Mechanochemical Prebiotic Peptide Bond Formation**

Abstract

The presence of amino acids on the prebiotic Earth, either stemming from endogenous chemical routes or delivered by meteorites, is consensually accepted. In contrast, prebiotically plausible pathways to achieve peptides from unactivated amino acids are still unclear since most oligomerization approaches rely on thermodynamically disfavored reactions in solution. Alternative hypotheses such as the prebiotic impact scenario postulate that the mechanical impacts from meteorites and geochemical phenomena played an important role in delivering exogenous material to Earth, thus providing the geochemical, mechanical, and thermal conditions to synthesize small prebiotic organic compounds in the absence of bulk liquid media. In this context, here we evaluate the applicability of mechanochemistry by ball milling for peptide bond formation under a prebiotic impact scenario. We found that the combination of mechanical forces and prebiotically plausible and ubiquitous minerals as activators enable the oligomerization of amino acids such as glycine in the absence of bulk water (or solvents) and at ambient temperature. Increasing the mechanochemical reactor's temperature is shown to favor the degree of polymerization concomitantly with the formation of cyclic glycine dimer [cyclo(Gly 2 ) or DKP], a product commonly considered as a dead-end in solution peptide bond formation. However, our study shows that DKP can be mechanochemically activated and used as a source for glycine oligomers. The findings of this research provide alternative mechanochemical routes towards oligopeptides and establish new synthetic approaches for prebiotic chemistry that are not limited by poor diffusion of the reactants, thus complementing the current alternating wetting and drying prebiotic environment strategy. File list (2) download file view on ChemRxiv Peptide paper.pdf (816.75 KiB) download file view on ChemRxiv Peptide paper-SI.pdf (1.79 MiB)

New Signatures of Bio-Molecular Complexity in the Hypervelocity Impact Ejecta of Icy Moon Analogues

“…Thus, the abiotic synthesis of peptides is an important step in the prebi-otic chemistry that led to the emergence of life on the primitive Earth. Various scenarios have been suggested on the synthesis of peptides on the prebiotic Earth, which include synthesis in hydrothermal vents and dehydrating condition under dry and wet cycles [54]; synthesis triggers by activating agents [55,56]; presence of mineral catalysis [57,58], high energy protons and UV irradiation [59,60]; volcanic environment [37] and mechanochemical synthesis [50]. However, long polypeptide chains, as found in the present investigation, has not been reported before.…”

“…Long polypeptide chains up to sequence of twelve amino acids as observed in case of glycine is remarkable and has never been reported before. Previous studies have reported shorter peptides using gas gun experiments [31,32] and ball milling techniques [50] simulating extraterrestrial impacts.…”

Zirconium oxo clusters as discrete molecular catalysts for the direct amide bond formation

“…[22][23][24][25][26][27] Catalytic amide bond formation [28][29][30][31][32][33][34][35][36][37] by direct condensation of non-activated carboxylic acids and amines is among the most relevant reactions enabled by Zr catalysts, [38][39][40][41] given their favorable atom economy compared to the amide coupling reagents, [42][43][44][45][46][47][48] and the ready availability of carboxylic acid and amine substrates. [22][23][24][49][50][51][52] However, recent promising advances in metal catalysts are still challenged by the catalyst overall stability, and its tolerance to the water formed as the reaction by-product. 23,24,[53][54][55][56] On the other hand, we have recently discovered metal oxo cluster based catalysts, namely Zr/Hf-polyoxometalates and Zr-based MOFs, exhibit an unusual robustness, allowing reactions to be conducted under 'open-flask' conditions, without any special measures, additives or water scavenging.…”

Frontiers in Prebiotic Chemistry and Early Earth Environments

“…In most RNA-centric models, the ribosome and protein synthesis are late addenda to proto-biology. An alternative class of models proposes instead that a creative stage of chemical evolution (Yu et al 2016 ; Frenkel-Pinter et al 2019 , 2020 ; Stolar et al 2021 ) merged smoothly with Darwinian processes. In some of these models the ribosome was an early foundation to proto-biology; multiple types of biopolymers, some primarily informational and others primarily catalytic, arose in concert via co-evolution (Lanier et al 2017 ; Frenkel-Pinter et al 2020 ).…”