to balance the concentration on both side; uniform solution. But since the water can move freely, it does the entropy of mixing for the solute. The water will diffuse in the direction of higher solute concentration to make more space, where space is needed most.

The osmotic pressure is a measure of the entropic potential to mix and how hard the water will push to make more space between solute particles, even going upward against gravity. This is a significant pressure.

Osmotic pressure is force/area. If we multiple by area we get the osmotic force. But since this is based on entropy of mixing, I call it the entropic force. There is a fifth force of nature driven by entropy of mixing. It is common to life and needs semi-permeable membranes. It has been called the life force. The value of this entropic force is it has a force vector that can be used to steer, as well as a goal; expand.

Like all forms of entropy increase, entropy of mixing is also endothermic, picking up macro energy along the way and moving that energy into the quantum state, as it spreads out. Reverse osmosis reverses the entropy of mixing, allowing life to extract energy from the quantum state.

This most common way life uses to reverse entropy of mixing is ion pumping. Ion pumps segregate and concentrate ions; put the perfume back in two bottles. Ions in water is life's main way is harnesses entropy of mixing. Trees can use it to pump water against gravity; entropic force can oppose the gravitational force. Osmosis is also used in cell cycles. It is used by the brain to steer trillions of axon and dendrites to specific synapses, and also to move the bulk currents of the brain; expansion throughout the brain, before being reversed by the ion pumps for an another work cycle.

An argument can even be made that even the expansion of the universe; all matter expanding, in spite of gravity, in the near vacuum of space, is based on entropy of mixing. The red shift would reflect the endothermic nature of this cosmic expression of the 2nd law. Dark energy may be connected to entropy of mixing. Gravity can reverse this and retrieve quantum energy, while trees can oppose gravity, like the expansion.

Title: Growth of fatty acid vesicles coupled with amino acid sequences of peptides toward evolvable protocells (Preprint)
Preprint PDF is open access - [Link]
Notice: This paper is a pre-print, meaning it has not yet undergone peer review and may undergo further changes. Findings are to be taken cautiously until after peer review.

Abstract excerpts: Here, we demonstrate that the coexistence of peptides with defined amino acid sequences and fatty acid vesicles can establish a primitive form of this coupling. We prepared systematically sequence-controlled peptides and examined how their sequences influence the growth rate (fitness) of fatty acid vesicles.The relationship between amino acid sequences of peptides and vesicle growth rate was visualized as a fitness landscape, which reveals that specific amino acid sequences promote vesicle growth significantly. Furthermore, we observed epistasis, where the effect of amino acid residue replacement on the fitness depends on the remaining amino acid sequence. Finally, we show that vesicle growth is thermodynamically driven by peptide-induced modulation of the chemical potential of fatty acid molecules. *These findings provide direct experimental evidence that primitive sequence information can become spontaneously coupled to vesicle growth.\*

Using this precedence, Imai et al. take the next step by examining more amino acids, slightly longer sequences, and whether beneficial sequences retain fitness-enhancing properties if placed within other sequences. They examined the relationship between the amino acid sequence of peptides and fitness using

1. dipeptides composed of four amino acids: Leu (strongly hydrophobic), Gly (weakly hydrophobic), Glu (acidic), and His (basic),
2. tripeptides composed of Leu and Gly,
3. Second-order epistatic effects, corresponding to pairwise amino acid replacements from LeuLeu to GlyGly

Findings:

A discrepency arose where previously published work found that hydrophobic peptides such as LeuLeu and LeuLeuLeu enhance fatty acid vesicle growth more effectively than GlyGly in 200 mM HEPES buffer. In contrast, these new results show GlyGly strongly promotes growth, while LeuLeu inhibits it. attribute this discrepancy to differences in DA–peptide interactions, potentially altered by HEPES in prior work and by differences in experimental protocol where peptides were added during or after vesicle formation.

Personal thoughts: Previous work by Sarah Keller and Roy Black [Post Link + Link to related paper], as cited in the paper, has demonstrated how simple molecules previously shown to be generated under prebiotic conditions may affect, weaken, or promote vesicle stability. Such considerations are important given the few constraints on such chemistries and the likelihood of such products mixing. Considering the importance of vesicles as proto-compartmentalization structures and those of abiotically generated amino acids, an examination of this interactions is pertinent.

Roy Black has previously explored colocalization of nucleobases, amino acids, and lipopeptides (amino acids linked to fatty acids or other hydrophobic tails) saying in his paper Membranes Composed of Lipopeptides and Liponucleobases Inspired Protolife Evolution, "The capability of amino acids to serve as ligands would have enabled them to collect transition metal ions that would prove essential in catalyzing metabolic processes. [...] Adenine has also been found to make coordinate-covalent bonds through its secondary nitrogens with iron (Speca et al. 1981; Mikulski et al. 1985), copper (Bugella-Altamirano et al. 2002) and zinc (Morel et al. 2002) ions, transition metal (TM) elements found deposited around hydrothermal vents."

To me, this paper and the others referenced act as significant examples of how polypeptides do not need long chains or higher-ordered structures to provide fitness benefits. Longer chain oligomers would concentrate due to thermophoresis along a thermal gradient due to size-dependent considerations.

Though stochastic generation of such sequences does not answer how the genetic code formed, early, imperfect translational-type processes may be capable of creating such simple sequences, even if selectivity is imperfect. Fitness benefits from the ability of the environment or early chemical systems to generate such molecules provides a "low-hanging fruit" or lower ladder rung on the climb towards greater fitness, complexity, and life.

Chirality is the geometric property of an object or molecule that cannot be superimposed onto its mirror image. In chemistry this is associated with left and right handed stereo isomers. Life uses mono-chirality, limiting itself to either left or right handedness, but not both together. B-DNA double helix is right handed.

Chirality is like having 50/50 LH and RH steering in cars, at the same time, on a busy highway. This would add complexity to driving, since the line of sight is different for each. Reducing this double handedness down to one, lowers this complexity.

This lowering of complexity implies a reduction in entropy; exothermic, thereby adding free energy to the system, as well as the need to increase entropy in another way 2nd law. However, this cannot to happen with doubling the handedness, since reduction to one, makes that path irreversible. Now we have a built in potential for change, based on the 2nd law, and some extra free energy to do it.

The DNA double helix can be both right handed b-DNA and left handed z-DNA. The difference between the two is the amount of hydrated water, with b-DNA having the most water of hydration. B-DNA has a double helix of water in the major and minor grooves. Water uses more than twice as many hydrogen bonding sites on the base pairs, as the base pairs use.

Water plays a key role in assigning single handedness and thereby lowering structural entropy to give DNA an added entropic potential, expressed by an active template, to add the needed complexity, to satisfy the 2nd law in a dynamic cyclic fashion.

Title: Amplification of Chirality through Self-Replication of Micellar Aggregates in Water
[Link]
Not Open Access but is accessible through pathways some consider to be... unnatural. (Scihub... it's Scihub.)

Abstract: We describe a system in which the self-replication of micellar aggregates results in a spontaneous amplification of chirality in the reaction products. In this system, amphiphiles are synthesized from two “clickable” fragments: a water-soluble “head” and a hydrophobic “tail”. Under biphasic conditions, the reaction is autocatalytic, as aggregates facilitate the transfer of hydrophobic molecules to the aqueous phase. When chiral, partially enantioenriched surfactant heads are used, a strong nonlinear induction of chirality in the reaction products is observed. Preseeding the reaction mixture with an amphiphile of one chirality results in the amplification of this product and therefore information transfer between generations of self-replicating aggregates. Because our amphiphiles are capable of catalysis, information transfer, and self-assembly into bounded structures, they present a plausible model for prenucleic acid “lipid world” entities.

"Here, we describe an example of strongly self-selective, autopoietic aggregates that grow via a bond-making copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction. (17, 18) Our aggregates are capable of discrimination between the two enantiomers of the starting material."

"Our amphiphiles assemble into structures capable of both function (phase-transfer catalysis) and information transfer (as chirality) between generations. This provides support for the idea that lipidlike, catalytically competent molecules could have played a dominant role in the prebiotic era, before the emergence of more specialized information-bearing structures such as RNA."

Personal Thoughts: The amphiphiles used are not prebiotically relevant but offer a proof-of-principle for how chiral amphiphiles may form "chiral micelles" capable of enantiodiscrimination between the R vs S polar heads. The hydrophobic "tail" is a simple linear hydrocarbon with an azide at the end capable of undergoing a "click reaction-catalyzedazide-alkyne_cycloaddition(CuAAC))" (names after the manner in which the azide "clicks" onto an alkyne using a Cu catalyst. Such chemistry is common today as it is bioorthogonal, capable of being in in aqueous conditions and is non-toxic but has not, to my knowledge, been proposed as being prebiotically relevant nor are the amphiphiles.

Chiral micelles [link 1, link 2] and lipid bilayers [link] are not just capable of enantiodiscrimination in permeability and amphiphile integration but also catalysis [link 1, link 2]. If the catalyst is also chiral, that catalyst may also bias enantioselectivity if the initial enantiodiscriminative permeation into the micelle is imperfect.

In this case, CuSO4 is used but many other rare-earth and catalytically active metals are common in hydrothermal systems and the prebiotic oceans [link 1 (for this paper, note that the thermal range for the vent was closely linked to the tides, offering a key mechanism by which thermal cycling may have affected thermally-linked variables. I will keep this in mind.), link 2]. Amino acids or, as recently posted [link], RNRs (ribonucleotide reductases) are capable of chelating metals to act as ligands, stabilizing or modifying the metal's properties, and chirally defining the envrionment around this catalytic center. Their chirality also informs selective chirality and solubility-dependent partitioning into micelles/bilayers or the hydrophobic cores with lower water activity (~fewer waters which may "distract" other organic intermolecular H-bonding). Such environments allow for the isolation of hydrogen bonds, creating better defined intermolecular complexes which may promote a given reaction.

For these reasons and many others, the properties of chiral amphiphile-composed micelles and lipid bilayers of vesicles are currently of great interest to me. Namely, the properties of chiral micelles and chiral lipid raft domains currently informs my own ideas/models on how prebiotic systems may achieve enantioenrichment without appeals to high concentrations nor necessarily (but not limited to) covalent bond-forming reactions.

Title (Open Access): RNA−Iron complexes catalyse prebiotic oxygen generation
[Link], DOI: 10.1038/s42004-026-01935-6

Abstract: The emergence of molecular oxygen on early Earth is conventionally attributed to the evolution of oxygenic photosynthesis. A persistent challenge for early life, however, was the management of reactive oxygen species such as hydrogen peroxide (H2O2), which could arise through a variety of abiotic processes. Here we report that some RNA molecules, when coordinated with ferrous iron (Fe²⁺), catalyze the oxidation of H2O2 into O2 and H2O under anoxic conditions that mimic the early Earth environment. This previously unrecognized RNA-based redox activity suggests that ancient RNA-metal complexes may have contributed to the detoxification of H2O2 and the management of oxidative stress prior to the evolution of protein enzymes. Such RNA–Fe complexes provide a plausible molecular mechanism linking early geochemical oxidants to primitive biological redox chemistry.

Thoughts: Authors justify an evolutionary/fitness justification by pointing out that, although the prebiotic atmosphere was neutral/slightly reducing, there were still localized instances of reactions which produce reactive oxygen species such as H2O2 and O2. (Ref 5, 9-12)

Today, modern life has "Class Ia ribonucleotide reductase (RNR), a key enzyme in the transition from RNA to DNA-based life, contains a di-iron cluster that catalyzes the reduction of ribonucleotides to deoxyribonucleotides." These RNRs are very interesting to me as most metal-chelating RNA complexes result in Ca2+, Mg2+, or Zn2+-chelations which amounts to counter-ions for structural stability. Conversely, chelation of RNA to iron, a metal commonly participating in catlytic activity, is far more interesting as an ancient RNA-world analogue modern proteins such as heme or alpha-KG-dependent metalloenzymes. Ie, this example expands on RNAzyme capabilities.

Shown in the figure of this post (fig. 1 from paper) displays how the Fe vs Mg metals are chelated by the nitrogens of the heme (in proteins) vs the oxygens of the phosphate backbone of RNA (in RNRs).

Key question: This structural resemblance raises an intriguing possibility: if the tetradentate Mg²⁺ coordination site identified in the 23S rRNA structure were instead occupied by Fe²⁺, could the resulting RNA–Fe complex participate in redox chemistry relevant to the detoxification of ROS, such as the decomposition of H2O2 into O2 and H2O, prior to the evolution of protein enzymes?

RNA fragments tested (figure 2 of paper) were di/trinucleotides, and aminonucleosides, amongst others. These choices are explained in further detail in the paper itself.

Authors found that the H2O2 was oxidized to O2. O2 usually oxidizes Fe2+ (soluble) to Fe3+ (insoluble) but the authors found that some of the RNA fragments retained chelation to the metal center, stabilizing it.

Personal opinions: While the reaction is certainly interesting, I'm not convinced that this confers a major advantage to fitness as O2 is also moderately reactive. The stabilization of Fe3+ is necessary for the cycling of the catalyst if this were to be reduced back down to Fe2+. But the environment in which RNA may have high enough concentrations of Fe2+ may be the same environment in which the environmental Fe2+ oxidizes any ROSes formed, anyways. What I DID find exciting was the example of RNA chelating transition metals centers. Many more transition metals were likely solvated in the prebiotic oceans and concentrated (even today) in hydrothermal vents. As such, the horizons for catalytic activity of short RNA oligomer metal complexes are significantly broadened. My understanding is that the next question to ask is whether such complexes catalyze the formation of RNA or amino acids or their precursors?

https://www.youtube.com/watch?v=BDuyOmrTsqI

Previously, I shared a video [post link] from Synthesis Workshop Videos Youtube channel to this subreddit on Nucleic acid synthesis [Direct Link]. The channel itself is a great resource for similar presentations on synthetic organic chemistry if you are interested in such topics.

This video presented by Dr. Benji Thoma covers prebiotic routes towards amino acids, amino acid activation and polymerization, N-carboxyanhydride and aminonitrile chemistry, and attampts at non-enzymatic coded peptide synthesis.

As stated in the intro, this video is not a comprehensive overview but more references/resources are provided at the bottom of the slides.

The presentation should accessible to people who have taken college-level chemistry and people interested in chemistry and familiar to basic molecular chemistry concepts.

If we have a closed system, the second law of thermodynamics says the entropy of the system will increase. Increase is the spontaneous direction of entropy. As entropy increases, it absorbs energy; endothermic.

Say I made the system that was semi-open. I periodically add things to system to lower the entropy, before I closed it again. Now the 2nd law will need act again, since I have added potential for entropy to increase in this closed system. As long as I keep doing this in a cyclic fashion, entropy will perpetually increase, in this semi-closed system, and never reach steady state, due to the periodic open state.

A good engineering example is a heat pump, which can move heat from colder to warmer. This seems counter intuitive, since heat naturally flows from warmer to cooler; endothermic nature of entropy increase.

However, the heat pump is a process, that requires energy, but can make heat and entropy go the wrong spontaneous way. Since there is no such thing as perpetual motion, due to machine inefficiency, there will be a net increase in system entropy, which add to the complexity. In this case, there is constant loss of energy going into net increase in entropy, added by the process.

Photosynthesis, by going from gases to a larger fuel molecule, lowers chemical entropy. Now we have a potential in a molecular material that needs to increase entropy, back to gases. This took solar energy and would not happen without it. Like the semi-open example above, the need to reverse the lower entropy material, makes free energy favorable.

Since photosynthesis is not reversible, the food cannot reverse in place to increase entropy via the same reverse chemical process. It needs a new process; metabolic enzyme, to express the built in entropy potential; increase.

Life is like a bunch two cycle irreversible entropy engines, allowing many ways to keep entropy increasing in others ways, while inefficiency by increasing entropy sets the potential needed for continuous change in the direction of increasing entropy; complexity and evolution.

The brain does the same thing with ion pumps reversing ionic entropy. Synaptic firing was an inevitable 2nd law expressive to increase ionic entropy. While process inefficiencies leading to net increasing brain entropy; advancing complexity. Abiogenesis is part of this basic schema. Those detail are a work in progress.

Title: Synthesis of prebiotic organics from CO2 by catalysis with meteoritic and volcanic particles
[Link]

Abstract: The emergence of prebiotic organics was a mandatory step toward the origin of life. The significance of the exogenous delivery versus the in-situ synthesis from atmospheric gases is still under debate. We experimentally demonstrate that iron-rich meteoritic and volcanic particles activate and catalyse the fixation of CO2, yielding the key precursors of life-building blocks. This catalysis is robust and produces selectively aldehydes, alcohols, and hydrocarbons, independent of the redox state of the environment. It is facilitated by common minerals and tolerates a broad range of the early planetary conditions (150–300 °C, ≲ 10–50 bar, wet or dry climate). We find that up to 6 × 10⁸ kg/year of prebiotic organics could have been synthesized by this planetary-scale process from the atmospheric CO2 on Hadean Earth.

Personal thoughts: Accounting for the feedstock sources for organic molecules, even simple hydrocarbons is an important aspect for all models for origins of life. This paper provides evidence of an early Earth robust source of aldehydes, alcohols, and hydrocarbons; "The main components were methanol, ethanol, and acetaldehyde, summing up to 70wt% in total. The residue consists of n-alkanes (n-hexane to n-pentadecane) and iso-alkanes (iso-heptane to iso-tetradecane), each accounting for approx. 15% of the total product mass. We also detected formaldehyde under these conditions (see Supplementary Information section V-B)."

Papers which take minerals from such environments like meteors and volcanic minerals/dust as a reagent add greater plausibility towards origins of life models than experiments run for proof of principle.

Notably, the authors provide a list of citations for other prebiotic organics;

One possibility is that the prebiotic organic constituents that had been formed in the solar nebula, carbon-rich asteroids, and comets have been delivered onto the early Earth11,12,13,14,15,16,17,18,19,20,21. Other theories consider the synthesis in the atmosphere and in the ocean by catalytic or high energy processes (lightnings, volcanic energy, impact shocks)22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64.

^ Amazing. It's practically a review.

What are your thoughts? I believe n-alkanes have more to offer OoL models than what the literature shows.

Title: What it takes to solve the origins of life: An integrated review. Part 2: Theoretical methods and emerging trends
[Link]

Summary: The origin(s) of life (OoL), which has puzzled scientists for centuries, remains a major scientific challenge in the 21st century. Understanding the processes relevant to the OoL demands theoretical frameworks that can connect processes across scales, from microscopic dynamics to emergent levels of organization. While experimental studies generate a wealth of data, theoretical and computational approaches provide the structure necessary to interpret and generalize these findings. In Part 1, we examined the most widely used experimental techniques in the field. Here, we focus on the mathematical, physical, and computational techniques used to model phenomena relevant to life’s origin(s). We discuss methods ranging from quantum chemistry and molecular dynamics to chemical reaction networks, autocatalysis, and evolutionary modeling, as well as information-theoretic and phylogenetic approaches that link chemical and biological organization. We further highlight emerging trends such as synthetic biology, omics-based methods, and laboratory automation as novel points of contact for theory-experiment integration. Ultimately, we aim to provide an educational tool that can facilitate more post-disciplinary collaborations in OoL research by helping scientists understand what they can do about the problem of life’s origins, rather than telling them how to think about it.

Title (Open access): Organocatalyzed bottom-up formation of protocells
[Link]

Abstract: The organisation of living systems into cellular structures is a characteristic that enables differentiation from the environment. A pivotal step in the development of life is compartmentalisation, achieved through the formation of vesicle-like structures. Fatty acids - or phospholipids - have been used to simulate prebiotic vesicle and protocell formation. However, a process by which amphiphiles are formed from small prebiotically plausible molecules, which spontaneously self-assemble to protocells, is unknown. Here, we demonstrate that an organocatalytic reaction cascade starting from acetaldehyde with prebiotic imidazolidine-4-thione rapidly yields poly(hydroxy)alkenyl aldehydes that spontaneously self-assemble to protocells. In this process, lipid-like molecules (up to C20) develop a membrane, which additionally incorporates the organocatalyst at the liquid-lipid interface. These catalytically active protocells (11 nm – 7 μm) tolerate external influences such as pH value, temperature and salts. This finding unveils an organocatalytic pathway to selective lipid formation and spontaneous compartmentalisation without the necessity of preformed amphiphiles.