https://reasonandscience.catsboard.com/t2865-rna-dna-it-s-prebiotic-synthesis-impossible
RNA & DNA: It's prebiotic synthesis: Impossible !! Part 1
https://www.youtube.com/watch?v=-ZFlmL_BsXE
RNA & DNA: It's prebiotic synthesis: Impossible !! Part 2
https://www.youtube.com/watch?v=dv4mUjmuRRU
Main points addressed in the video
Synthesis of nitrogenous bases in prebiotic environments
- High-energy precursors to produce purines and pyrimidines would have had to be produced in a sufficiently concentrated form. There is no known prebiotic route to this.
- Scientists have failed to produce cytosine in spark-discharge experiments, nor has cytosine been recovered from meteorites or extraterrestrial sources. The deamination of cytosine and its destruction by other processes such as photochemical reactions place severe constraints on prebiotic cytosine syntheses.
- The origin of guanine bases has proven to be a particular challenge. While the other three bases of RNA could be created by heating a simple precursor compound in the presence of certain naturally occurring catalysts, guanine had not been observed as a product of the same reactions.
- Adenine synthesis requires unreasonable Hydrogen cyanide concentrations. Adenine deaminates 37°C with a half-life of 80 years. Therefore, adenine would never accumulate in any kind of "prebiotic soup." The adenine-uracil interaction is weak and nonspecific, and, therefore, would never be expected to function in any specific recognition scheme under the chaotic conditions of a "prebiotic soup."
- Uracil has also a half-life of only 12 years at 100◦C. For nucleobases to accumulate in prebiotic environments, they must be synthesized at rates that exceed their decomposition.
Ribose: Synthesis problems of the Pentose 5 carbon sugar ring
The best-studied mechanism relevant to the prebiotic synthesis of ribose is the formose reaction. Several problems have been recognized for the ribose synthesis via the formose reaction. The formose reaction is very complex. It depends on the presence of a suitable inorganic catalyst. Ribose is merely an intermediate product among a broad suite of compounds including sugars with more or fewer carbons.
The phosphate group
On prebiotic earth, however, there would have been no way to activate phosphate somehow, in order to promote the energy dispendious reaction.
Prebiotic RNA and DNA synthesis
1. No prebiotic mechanism is known to select:
- Right-handed configurations of RNA and DNA
- The right backbone sugar
- How to get size complementarity of the nucleotide bases to form a DNA strand and strands of the DNA molecule running in the opposite directions
2. Bringing all the parts together and joining them in the right position
- Attach the nucleic bases to the ribose and in a repetitive manner at the same, correct place, and the backbone being a repetitive homopolymer
- Prebiotic glycosidic bond formation between nucleosides and the base
- Prebiotic phosphodiester bond formation
- Fine-tuning of the strength of the hydrogen base pairing forces
3. The instability, degradation, and asphalt problem
- Bonds that are thermodynamically unstable in water, and overall intrinsic instability. RNA’s nucleotide building blocks degrade at warm temperatures in time periods ranging from nineteen days to twelve years. These extremely short survival rates for the four RNA nucleotide building blocks suggest why life’s origin would have to be virtually instantaneous—all the necessary RNA molecules would have to be assembled before any of the nucleotide building blocks decayed.
4. The energy problem
- Doing things costs energy. There has to be a ready source of energy to produce RNA. In modern cells, energy is consumed to make RNA.
5. The minimal nucleotide quantity problem.
- The prebiotic conditions would have had to be right for reactions to give perceptible yields of bases that could pair with each other.
6. The Water Paradox
- The hydrolytic deamination of DNA and RNA nucleobases is rapid and irreversible, as is the base-catalyzed cleavage of RNA in water. This leads to a paradox: RNA requires water to do its job, but RNA cannot emerge in water and cannot replicate with sufficient fidelity in water without sophisticated repair mechanisms in place.
7.The transition problem from prebiotic to biochemical synthesis
- Even if all this in a freaky accident occurred by random events, that still says nothing about the huge gap and enormous transition that would be still ahead to arrive at a fully functional interlocked and interdependent metabolic network, where complex biosynthesis pathways produce nucleotides in modern cells.
Unguided prebiotic synthesis of RNA and DNA: an unsolved riddle!
I think, to say that on average the 14 hurdles that it would take to make primed nucleotides would each take 10 unit operations - that at least 140 little events would have to be appropriately sequenced. Unguided, the appropriate thing happened at each point on one occasion in six.The odds against a successful unguided synthesis of a batch of primed nucleotide on the primitive Earth would be a huge number, represented approximately by a 1 followed by 109 zeros ( 10^109). 'The odds are enormous against its being coincidence. No figures could express them.'
Synthesis of nitrogenous bases in prebiotic environments
- High-energy precursors to produce purines and pyrimidines would have had to be produced in a sufficiently concentrated form. There is no known prebiotic route to this.
- Scientists have failed to produce cytosine in spark-discharge experiments, nor has cytosine been recovered from meteorites or extraterrestrial sources. The deamination of cytosine and its destruction by other processes such as photochemical reactions place severe constraints on prebiotic cytosine syntheses.
- The origin of guanine bases has proven to be a particular challenge. While the other three bases of RNA could be created by heating a simple precursor compound in the presence of certain naturally occurring catalysts, guanine had not been observed as a product of the same reactions.
- Adenine synthesis requires unreasonable Hydrogen cyanide concentrations. Adenine deaminates 37°C with a half-life of 80 years. Therefore, adenine would never accumulate in any kind of "prebiotic soup." The adenine-uracil interaction is weak and nonspecific, and, therefore, would never be expected to function in any specific recognition scheme under the chaotic conditions of a "prebiotic soup."
- Uracil has also a half-life of only 12 years at 100◦C. For nucleobases to accumulate in prebiotic environments, they must be synthesized at rates that exceed their decomposition.
Ribose: Synthesis problems of the Pentose 5 carbon sugar ring
The best-studied mechanism relevant to the prebiotic synthesis of ribose is the formose reaction. Several problems have been recognized for the ribose synthesis via the formose reaction. The formose reaction is very complex. It depends on the presence of a suitable inorganic catalyst. Ribose is merely an intermediate product among a broad suite of compounds including sugars with more or fewer carbons.
The phosphate group
On prebiotic earth, however, there would have been no way to activate phosphate somehow, in order to promote the energy dispendious reaction.
1. No prebiotic mechanism is known to select:
- Right-handed configurations of RNA and DNA
- The right backbone sugar
- How to get size complementarity of the nucleotide bases to form a DNA strand and strands of the DNA molecule running in the opposite directions
2. Bringing all the parts together and joining them in the right position
- Attach the nucleic bases to the ribose and in a repetitive manner at the same, correct place, and the backbone being a repetitive homopolymer
- Prebiotic glycosidic bond formation between nucleosides and the base
- Prebiotic phosphodiester bond formation
- Fine-tuning of the strength of the hydrogen base pairing forces
3. The instability, degradation, and asphalt problem
- Bonds that are thermodynamically unstable in water, and overall intrinsic instability. RNA’s nucleotide building blocks degrade at warm temperatures in time periods ranging from nineteen days to twelve years. These extremely short survival rates for the four RNA nucleotide building blocks suggest why life’s origin would have to be virtually instantaneous—all the necessary RNA molecules would have to be assembled before any of the nucleotide building blocks decayed.
4. The energy problem
- Doing things costs energy. There has to be a ready source of energy to produce RNA. In modern cells, energy is consumed to make RNA.
5. The minimal nucleotide quantity problem.
- The prebiotic conditions would have had to be right for reactions to give perceptible yields of bases that could pair with each other.
6. The Water Paradox
- The hydrolytic deamination of DNA and RNA nucleobases is rapid and irreversible, as is the base-catalyzed cleavage of RNA in water. This leads to a paradox: RNA requires water to do its job, but RNA cannot emerge in water and cannot replicate with sufficient fidelity in water without sophisticated repair mechanisms in place.
7.The transition problem from prebiotic to biochemical synthesis
- Even if all this in a freaky accident occurred by random events, that still says nothing about the huge gap and enormous transition that would be still ahead to arrive at a fully functional interlocked and interdependent metabolic network, where complex biosynthesis pathways produce nucleotides in modern cells.
Synthesis of nitrogenous bases in prebiotic environments
- High-energy precursors to produce purines and pyrimidines would have had to be produced in a sufficiently concentrated form. There is no known prebiotic route to this.
- Scientists have failed to produce cytosine in spark-discharge experiments, nor has cytosine been recovered from meteorites or extraterrestrial sources. The deamination of cytosine and its destruction by other processes such as photochemical reactions place severe constraints on prebiotic cytosine syntheses.
- The origin of guanine bases has proven to be a particular challenge. While the other three bases of RNA could be created by heating a simple precursor compound in the presence of certain naturally occurring catalysts, guanine had not been observed as a product of the same reactions.
- Adenine synthesis requires unreasonable Hydrogen cyanide concentrations. Adenine deaminates 37°C with a half-life of 80 years. Therefore, adenine would never accumulate in any kind of "prebiotic soup." The adenine-uracil interaction is weak and nonspecific, and, therefore, would never be expected to function in any specific recognition scheme under the chaotic conditions of a "prebiotic soup."
- Uracil has also a half-life of only 12 years at 100◦C. For nucleobases to accumulate in prebiotic environments, they must be synthesized at rates that exceed their decomposition.
Ribose: Synthesis problems of the Pentose 5 carbon sugar ring
The best-studied mechanism relevant to the prebiotic synthesis of ribose is the formose reaction. Several problems have been recognized for the ribose synthesis via the formose reaction. The formose reaction is very complex. It depends on the presence of a suitable inorganic catalyst. Ribose is merely an intermediate product among a broad suite of compounds including sugars with more or fewer carbons.
The phosphate group
On prebiotic earth, however, there would have been no way to activate phosphate somehow, in order to promote the energy dispendious reaction.
Unguided prebiotic synthesis of RNA and DNA: an unsolved riddle!
The origin of the RNA and DNA molecule is an origin of life problem, not evolution.
Steve Benner, one of the world’s leading authorities on abiogenesis: The “origins problem” CANNOT be solved.
Graham Cairns-Smith: The odds against a successful unguided synthesis of a batch of primed nucleotide on the primitive Earth would be a huge number, represented approximately by a 1 followed by 109 zeros ( 10^109). 'The odds are enormous against its being coincidence. No figures could express them.'
Tan, Change; Stadler, Rob. The Stairway To Life
The longest chains (up to fifty monomers) and the highest production of molecules with the correct bonds have been achieved in the presence of montmorillonite clay. With purine nucleotides (adenosine and guanine), the percentage of correct phosphodiester bonds actually exceeded that of the incorrect bonds. However, the addition of each monomer to the chain comes with a probability of incorrect bonding, and one incorrect bond irreversibly destroys the homolinkage of the growing polymer, just as a train with one derailed boxcar can destroy the entire train. Therefore, the synthetic yield of biopolymers with the desired homolinkage decreases exponentially as the length of the biopolymer increases—even when starting only with pure building blocks.
In the presence of montmorillonite, polymerization of purine nucleotides (i.e., adenine and guanine) is favored over pyrimidine nucleotides (i.e., cytosine, thymine, and uracil) . This would constrain the potential information-carrying capacity of the resulting polymers, somewhat like requiring an author to have the letters A through M appear in their writing twice as often as the letters N through Z.
Another issue with the montmorillonite-catalyzed reaction is that the most successful polymerization occurred with an inosine nitrogenous base, which is not used to synthesize natural DNA or RNA. Also, the resulting oligomers decompose in the presence of water and the clay accelerates this decomposition.
Production of DNA with perfect homolinkage throughout the length of a genome (for example, there are approximately 500,000 nucleotides in the simplest known free-living organism’s genome) is impossible without the molecular machinery that is available only in living organisms.
An E. coli cell is about two micrometers long (two millionths of a meter) and one micrometer in diameter, and it contains a circular DNA molecule with 4.6 million base pairs. If fully extended, the DNA molecule would measure about 1.4 millimeters, or about 700 times longer than the E. coli cell. Picture your car, representing an E. coli, containing a rope that represents the DNA. Scaling up the E. coli to become the size of your car (about five meters or sixteen feet in length), the DNA would correspondingly scale up to approximately 3.5 kilometers or 2.2 miles of rope with a diameter of six millimeters or ¼ inch, contained in your car. Indeed, all of that DNA has to be compressed to fit within each bacterial cell. Now, imagine the E. coli cell duplicating this DNA before replication and needing to separate the two interlinked copies before cell division. Genomic DNAs are so long that they cannot fit into any cells without being highly compacted with the help of multiple proteins. Also, such a length of rope cannot be manipulated without kinking and supercoiling, especially when DNA is unwound for reproduction. Additional topoisomerase enzymes and structural maintenance of chromosome (SMC) proteins are essential for this purpose.
Prof. Steven A. Benner: When Did Life Likely Emerge on Earth in an RNA-First Process? 24 September 2019
All of these path‐hypotheses involve relatively reduced organic molecules that serve as the precursors of the four standard RNA nucleobases (guanine, adenine, cytosine, and uracil) or “grandfather′s axe” heterocycles (not shown). Thus, all assume the production of substantial amounts of reduced primary precursors, likely in the Hadean atmosphere (before 4 billion years ago). These primary precursors include hydrogen cyanide (HCN), cyanamide (H2NCN), cyanoacetylene (HCCCN), cyanogen (NCCN), ammonia (NH3), and cyanic acid (HCNO). Further, they all assume that these (or their downstream products) avoided dilution into a global ocean, perhaps by adsorbing on solids, or by delivery to sub‐aerial land with a constrained aquifer. Most chemical path‐hypotheses to create RNA prebiologically all but require an atmosphere that is more reducing than what planetary accretion models suggest was the norm above the Hadean Earth.
https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/syst.201900035
Prof. Steven A. Benner: Asphalt, Water, and the Prebiotic Synthesis of Ribose, Ribonucleosides, and RNA 2012
Some bonds in RNA appear to be “impossible” to form under any conditions considered plausible for early Earth
https://pubs.acs.org/doi/abs/10.1021/ar200332w
Henderson James Cleaves: One Among Millions: The Chemical Space of Nucleic Acid-Like Molecules September 9, 2019
Various types of nucleic acid-like molecules have been enumerated and synthesized, but this is the first systematic attempt to enumerate, quantify and describe this chemical space. This space is surprisingly large, though its size appears predictable by typical isomerism studies. It is remarkable, given the existence of this structure space, that biology found a solution to the need for information storage. Is the solution life found to genetic molecular information storage optimal? In one sense obviously yes: it works very well and has managed to robustly support biological evolution over 3.5-4 Ga of planetary change. In another sense, from the standpoint of xeno- and synthetic biology, could other, perhaps equally good, or even better genetic systems be devised? The answer to this question will require sophisticated and protracted chemical experimentation. Studies to date suggest that the answer could be no. Many nearly as good, some equally good, and a few stronger base-pairing analogue systems are known.
https://pubs.acs.org/doi/10.1021/acs.jcim.9b00632
Graham Cairns-Smith: Genetic takeover, page 66:
Now you may say that there are alternative ways of building up nucleotides, and perhaps there was some geochemical way on the early Earth. But what we know of the experimental difficulties in nucleotide synthesis speaks strongly against any such supposition. However it is to be put together, a nucleotide is too complex and metastable a molecule for there to be any reason to expect an easy synthesis. If you were to consider in more detail a process such as the purification of an intermediate ( to form amide bonds between amino acids and nucleotides ) you would find many subsidiary operations — washings, pH changes and so on. (Remember Merrifield’s machine: for one overall reaction, making one peptide bond, there were about 90 distinct operations required.)
https://3lib.net/book/2797668/0495a0
A. Graham Cairns-Smith: Chemistry and the Missing Era of Evolution
What is missing from this story of the evolution of life on earth is the original means of producing such sophisticated materials as RNA. The main problem is that the replication of RNA depends on a clean supply of rather complicated monomers—activated nucleotides. What was required to set the scene for an RNA world was a highly competent, long-term means of production of at least two nucleotides. In practice the discrimination required to make nucleotide parts cleanly, or to assemble them correctly, still seems insufficient.
https://sci-hub.ren/10.1002/chem.200701215
Let us consider some of the difficulties to make RNA & DNA
1. as we have seen, it is not even clear that the primitive Earth would have generated and maintained organic molecules. All that we can say is that there might have been prevital organic chemistry going on, at least in special locations.
2. highenergy precursors of purines and pyrimidines had to be produced in a sufficiently concentrated form (for example at least 0.01 M HCN).
3. the conditions must now have been right for reactions to give perceptible yields of at least two bases that could pair with each other.
4. these bases must then have been separated from the confusing jumble of similar molecules that would also have been made, and the solutions must have been sufficiently concentrated.
5. in some other location a formaldehyde concentration of above 0.01 M must have built up.
6. this accumulated formaldehyde had to oligomerise to sugars.
7. somehow the sugars must have been separated and resolved, so as to give a moderately good concentration of, for example, D-ribose.
8. bases and sugars must now have come together.
9. Ninth, they must have been induced to react to make nucleosides. (There are no known ways of bringing about this thermo dynamically uphill reaction in aqueous solution: purine nucleosides have been made by dry phase synthesis, but not even this method has been successful for condensing pyrimidine bases and ribose to give nucleosides
10. Whatever the mode of joining base and sugar it had to be between the correct nitrogen atom of the base and the correct carbon atom of the sugar. This junction will fix the pentose sugar as either the a- or fl-anomer of either the furanose or pyranose forms. For nucleic acids it has to be the fl-furanose. (In the dry-phase purine nucleoside syntheses referred to above, all four of these isomers were present with never more than 8 ‘Z, of the correct structure.)
11. phosphate must have been, or must now come to have been, present at reasonable concentrations. (The concentrations in the oceans would have been very low, so we must think about special situations—evaporating lagoons and such things
12. the phosphate must be activated in some way — for example as a linear or cyclic polyphosphate — so that (energetically uphill) phosphorylation of the nucleoside is possible.
13. to make standard nucleotides only the 5’- hydroxyl of the ribose should be phosphorylated. (In solid-state reactions with urea and inorganic phosphates as a phosphorylating agent, this was the dominant species to begin with. Longer heating gave the nucleoside cyclic 2’,3’-phosphate as the major product although various dinucleotide derivatives and nucleoside polyphosphates are also formed
14. if not already activated — for example as the cyclic 2’,3’-phosphate — the nucleotides must now be activated (for example with polyphosphate) and a reasonably pure solution of these species created of reasonable concentration. Alternatively, a suitable coupling agent must now have been fed into the system.
15. the activated nucleotides (or the nucleotides with coupling agent) must now have polymerised. Initially this must have happened without a pre-existing polynucleotide template (this has proved very difficult to simulate ; but more important, it must have come to take place on pre-existing polynucleotides if the key function of transmitting information to daughter molecules was to be achieved by abiotic means. This has proved difficult too. Orgel & Lohrmann give three main classes of problem.
(i) While it has been shown that adenosine derivatives form stable helical structures with poly(U) — they are in fact triple helixes — and while this enhances the condensation of adenylic acid with either adenosine or another adenylic acid — mainly to di(A) - stable helical structures were not formed when either poly(A) or poly(G) Were used as templates.
(ii) It was difficult to find a suitable means of making the internucleotide bonds. Specially designed water-soluble carbodiimides were used in the experiments described above, but the obvious pre-activated nucleotides — ATP or cyclic 2’,3’-phosphates — were unsatisfactory. Nucleoside 5'-phosphorimidazolides, for example: N/\ n K/N/P-r’o%OHN/\N were more successful, but these now involve further steps and a supply of imidazole, for their synthesis.
(iii) Internucleotide bonds formed on a template are usually a mixture of 2’—5’ and the normal 3’—5’ types. Often the 2’—5’ bonds predominate although it has been found that Zn“, as well as acting as an eflicient catalyst for the templatedirected oligomerisation of guanosine 5’-phosphorimidazolide also leads to a preference for the 3’—5’ bonds.
16. the physical and chemical environment must at all times have been suitable — for example the pH, the temperature, the M2+ concentrations.
17. all reactions must have taken place well out of the ultraviolet sunlight; that is, not only away from its direct, highly destructive effects on nucleic acid-like molecules, but away too from the radicals produced by the sunlight, and from the various longer lived reactive species produced by these radicals.
18. unlike polypeptides, where you can easily imagine functions for imprecisely made products (for capsules, ionexchange materials, etc), a genetic material must work rather well to be any use at all — otherwise it will quickly let slip any information that it has managed to accumulate.
19. what is required here is not some wild one-off freak of an event: it is not true to say ‘it only had to happen once’. A whole set-up had to be maintained for perhaps millions of years: a reliable means of production of activated nucleotides at the least.
As the difficulties accumulate the stakes get higher: success would be all the more resounding, but it becomes less likely. Sooner or later it becomes wiser to put your money elsewhere.

Richard Van Noorden: RNA world easier to make 13 May 2009
Although Sutherland has shown that it is possible to build one part of RNA from small molecules, objectors to the RNA-world theory say the RNA molecule as a whole is too complex to be created using early-Earth geochemistry. "The flaw with this kind of research is not in the chemistry. The flaw is in the logic — that this experimental control by researchers in a modern laboratory could have been available on the early Earth," says Robert Shapiro
Shapiro sides with supporters of another theory of life's origins – that because RNA is too complex to emerge from small molecules, simpler metabolic processes, which eventually catalysed the formation of RNA and DNA, were the first stirrings of life on Earth. Sutherland, though, hopes that ingenious organic chemistry might provide an RNA synthesis so convincing that it effectively serves as proof. "We might come up with something so coincidental that one would have to believe it," he says. "That is the goal of my career."
https://www.nature.com/articles/news.2009.471
Robert Shapiro: Life: What A Concept! 2008
SHAPIRO: Since then, so-called prebiotic chemistry, which is of course falsely named, because we have no reason to believe that what they're doing would ever lead to life — I just call it 'investigator influenced abiotic organic chemistry' — has fallen into the same trap. In the proceedings of the National Academy of Sciences about two months ago there was a paper — I think it was theoretical — they showed that in certain hydro-thermal events, convection forces and other attractive forces, about which I am unable to comment, would serve to concentrate organic molecules, so that organic molecules would get much more concentrated in the bottom of this than they would in the ordinary ocean. Very nice, perhaps it's a good place for the origin of life, and interesting finding, but then there was another commentary paper in the Proceedings by another invited commentator, who said, Great advance for RNA world because if you put nucleotides in, they'll be concentrated enough to form RNA; and if you put RNA in, the RNA will come together and form aggregates, giving you much more chance of forming a ribosome or whatever. I looked at the paper and thought, How did nucleotides come in? How did RNA come in? How did anything come in? The point is, you would take whatever mess prebiotic chemistry gives you and you would concentrate that mess so it's relevant to RNA or the origin of life — it's all in the eye of the beholder. And almost all of prebiotic chemistry is like this; they take chemicals of their own selection.
People were talking about Steve Benner and his borate paper where he selected, of his own free will, the chemical formaldehyde, the chemical acid-aldehyde, and the mineral borate, and he decided to mix them together and got a product that he himself said was significant in leading to the origin of RNA world, and I, looking at the same thing, see only the hands of Steve Benner reaching to the shelf of organic chemicals, picking formaldehyde, and from another shelf, picking acidaldehyde, etc. Excluding them carefully. Picking a mineral which occurs only in selective places on the Earth and putting it in in heavy doses. And at the end getting a complex of ribose and borate, which by itself would be of no use for making RNA, because the borate loves to hold onto the ribose, and as long as it holds onto the ribose it can't be used to make RNA. If it lets go of the ribose, then the ribose becomes vulnerable to destruction by all the other environmental agents. The half-life of pure ribose in solution, a different experiment and a very good one, by Stanley Miller is of the order of one or two hours, and all of the other sugars prominent in Earth biology have similar instability.
I was publishing papers like this and I got the reputation, or the nickname in the laboratory of the prebiotic chemist, of 'Dr. No'. If someone wanted a paper murdered, send it to me as a referee. And so on. At some point, someone said, Shapiro, you've got to be positive somewhere. So how did life start? And do we have any examples of authentic abiotic chemistry, not subject to investigator interference? The only true samples we have are those meteorites, which are scooped up quickly and often fallen in an unspoiled place — there was a famous meteorite that fell in France in a sheep field in the 1840s and led to dreadful chemistry of people seeing all sorts of bio molecules in it, not surprisingly. But if you took pristine meteorites and look inside, what you see are a predominance of simple organic compounds. The smaller the organic compound, the more likely it is to be present. The larger it is, the less likely it is to be present. Amino acids, yes, but the simplest ones. Over a hundred of them. All the simplest ones, some of which, coincidentally, overlap the unique set of 20 that coincide with Earth life, but not
containing the larger amino acids that overlap with Earth life. And no sample of a nucleotide, the building block of RNA or DNA, has ever been discovered in a natural source apart from Earth life. Or even take off the phosphate, one of the three parts, and no nucleoside has ever been put together. Nature has no inclination whatsoever to build nucleosides or nucleotides that we can detect, and the pharmaceutical industry has discovered this.
Life had to start with the mess — a miscellaneous mixture of organic chemistry to begin with. How do you organize this? You have to have a preponderance of some chemicals or lacking others would be against the second law of thermo-dynamics — it violates a concept that as a non-physicist that I barely grasp called 'entropy'.
In the simplest case, and there may be many more elaborate cases, they found that the energy wouldn't be released unless some chemical transformations took place. If the chemical transformations took place then the energy was released, a lot of it is heat. If this just went on continuously, all you do is use up the energy. Release all of it and you've converted one chemical to another. Big deal. To get things interesting, you have to close the cycle where the chemicals can be recycled by processes of their own, and then go through it again, releasing more energy. And once you have that, you can then develop nodes — because organic chemistry is very robust, there are reaction pathways leading everywhere, which is why it's such a mess.
One doesn't need a freak set of perhaps a hundred consecutive reactions that will be needed to make an RNA, and life becomes a probable thing that can be generated through the action of the laws of chemistry and physics, provided certain conditions are met. You must have the energy. It's good to have some container or compartment, because if your products just diffuse away from each other and get lost and cease to react with one another you'll eventually extinguish the cycle. You need a compartment, you need a source of energy, you need to couple the energy to the chemistry involved, and you need a sufficiently rich chemistry to allow for this network of pathways to establish itself. Having been given this, you can then start to get evolution.
https://jsomers.net/life.pdf

Michael Polanyi: “Life’s Irreducible Structure,” published in the journal Science in 1968:
“Suppose that the actual structure of a DNA molecule were due to the fact that the bindings of its bases were much stronger than the bindings would be for any other distribution of bases, then such a DNA molecule would have no information content. Its code-like character would be effaced by an overwhelming redundancy. […] Whatever may be the origin of a DNA configuration, it can function as a code only if its order is not due to the forces of potential energy. It must be as physically indeterminate as the sequence of words is on a printed page.”
To understand why random events are not a good explanation, we best have a look at the deepest level, on an atomic scale. Life uses just five nucleobases to make DNA and RNA. Two purines, and three pyrimidines. Purines use two rings with nine atoms, pyrimidines use just one ring with six atoms. Hydrogen bonding between purine and pyrimidine bases is fundamental to the biological functions of nucleic acids, as in the formation of the double-helix structure of DNA. This bonding depends on the selection of the right atoms in the ring structure. Pyrimidine rings consist of six atoms: 4 carbon atoms and 2 nitrogen atoms. Purines have nine atoms forming the ring: 5 carbon atoms and 4 nitrogen atoms.
Remarkably, it is the composition of these atoms that permit that the strength of the hydrogen bond that permits to join the two DNA strands and form Watson–Crick base-pairing, and well-known DNA ladder. Neither transcription nor translation of the messages encoded in RNA and DNA would be possible if the strength of the bonds had different values. Hence, life, as we understand it today, would not have arisen.
Now, someone could say, that there could be no different composition, and physical constraints and necessity could eventually permit only this specific order and arrangement of the atoms. Now, in a recent science paper from 2019, Scientists explored how many different chemical arrangements of the atoms to make these nucleobases would be possible. Surprisingly, they found well over a million variants. The remarkable thing is, among the incredible variety of organisms on Earth, these two molecules are essentially the only ones used in life. Why? Are these the only nucleotides that could perform the function of information storage? If not, are they perhaps the best? One might expect that molecules with smaller connected Carbon components should be easier for abiotic chemistry to explore.
According to their scientific analysis, the natural ribosides and deoxyribosides inhabit a fairly redundant ( in other words, superfluous, unnecessary, needless, and nonminimal region of this space. This is a remarkable find and implicitly leads to design. There would be no reason why random events would generate complex, rather than simple, and minimal carbon arrangements. Nor is there physical necessity that says that the composition should be so. This is evidence that a directing intelligent agency is the most plausible explanation. The chemistry space is far too vast to select by chance the right finely-tuned functional life-bearing arrangement.
In the mentioned paper, the investigators asked if other, perhaps equally good, or even better genetic systems would be possible. Their chemical experimentations and studies concluded that the answer is no. Many nearly as good, some equally good, and a few stronger base-pairing analog systems are known. There is no reason why these structures could or would have emerged in this functional complex configuration by random trial and error. There is a complete lack of scientific-materialistic explanations despite decades of attempts to solve the riddle.
What we can see is, that direct intervention, a creative force, the activity of an intelligent agency, a powerful creator, is capable to have the intention and implement the right arrangement of every single atom into functional structures and molecules in a repetitive manner, in the case of DNA, at least 500 thousand nucleotides to store the information to kick-start life, exclusively with four bases, to produce a storage device that uses a genetic code, to store functional, instructional, complex information, functional amino acids, and phospholipids to make membranes, and ultimately, life. Lucky accidents, the spontaneous self-organization by unguided coincidental events, that drove atoms into self-organization in an orderly manner without external direction, chemical non-biological are incapable and unspecific to arrange atoms into the right order to produce the four classes of building blocks, used in all life forms.
https://sci-hub.ren/10.1126/science.160.3834.1308
David Denton stated:
We now know not only of the existence of a break between the living and non-living world but also that it represents the most dramatic and fundamental of all the discontinuities of nature. Between a living cell and the most highly ordered non-biological systems, such as a crystal or a snowflake, there is a chasm as vast and absolute as it is possible to conceive.
And Lynn Margulis stated: To go from a bacterium to people is less of a step than to go from a mixture of amino acids to a bacterium.
And Eugene Koonin advisory editorial board of Trends in Genetics stated:
A succession of exceedingly unlikely steps is essential for the origin of life, from the synthesis and accumulation of nucleotides to the origin of translation; through the multiplication of probabilities, these make the final outcome seem almost like a miracle. The difficulties remain formidable. For all the effort, we do not currently have coherent and plausible models for the path from simple organic molecules to the first life forms. Most damningly, the powerful mechanisms of biological evolution were not available for all the stages preceding the emergence of replicator systems. Given all these major difficulties, it appears prudent to seriously consider radical alternatives for the origin of life. "
And in fact, there are basically just two options to consider: Either life emerged by a lucky accident, spontaneously through self-organization by unguided natural events, or through the direct intervention, creative force, and activity of an intelligent designer. Evolution is not a possible explanation, because evolution depends on DNA replication. Many have claimed that physical necessity could have promoted chemical reactions, which eventually resulted in the emergence of life. The problem here however is, that the genetic sequence that specifies the arrangement of proteins can be of any order, there is no constraint by physical needs.
But RNA is also incredibly complex and sensitive, and some experts are skeptical that it could have arisen spontaneously under the harsh conditions of the prebiotic world.
https://www.quantamagazine.org/lifes-first-molecule-was-protein-not-rna-new-model-suggests-20171102/
Life before DNA: The origin and evolution of early archean cells
https://www.researchgate.net/publication/270759507_Life_before_DNA_The_origin_and_evolution_of_early_archean_cells
Signature in the Cell: Chapters 9 and 10
https://sfmatheson.blogspot.com/2010/04/signature-in-cell-chapters-9-and-10.html?fbclid=IwAR2a8Qvj7SpTB5_7mLMqisb671U7Tzk3b_UoVFUbioumc-5rAIMBwe5Cbm4
Rates of decomposition of ribose and other sugars: Implications for chemical evolution
https://pdfs.semanticscholar.org/bfa2/d96d2adb03fa603f5cdac06dd0c922fb76da.pdf?_ga=2.14589559.1378959098.1615340959-1388763040.1615340959
The peptides would have been sticky assemblies of the amino acids that were spontaneously created in the primeval chemical soup; the short peptides would have then bound to one another, over time producing a protein capable of some sort of action. Tawfik, who is in the Institute's Biomolecular Sciences Department, says that is all well and good, "but one vital type of amino acid has been missing from that experiment and every experiment that followed in its wake: amino acids like arginine and lysine that carry a positive electric charge." These amino acids are particularly important to modern proteins, as they interact with DNA and RNA, both of which carry net negative charges. RNA is today presumed to be the original molecule that could both carry information and make copies of itself, so contact with positively-charged amino acids would theoretically be necessary for further steps in the development of living cells to occur.
https://www.sciencedaily.com/releases/2020/06/200622095023.htm
Further readings:
Biochemical fine-tuning - essential for life
https://reasonandscience.catsboard.com/t2591-biochemical-fine-tuning-essential-for-life
Chemical Etiology of Nucleic Acid Structure
http://sci-hub.ren/https://science.sciencemag.org/content/284/5423/2118
Formation of RNA Phosphodiester Bond by HistidineContaining Dipeptides
http://sci-hub.ren/https://onlinelibrary.wiley.com/doi/full/10.1002/cbic.201200643
Non-enzymatic Polymerization of Nucleic Acids from Monomers: Monomer SelfCondensation and Template-Directed Reactions
http://sci-hub.ren/https://www.eurekaselect.com/104564/article
New Twist Found in the Story of Life’s Start
https://www.quantamagazine.org/chiral-key-found-to-origin-of-life-20141126/
Chiral selection in poly(C)-directed synthesis of oligo(G)
http://sci-hub.ren/https://www.nature.com/articles/310602a0
Origins of building blocks of life: A review
https://www.sciencedirect.com/science/article/pii/S1674987117301305
Spontaneous formation and base pairing of plausible prebiotic nucleotides in water
https://www.nature.com/articles/ncomms11328
Ribose and related sugars from ultraviolet irradiation of interstellar ice analogs
http://sci-hub.ren/https://science.sciencemag.org/content/352/6282/208
Phosphodiester bond
https://en.wikipedia.org/wiki/Phosphodiester_bond
DNA & RNA: The foundation of life on Earth
http://xaktly.com/NucleicAcids.html
Life as a guide to prebiotic nucleotide synthesis
https://www.nature.com/articles/s41467-018-07220-y
The Quote Mine Project
http://www.talkorigins.org/faqs/quotes/mine/part2.html
Studies on the origin of life — the end of the beginning
http://sci-hub.ren/https://www.nature.com/articles/s41570-016-0012
The cosmological model of eternal inflation and the transition from chance to biological evolution in the history of life
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892545/
Prebiotic Systems Chemistry: Complexity Overcoming Clutter
https://www.cell.com/chem/fulltext/S2451-9294(17)30087-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2451929417300876%3Fshowall%3Dtrue
Miller-Urey and Beyond: What Have We Learned About Prebiotic Organic Synthesis Reactions in the Past 60 Years?
http://sci-hub.ren/https://www.annualreviews.org/doi/abs/10.1146/annurev-earth-040610-133457
A Natural Origin-of-Life: Every Hypothetical Step Appears Thwarted by Abiogenetic Randomization
This is truly a top notch research paper on abiogenesis, where the authors deal with honesty about the problems, without sugar coat it with evolutionary nonsense vocabulary. They go straight to the facts, expose the problems, and provide a honest conclusion.
https://osf.io/p5nw3/
Paradoxes in the origin of life
http://sci-hub.ren/https://www.ncbi.nlm.nih.gov/pubmed/25608919
Studies on the origin of life the end of the beginning
http://sci-hub.ren/https://www.nature.com/articles/s41570-016-0012
Ring Structure for Ribose:
http://chemistry.elmhurst.edu/vchembook/543ribose.html
https://chem.libretexts.org/Bookshelves/Biological_Chemistry/Supplemental_Modules_(Biological_Chemistry)/Carbohydrates/Monosaccharides/Ribose
Ribonucleotides
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845210/
Exploring the Emergence of RNA Nucleosides and Nucleotides on the Early Earth
https://www.mdpi.com/2075-1729/8/4/57/htm
Evolutionist criticisms of the RNA World conjecture
https://creation.com/cairns-smith-detailed-criticisms-of-the-rna-world-hypothesis
Prebiotic chemistry and the origin of the RNA world.
http://sci-hub.ren/https://www.ncbi.nlm.nih.gov/pubmed/15217990
Robert Shapiro: A Simpler Origin for Life February 12, 2007
https://www.scientificamerican.com/article/a-simpler-origin-for-life/?fbclid=IwAR0oMG32MWATWqtqg96hC-V4MEDAQAbW6oBcg_c_FNLxAUsmX8szZja5Mo8
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