Theoretical origin of life: terrible chemistry presented (Introduction)

by David Turell , Sunday, January 15, 2023, 21:54 (467 days ago) @ David Turell

James Tour plus one to the battle lines:

https://inference-review.com/letter/a-storm-in-a-primordial-teacup

"In a recent review, James Tour wrote that Eddy Jiménez et al., in a study on the chemical origins of life, made “bold claims” about the significance of their work.1 Tour claimed that their experimental approach is “unconscionable” and stated that “rather than leading to any sort of chemical model, the research serves only to underscore how this particular approach is unlikely to yield any clues about how life emerged.”

"Tour does not take exception to the chemistry; rather he is scathing about the ramifications of this study for understanding the origin of life. He picks up on five areas he believes are shortcomings that, furthermore, epitomize many studies on the origin of life:

"The inability of the study to explain the prebiotic source of homochiral precursors such as 2′-deoxyribonucleoside.
The high concentrations used in the laboratory studies—that is to say “how might starting materials become available in sufficiently high yields and undiluted by the oceans.”

"The use of a specific precursor, namely DAP, which according to Tour “has become so ubiquitous in origins of life (OOL) research that it is now simply accepted as being prebiotically relevant.”

"The lack of explanation for how the desired reactions managed to occur without competing compounds, which in this case are other nucleophiles.

"The inability to dispose of unwanted and undesirable chemical products—here, a deleterious 2′, 5′-linkage.

Are Tour’s claims valid, or is he on the verge of insanity?

"If Tour is insane, then I will offer to join him at the asylum check-in. I find exactly the same assumptions at play in my own area of research, namely lipids, and in the potential roles that lipids may have played in the origin of life and in the formation of the first protocell. To illustrate the similarities with the issues raised by Tour, I will briefly consider a study published in 2019 by Luping Liu et al., from the laboratory of Neal Devaraj, entitled “Enzyme-Free Synthesis of Natural Phospholipids in Water.”3 The claims made by Devaraj et al. might actually be stronger than those made by Jiménez, inasmuch as Devaraj states, “This high-yielding non-enzymatic synthesis of natural phospholipids in water … sheds light on the origin and evolution of cellular membranes.” All five of the issues raised by Tour can be seen in this study:

"The authors do not consider chirality.

"The study uses high concentrations of precursors, in the millimolar range, without ever discussing how such high concentrations could have been generated prebiotically.

"The study also uses a specific precursor, in this case an acyl thioester, suggested to be “obtained using prebiotically relevant condensing agents such as dicyandiamid.”

"Competing compounds are barely considered.

"The authors essentially ignore the effect of unwanted chemical reactions that might produce products that would interfere with the required reaction.

"it is the “Results and Discussion” section that gives away the game. I can do no better than quote the authors, who state,

"We further attempted to obtain various diacylphospholipids such as phosphatidylethanolamine, phosphatidylserine and phosphatidylglycerol by oleoylating the corresponding lysophospholipids; however, the reactivity of [the] acylation reagent is insufficient for these lysolipids and no considerable yields of the desired diacylphospholipids were achieved.
In other words, the conditions selected for the enzyme-free synthesis of phospholipids only works with one specific lysolipid precursor. But it gets worse. While the authors did not consider the presumably deleterious role of side-products that would have accumulated during the reactions, the addition of other lipids, such as sodium dodecyl sulfate, almost completely inhibited the acylation reaction even using the one lipid precursor that had worked previously—i.e., lysophosphatidylcholine—such that the yield dropped to less than 10%. Presumably, the inclusion of other lipids or chemical side-products would similarly inhibit the transacylation reaction.

***

"Just as the Jiménez et al. paper seems to be much ado about nothing, I would argue, agreeing with Tour, that many similar articles about the origin of life do not actually explain anything. Admittedly, careful choice of conditions, whether realistic or not for prebiotic scenarios, demonstrates that certain reactions and pathways might conceivably occur. But when considering the kind of issues raised by Tour, and raised herein, it might be more realistic, and humble, to tone down widely publicized claims that researchers understand the chemical reactions and pathways that result in the emergence of life."

Comment: any followers of this website know my feelings that the research is awful and over- hyped. I stand fully with this article. Grant committees need their heads examined.