Selective Phosphorylation of RNA‐ and DNA‐Nucleosides under Prebiotically Plausible Conditions

Bechtel, Maximilian; Hümmer, Eva; Trapp, Oliver

doi:10.1002/syst.202200020

Cited by 5 publications

(7 citation statements)

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Section: Resultsmentioning

confidence: 99%

“…5′-Phosphates of ribonucleosides are of interest due to their central role in extant biochemistry, and there have been efforts to bias prebiotic phosphorylation using an orthophosphate toward the 5′-position. 39 The DAP chemistry with ribonucleosides, described so far, has led to selective 2′,3′-cyclic phosphates and little 5′-phosphates. Therefore, it became essential to know whether DAP chemistry is innately restricted in its capacity for generating 5′-phosphorylation of ribonucleosides due to the presence of 2′,3′-cis diols.…”

Section: ■ Resultsmentioning

confidence: 99%

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Enhancing Prebiotic Phosphorylation and Modulating the Regioselectivity of Nucleosides with Diamidophosphate

Cruz,

Jiménez,

Krishnamurthy

2023

J. Am. Chem. Soc.

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Among the many prebiotic phosphorylation chemistries investigated, diamidophosphate (DAP) has shown promising potential for nucleoside phosphorylation. Herein, we show that DAP's phosphorylation capability is enhanced significantly (up to 90%) in wet−dry cycles by a range of prebiotically plausible pHs (6−10) and temperatures (up to 80 °C) in the presence of additives such as formamide, cyanamide, urea, guanidine, 2-aminoimidazole, and hydantoin. For ribonucleosides, the main products are the 2′,3′-cyclic phosphates along with the corresponding 2′-and 3′phosphates, while deoxyribonucleosides form 5′-and 3′-phosphates, the ratios of which are affected by cycles and the presence and nature of the additives. A simple change of temperature to 80 °C with additives leads to higher conversion yields (≈80−90%) with an increased level of 5′-phosphorylation (≈40−49%). This demonstration of enhancing and controlling the regioselectivity of DAP-mediated phosphorylation by a range of additives and conditions potentiates transitioning to the search for more efficient catalysts, enabling regiospecific phosphorylations and oligonucleotide formation in the same milieu and setting.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Resultsmentioning

confidence: 99%

Enhancing Prebiotic Phosphorylation and Modulating the Regioselectivity of Nucleosides with Diamidophosphate

Cruz,

Jiménez,

Krishnamurthy

2023

J. Am. Chem. Soc.

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“… Selective Phosphorylation of RNA- and DNA-Nucleosides under Prebiotically Plausible ConditionsBechtelM.HümmerE.TrappO. Bechtel, M. Hümmer, E. Trapp, O. ChemSystemsChem.20224e202200020 …”

Section: Key Referencesmentioning

confidence: 99%

“…Selectivity toward 5′-AMP could be observed for all reaction conditions investigated. When phosphate buffer was used instead of ultrapure water, no formation of cAMP could be detected by Orbitrap MS or UHPLC-QTOF MS. Reproduced with permission from ref . Copyright 2022 Wiley-VCH.…”

Section: Phosphorylation With Imidazolidine-4-thione Phosphate Under ...mentioning

confidence: 99%

(Photoredox) Organocatalysis in the Emergence of Life: Discovery, Applications, and Molecular Evolution

Bechtel,

Ebeling,

Huber

et al. 2023

Acc. Chem. Res.

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Conspectus Life as we know it is built on complex and perfectly interlocking processes that have evolved over millions of years through evolutionary optimization processes. The emergence of life from nonliving matter and the evolution of such highly efficient systems therefore constitute an enormous synthetic and systems chemistry challenge. Advances in supramolecular and systems chemistry are opening new perspectives that provide insights into living and self-sustaining reaction networks as precursors for life. However, the ab initio synthesis of such a system requires the possibility of autonomous optimization of catalytic properties and, consequently, of an evolutionary system at the molecular level. In this Account, we present our discovery of the formation of substituted imidazolidine-4-thiones (photoredox) organocatalysts from simple prebiotic building blocks such as aldehydes and ketones under Strecker reaction conditions with ammonia and cyanides in the presence of hydrogen sulfide. The necessary aldehydes are formed from CO2 and hydrogen under prebiotically plausible meteoritic or volcanic iron-particle catalysis in the atmosphere of the early Earth. Remarkably, the investigated imidazolidine-4-thiones undergo spontaneous resolution by conglomerate crystallization, opening a pathway for symmetry breaking, chiral amplification, and enantioselective organocatalysis. These imidazolidine-4-thiones enable α-alkylations of aldehydes and ketones by photoredox organocatalysis. Therefore, these photoredox organocatalysts are able to modify their aldehyde building blocks, which leads in an evolutionary process to mutated second-generation and third-generation catalysts. In our experimental studies, we found that this mutation can occur not only by new formation of the imidazolidine core structure of the catalyst from modified aldehyde building blocks or by continuous supply from a pool of available building blocks but also by a dynamic exchange of the carbonyl moiety in ring position 2 of the imidazolidine moiety. Remarkably, it can be shown that by incorporating aldehyde building blocks from their environment, the imidazolidine-4-thiones are able to change and adapt to altering environmental conditions without undergoing the entire formation process. The selection of the mutated catalysts is then based on the different catalytic activities in the modification of the aldehyde building blocks and on the catalysis of subsequent processes that can lead to the formation of molecular reaction networks as progenitors for cellular processes. We were able to show that these imidazolidine-4-thiones not only enable α-alkylations but also facilitate other important transformations, such as the selective phosphorylation of nucleosides to nucleotides as a key step leading to the oligomerization to RNA and DNA. It can therefore be expected that evolutionary processes have already taken place on a small molecular level and have thus developed chemical tools that change over time, representing a hidden layer on the path to enzyma...

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“…Nonenzymatic phosphorylation of ribonucleoside mono- or diphosphates at the 5′-position has been reported. , The existing examples described within the context of prebiotic chemistry were carried out in the absence of water using wet–dry cycles, in the presence of an activating agent, , or were limited to adenosine derivatives . The sources of activated phosphate used were acetyl phosphate, imidazole phosphate, diamidophosphate, and other simple phosphorylating agents. ,− Among these, only acetyl phosphate (AcP) is of direct biological significance. It is a conserved phosphorylating agent in some modern organisms and is regarded by many as the fulcrum between thioester and phosphate metabolism in bacteria and archaea. − Although these studies might give insight into prebiotic phosphorylation, they do not shed light on why ATP became the universal energy currency as none of the elements of ATP are involved.…”

Section: Introductionmentioning

confidence: 99%

Metal/ADP Complexes Promote Phosphorylation of Ribonucleotides

Werner,

Pinna,

Mayer

et al. 2023

J. Am. Chem. Soc.

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Selective Phosphorylation of RNA‐ and DNA‐Nucleosides under Prebiotically Plausible Conditions

Cited by 5 publications

References 40 publications

Enhancing Prebiotic Phosphorylation and Modulating the Regioselectivity of Nucleosides with Diamidophosphate

Enhancing Prebiotic Phosphorylation and Modulating the Regioselectivity of Nucleosides with Diamidophosphate

(Photoredox) Organocatalysis in the Emergence of Life: Discovery, Applications, and Molecular Evolution

Metal/ADP Complexes Promote Phosphorylation of Ribonucleotides

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