Literatura científica selecionada sobre o tema "Prebiotic catalysis"

AbstractTwo sulfur-containing amino acids are included in the list of the 20 classical protein amino acids. A methionine residue is introduced at the start of the synthesis of all current proteins. Cysteine, thanks to its thiol function, plays an essential role in a very large number of catalytic sites. Here we present what is known about the prebiotic synthesis of these two amino acids and homocysteine, and we discuss their introduction into primitive peptides and more elaborate proteins.1 Introduction2 Sulfur Sources3 Prebiotic Synthesis of Cysteine4 Prebiotic Synthesis of Methionine5 Homocysteine and Its Thiolactone6 Methionine and Cystine in Proteins7 Prebiotic Scenarios Using Sulfur Amino Acids8 Introduction of Cys and Met in the Genetic Code9 Conclusion

Modern technology has perfected the synthesis of catalysts such as zeolites and mesoporous silicas using organic structure directing agents (SDA) and their industrial use to catalyze a large variety of organic reactions within their pores. We suggest that early in prebiotic evolution, synergistic interplay arose between organic species in aqueous solution and silica formed from rocks by dynamic dissolution–recrystallization. The natural organics, for example, amino acids, small peptides, and fatty acids, acted as SDA for assembly of functional porous silica structures that induced further polymerization of amino acids and peptides, as well as other organic reactions. Positive feedback between synthesis and catalysis in the silica–organic system may have accelerated the early stages of abiotic evolution by increasing the formation of polymerized species.

Since late 1990s, organocatalysis has been widely explored in many aspects and achieved various difficult transformations. In this field, carbonyl catalysis, which could be traced back to 1860 has been developed with impressive progress including asymmetric variants. Over the years, major activation modes were developed for carbonyl catalysis including exploiting temporary intramolecularity to form catalytic tethers and transient intramolecular nucleophiles, dioxirane formation and imine formation. On the other hand, electrophilic activation is also an important area of organocatalysis where impressive progress has been achieved. However, limited examples were reported to achieve the electrophilic activation via carbonyl catalysis. Organophosphorus compounds are crucially important in many aspects in organic chemistry. Many approaches were developed for asymmetric organophosphorus compounds. In this work, different types of organophosphorus compounds were used as the substances for aldehyde-catalyzed hydrolysis reactions. The first part of this thesis illustrated the strategy to combine carbonyl catalysis and electrophilic activation. The hydrolysis of organophosphorus compounds containing P(=O)-N bond were investigated based on Jencks and Gilchrist’s preliminary results with formaldehyde as the catalyst to promote the hydrolysis of one inorganic substance, phosphoramidate. This Chapter describes a systematic research to identify a superior catalyst, o-phthalaldehyde, and develop catalytic hydrolyses of various organophosphorus compounds containing P(=O)-NHR subunits. Gratifyingly, the reaction proved efficient with phosphinic amides and phosphoramidates. Moreover, chemoselectivity was also studied and selective hydrolysis of the P(=O)-N bonds in the presence of P(=O)-OR bonds could be accomplished. The second part of this thesis demonstrated the further development of one of the major modes of carbonyl catalysis. Formaldehyde was identified as the efficient catalyst to react with α-amino phosphonates to form the transient intramolecular nucleophile, which facilitated the subsequent hydrolysis reactions. In this Chapter, different primary and secondary α-amino phosphonates with phenol as the leaving group, were tested in the reaction conditions. As a result, a vast of mono esters of α-amino phosphoric acids could be formed as the products. Finally, the last portion of this thesis applied the methodologies developed in Chapter 2 to prebiotic chemistry. A prebiotic-related aldehyde, glycolaldehyde was studied as the catalyst for the hydrolysis of organophosphorus compounds containing P(=O)-N bond, including phosphinic amides and phosphoramidates. Additionally, other prebiotic important substances, diamidophosphate (DAP) and monoamidophosphate (MAP) were also investigated for potential glycolaldehyde-catalyzed phosphorylation reaction under aqueous conditions. In the presence of catalytic amount of glycolaldehyde, 1) when water was used as the nucleophile, the hydrolysis of DAP and MAP were significantly improved; 2) when other phosphate nucleophiles were added to compete with water, DAP could act as a phosphorylating reagent to phosphorylate other phosphate nucleophiles. Overall, the results presented in this thesis investigated two different activation modes, electrophilic activation and transient intramolecular nucleophiles, for carbonyl catalysis to hydrolyze different organophosphorus compounds, phosphinic amides, phosphoramidates and α-amino phosphonates. The application of carbonyl catalysis to prebiotic chemistry was also achieved especially with the phosphorylation reaction with DAP.

La catalyse, permettant une réactivité sélective et accrue, est exploitée aussi bien en chimie de synthèse qu’en biologie. Cette thèse l’abordera à deux temporalités différentes. Dans un premier temps, les processus chimiques aux origines de la vie seront étudiés au travers de deux types de catalyse non enzymatique : la catalyse par les métaux rares et la cocatalyse métal/coenzyme. Cette dernière serait un produit de l’évolution pour s’affranchir d’environnements rares et permettre à la chimie prébiotique de se propager vers des milieux communs. Dans un deuxième temps, la catalyse métallique moderne sera discutée. Une nouvelle variante azotée du réarrangement de Piancatelli sera décrite avec des nucléophiles sulfoximines, permettant d’accéder directement et avec de bons rendements à des 4-sulfoximinocyclopenténones inédites, structures prometteuses pour des applications en chimie médicinale
Catalysis enables selective and enhanced reactivity and is harnessed in both synthetic chemistry and biology. This thesis will discuss this concept at two different time points. Firstly, the chemical processes at the origins of life will be studied through two types of non-enzymatic catalysis: rare metal catalysis and metal/coenzyme cocatalysis. The latter is thought to be a product of evolution to become independent from rare environments and enable prebiotic chemistry to spread to more common media. Secondly, modern metal catalysis will be examined. A new aza-variant of the Piancatelli rearrangement will be described with sulfoximine nucleophiles, giving direct access to unprecedented 4-sulfoximinocyclopentenone scaffolds in good yields. These structures hold promises for applications in drug discovery

Un scénario incontournable aux origines de la vie est celui du « monde ARN ». Pour le valider, il est nécessaire d’expliquer comment les premières molécules d’ARN se sont formées à partir de précurseurs moléculaires plus simples. Reste à savoir si les nucléobases non canoniques ont été formées parallèlement aux canoniques ou plus tard, lorsque la vie a nécessité une plus grande diversité fonctionnelle. Notre hypothèse est que les voies métaboliques modernes pourraient être en partie héritées des réseaux de réactions abiotiques, compatibles avec le contexte géochimique. Ces réseaux seraient le résultat d’une série de réactions établies par l’interaction de molécules organiques avec des minéraux inorganiques. Le rôle catalytique aurait alors été joué par une catalyse hétérogène sur des sites de surface. Les réactions thermodynamiquement défavorables pourraient s’appuyer, sur des surfaces minérales et sur d’autres sources d’énergie libre que les molécules d’ATP : molécules inorganiques de haute énergie ou exploitation de déséquilibres macroscopiques. Afin de tester cette hypothèse, la voie de l’orotate, menant à la synthèse de l’uracile, est étudiée ici pour tester comment les voies protométaboliques se sont développées dans un monde prébiotique exempt d’enzymes et comment le contexte géochimique a affecté les origines de la vie. Le carbamyl phosphate (CP) est le premier synthon à haute énergie à intervenir dans la biosynthèse de l’uridine monophosphate. Nous avons donc étudié la probabilité de sa présence dans des conditions prébiotiques. L’évolution du CP dans l’eau et en solution ammoniacale a été caractérisée à l’aide des spectroscopies ATR-IR, RMN 31P et 13C. A l’ambiante, le CP se transforme en cyanate et en carbamate/hydrogénocarbonate en quelques heures. Le cyanate, moins labile que le CP, demeure un potentiel donneur de carbamyle. En présence d’ammoniac, la décomposition du CP est plus rapide, générant urée et amidophosphates. Nous en concluons que le CP en tant que tel n’est pas un réactif prébiotique probable. Le cyanate et l’urée sont des substituts plus prometteurs que le CP car ils sont riches en énergie et cinétiquement inertes face à l’hydrolyse. Des molécules inorganiques riches en énergie (trimétaphosphate, phosphoramidates) ont également été étudiées pour déterminer si elles pouvaient être sources de carbamyl phosphate. Bien que ces espèces n’aient pas produit de CP, elles ont présenté une transduction d’énergie : la formation de liaisons P-N. Dans la cellule, la deuxième étape de la synthèse des monomères pyrimidiques de l’ARN est la carbamylation de l’aspartate. Nous avons comparé la réaction biosynthétique à deux scénarios sans enzyme : en solution aqueuse et sur minéral imprégné. La synthèse abiotique sur minéral du squelette linéaire de pyrimidine (acide N-carbamylaspartique, NCA) a été effectuée sur une plage thermique allant jusqu’à 250 °C. Bien que l’utilisation de différents donneurs de carbamyle soit conditionnée par la thermodynamique, la cinétique joue un rôle déterminant dans le choix des voies possibles pour la carbamylation de l’acide aspartique. Dans la dernière étape, nous avons exploré en détail la cyclisation du NCA. Nous avons procédé à la caractérisation in situ (ATG, IR) et ex situ (RMN 1H) des précurseurs de la pyrimidine après adsorption et activation thermique sur un large éventail de minéraux. Nos données suggèrent un possible carrefour métabolique pour l’origine chimique des bases canoniques et non canoniques. Nous montrons que les équivalents inorganiques peuvent remplacer l’enzyme effectuant cette étape, mais aussi d’autres membres de sa famille enzymatique (amidohydrolases cycliques) effectuant des réactions de cyclisation. Enfin, les résultats préliminaires évaluent le rôle des conditions redox, sur la base de la chimie du fer, afin de mieux comprendre la formation de l’acide orotique, ainsi que le rôle prépondérant des minéraux dans la réaction formose à l’interface gaz/solide
A promising scenario for the origins of life is that of the «RNA world». To validate this model, it is necessary to explain how the first RNA molecules were born out of simpler molecular precursors. An unsolved question is whether noncanonical nucleobases were formed in parallel to the canonical ones or later, when life required higher functional diversity. Our hypothesis is that modern metabolic pathways could be partly inherited from previously existing abiotic reaction networks, provided they respect the geochemical context. These networks would be the result of a series of reactions established by the interaction of organic molecules with inorganic minerals. The catalytic role, entrusted to enzymes in modern biochemistry, would then have been played by heterogeneous catalysis on specific surface sites. The input of free energy to achieve thermodynamically unfavourable steps could rely on the mineral surfaces, on high energy inorganic molecules, or on macroscopic imbalances.To test this hypothesis in a specific case, the orotate pathway which leads to uracil synthesis, is studied here to test how protometabolic paths developed in an enzyme-free prebiotic world and how geochemical context affected the origins of life. Carbamoyl phosphate (CP) is the first high-energy building block that intervenes in the biosynthesis of uridine monophosphate. Thus, we investigated the likelihood of its occurrence in prebiotic conditions. The evolution of carbamoyl phosphate in water and in aqueous ammonia solutions without enzymes was characterised using ATR-IR, 31P and 13C spectroscopies. Carbamoyl phosphate in water at ambient conditions transforms to cyanate and carbamate/hydrogenocarbonate species within a matter of hours. Cyanate, less labile than CP, remains a potential carbamoylating agent. In ammonia solution, CP decomposition occurs more rapidly and generates urea. We conclude that CP is not a likely prebiotic reagent. Cyanate and urea are more promising substitutes for CP, as they are both “energy-rich” (high free enthalpy molecules in aqueous solutions) and kinetically inert toward hydrolysis. Energy-rich inorganic molecules (trimetaphosphate, phosphoramidates) were also explored for their suitability as sources of carbamoyl phosphate. Although these species did not generate carbamoylating agents, they exhibited energy transduction, specifically the formation of high-energy P–N bonds. In the living cell, the second step of synthesizing pyrimidine RNA monomers is a carbamoyl transfer from a carbamoyl donor to aspartic acid. We compared the biosynthetic reaction to two enzyme-free scenarios: aqueous and dried/wetted mineral. Mineral-assisted abiotic synthesis of the pyrimidine linear skeleton (carbamoyl aspartic acid) was performed over a thermal range from 25 °C up to 250 °C. In addition to aqueous synthesis of pyrimidine nucleobases, which is executed at 25 °C for 16 h, the catalytic properties of silica and hydromagnesite minerals were explored. While the use of various carbamoyl donors is enabled by thermodynamics, kinetics plays a determining role in selecting possible paths for the carbamoylation of aspartic acid as a start for building nucleobases. In the last step we explored in detail the cyclization of N-carbamoyl aspartic acid (NCA). We carried out in situ (TGA, IR) and ex situ (1H NMR) characterization of pyrimidine precursors after adsorption and thermal activation on a wide range of minerals. Our data suggest a possible metabolic crossroad for the chemical origin of canonical and noncanonical bases. We show that inorganic equivalents can replace the enzyme carrying out this synthetic step, but also other members of its enzymatic family (cyclic amidohydrolases). Finally, preliminary results evaluate the role of redox conditions, based on iron chemistry to better understand the orotic acid formation from dihydroorotate, as well as the prominent role of minerals in the formose reaction at the gas/solid interface

Life, as we know it, has emerged from the association of simple building blocks (e.g. HCN, NH3, aldehydes, etc). The reactions required to form the complex subunits of life face a great entropic barrier due to the intermolecular nature of their reactivity. Intermolecular reactions are slow at low concentrations, and therefore, the assembly of complex subunits requires the presence of a concentration mechanism. Formaldehyde, which was present in concentrations as high as 0.02 M, may have been used as a concentration mechanism on early Earth. By tethering two molecules together, formaldehyde allows catalysis via temporary intramolecularity. Moreover, formaldehyde has been shown to act as a hydrolase / hydratase mimic, allowing important rate accelerations in hydration and hydrolysis reactions which are of fundamental importance to prebiotic chemistry. Herein, the efficiency of formaldehyde as a catalyst, operating via temporary intramolecularity is demonstrated for a hydroamination reaction that occurs in dilute aqueous conditions. First, using soluble N-methylallylamine and Nmethylhydroxylamine, formaldehyde allowed catalytic turnover at prebiotically relevant formaldehyde concentrations (0.02 M) for a model hydroamination reaction. The efficiency of formaldehyde was compared to other prebiotic aldehydes, demonstrating that although other prebiotic aldehydes are capable of inducing temporary intramolecularity, they were inferior.A second small molecule which may have played a role in the origin of life is D-glyceraldehyde. Since life’s molecules are homochiral, there is a need to explain how this homochirality arose. There have been many breakthroughs by the scientific community when it comes to addressing this challenge, however there is still no general consensus on the origins of homochirality from a prebiotic perspective. Herein, we demonstrate that D-glyceraldehyde is capable of templating a challenging intermolecular reaction while also transmitting some of its chirality to the product. Though the enantiomeric excess produced was generally low (usually around 20 %), there is a significance behind these results due to prebiotically relevant amplification procedures. Lastly, formaldehyde is examined as a possible desymmetrizing agent; coupled with Brønsted acids, the possibility of formaldehyde to induce desymmetrization of alpha-amino or alpha-hydroxy diesters to produce azlactones, and oxalactones, respectively will be established. Moreover, the use of a chiral Brønsted acid would introduce the ability to achieve this transformation in an enantioselective manner. The resulting azlactones / oxalactones are valuable for two reasons: 1) the lactones are present in bioactive molecules, and 2) the lactones can be hydrolyzed to produce chiral alpha-amino / alpha-hydroxy acids. Therefore, we began a systematic study of the conditions required to allow this transformation to occur. This study indicates that the desymmetrization of an alpha-amino diester is possible, producing moderate yields of the resulting azlactone. The desymmetrization of alpha-hydroxy diesters however proved more challenging, and no conversion was observed. Further investigation is required to the increase efficiency of the desymmetrizations, and experimentation with chiral Brønsted acids is required in order to discover enantioselective transformations.

We present here the hypothesis of a possible relationship between metal atom clusters and the formation of organic molecules in the interstellar medium and on small bodies as a possible pathway to the origin of such molecules. Two distinct stages are díscussed: a) the possible formation and presence of atom clusters in space and on the primitive Earth, and b) the synthesis of interstellar and terrestrial prebiotic organic molecules, a process in which metalclusters could be the active catalysts. The confirmatíon of these suggestions might be very important in arder to explain the presence of extra-terrestrial organic molecules in the interstellar medium, small bodies and planetary systems, and therefore would have great relevance in cosmochemistry and in the current theories about the origins of life.

La matière vivante se caractérise par la présence de biopolymères non aléatoires dont la fonction biologique dépend de la séquence en monomères. Pour comprendre les origines de la vie, il est essentiel d’expliquer l’émergence de polymères non aléatoires dans un monde où les cellules vivantes n’existaient pas. Dans ce travail, des approches analytiques basées essentiellement sur la spectrométrie de masse à ultra haute résolution ont été appliquées à l’analyse globale des produits de réaction issus de l’activation thermique de mélanges d’acides aminés sur surface minérale (silice), dans des conditions compatibles avec un scénario prébiotique. La formation d’oligopeptides relativement longs, avec des stœchiométries non aléatoires, a été montrée. Il apparaît notamment que la formation d’hétéropeptides est privilégiée. Une étude structurale des oligopeptides formés a été menée par spectrométrie de masse en tandem, éventuellement couplée à la chromatographie liquide ou à la mobilité ionique. Elle a permis de mettre en évidence des sélectivités de séquence. En outre, la formation de régioisomères a été démontrée, ce qui signifie que dans nos conditions de polymérisation le scénario ne manifeste pas de régiosélectivité pour les liaisons α prédominantes dans les protéines. Enfin, aucune énantiosélectivité significative n’a été mise en évidence. Par ailleurs, une étude mécanistique de la réaction de condensation a été menée. L’apparition successive d’oligopeptides de plus en plus longs a été observée pour des températures ou des temps de réaction croissants, suggérant des processus de polymérisation par étapes
Living matter is characterized by the presence of non-random biopolymers whose biological function depends on the monomer sequence. Thus, a major challenge for the elucidation of the Origins of Life lies in understanding how non-random polypeptides were formed and selected among all of the possible ones. In this work, analytical approaches based essentially on ultra-high resolution mass spectrometry were applied to the global analysis of desorption mixtures resulting from the thermal activation of amino acids on a mineral surface, under conditions compatible with a prebiotic scenario. The formation of relatively long oligopeptides, with non-random stoichiometries has been shown. It appears that the formation of hetero-peptides is favored. A structural study of the oligopeptides formed was also carried out by tandem mass spectrometry, optionally coupled with liquid chromatography or ion mobility. It made it possible to demonstrate sequence selectivity. Furthermore, the formation of regio-isomers has been demonstrated, confirming that under our polymerization conditions the scenario does not manifest regioselectivity for the predominant α bonds in proteins. Finally, no significant enantioselectivity was demonstrated. In addition, a mechanistic study of the condensation reaction was carried out. The successive appearance of oligopeptides of increased length has been observed over ranges of temperatures or reaction times, suggesting stepwise polymerization processes

碩士
國立中正大學
化學暨生物化學研究所
102
There are two chapters in this thesis. The main topic is the theoretical study of the reaction mechanisms of the prebiotic synthesis of adenine, cytosine and uracil in neutral environment. In addition to the gas-phase study we also applied the microsolvation model and the polarizable continuum model (PCM) to take the solvation effects into consideration . In chapter one, we followed the mechanism proposed by Shapiro for the prebiotic synthesis of cytosine and uracil. Four fundamental steps were modeled computationally in the gas phase and in bulk solvent with and without microsolvation by a small molecule of H2O or NH3. We found that if a reaction involved hydrogen-atom transfer, the small molecule that was used as the microsolvation solvent also played as the role of a catalyst, and it could significantly reduce the energy barriers by approximately 20 kcal/mol. The bulk solvation model could sometimes further lower the barrier by a few kcal/mol. In chapter two, we followed the mechanism proposed by Oró for the prebiotic synthesis of adenine starting from polymerization of HCN. Five fundamental steps were modeled computationally in the gas phase and in bulk solvent with and without microsolvation by one or two small molecules of H2O or NH3. Similar to the study in Chapter one, the microsolvation was found to significantly lower the energy barriers for hydrogen transfer reactions in the mechanism. In summary, the study in this thesis suggested that the prebiotic synthesis of nucleic bases, and perhaps other biomolecules, can be catalyzed by small solvent-like molecules present in prebiotic conditions. This would make the origin of life from early earth with very limited raw material available more likely.

Abstract The study of the origin deals with hypothetical chemical entities and primordial creatures that presumably do not exist today. It focuses on central attributes of the interactions among these primordial entities, that is, the physicochemical reactions of their gradual organization into more and more complex forms in the prebiotic evolution process. The latter encompasses catalysis, template-directed synthesis of oligomers and polymers, mutability, selection, establishment of primordial reaction cycles, compartmentation, and the buildup of complexity, all of which are manifested as evolutionary processes at the molecular level.

After reviewing the results for the Michaelis–Menten enzyme mechanism, both from the usual deterministic coupled differential equations of Chemical Kinetics and from the stochastic model of Gillespie, the first conclusion is that both, the smoothness of the concentration changes from the first model and the chaotic concentration fluctuations from the second model, are implied by the kind of mathematics used. I consider that neither the smoothness nor the chaotic fluctuations of the concentrations are real facts. In the new model developed here, the timeline is a sequence of equally spaced time points, at which concentration changes can occur; the time interval, τ, is to be selected by analyzing the results. The coupled algebraic equations resulting from the linear integration of the differential equations of the first model, instead of being solved, are used to extract the constraints of the Objective Function whose minimization renders the collective optimum values of the concentrations along the reaction path. One advantage of this model is that by adding the conservation of mass as an additional constraint in the Objective Function, a self-organized behavior is observed in this prebiotic system along with the chemical dynamics, which I consider real.

A transition from geochemistry to biochemistry has been considered as a necessary step towards the emergence of primordial life. Nevertheless, how did this transition occur is still elusive. The chemistry underlying this transition is likely not a single event, but involves many levels of creation and reconstruction, finally reaching the molecular, structural, and functional buildup of complexity. Among them, one apparent question is: how the biochemical catalytic system emerged from the mineral-based geochemical system? Inspired by the metal–ligand structures in metalloenzymes, many researchers have proposed that transition metal sulfide minerals could have served as structural analogs of metalloenzymes for catalyzing prebiotic redox conversions. This assumption has been tested and verified to some extent by several studies, which focused on using Earth-abundant transition metal sulfides as catalysts for multi-electron C and N conversions. The progress in this field will be introduced, with a focus on the CO2 fixation and ammonia synthesis from nitrate/nitrite reduction and N2 reduction. Recently developed methods for screening effective mineral catalysts were also reviewed.