A Novel Synthesis of Biomolecular Precursors

To survive, an informational macromolecule must solve the major problem set by its very polymeric nature: instability. This is especially true in prebiotic terms because of the presumed initial absence of protective structures (proteins, lipids, etc.). We have analyzed the stability of the ␤-glycosidic and of the 3-and 5-phosphoester bonds in both deoxy monomers and deoxy oligomers under a large set of conditions. The results show a strong dependence of the relative stability of these bonds on the physico-chemical environment. A set of conditions has been identified in which the stability of polymers becomes comparable with that of the precursor monomers. In certain instances the stability of the 5-phosphoester bond is even higher in the polymer than in the mononucleotide.If life on this planet had an early start as it seems (1-8), several conditions had to be satisfied at the same time: abundance of the starting biogenic materials, formation of precursors based on simple chemical processes, and simultaneous (or quasi so) presence of the building blocks to be used for the assembling of informational molecules. We have observed (Refs. 9 -11 and references therein) that the one-carbon compound formamide is an highly versatile building block for the synthetic processes yielding all the necessary precursor nucleic bases. In terms of its possible role in allowing or favoring the formation of informational nucleic polymers, formamide chemistry also provides a possible solution to the lack of reactivity between ribose/deoxyribose with bases through a formose-like reaction yielding acyclonucleosides (10). The reported activity of formamide as activator of transphosphorylation (see "Discussion") provides additional possible relevance to its role in prebiotic reactions leading to pre-genetic informational polymers. The plausibility of its prebiotic role is related to (i) its presence in interstellar medium, in comets and asteroids (12), hence on early Earth; (ii) the ease of its formation by hydrolysis of HCN and its stability in liquid form over a wide range of temperatures (2.5-210°C), thus favoring its concentration from dilute aqueous solutions; and (iii) the above mentioned catalyst-induced wealth of nucleic precursors.The question arises as to whether the physico-chemical conditions (moderately high temperature and varying concentration of formamide in water) allowing active synthesis and potentially leading to polymerization favor or impair the survival of the polymerized materials. In reconstructing the passage from monomers to the information-bearing polymers that we know at present, two major pieces of the mosaic are markedly missing: the knowledge of the mechanisms leading to the formation of the ␤-glycosidic and of the 3Ј-5Ј phosphodiester bonds and, once the polymer had been formed, the physico-chemical reason(s) leading to its very survival as a polymer. In other words, which is the Darwinian selective advantage that overcame the intrinsically higher instability of the polymeric form?The analysis presented h...

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“…This "equilibration-of-the-pool" hypothesis is presented in Ref. 59 and is discussed in detail in Ref. 61.…”

Section: Discussionmentioning

confidence: 95%

“…9 -11, 37, reviewed in Ref. 59) does not constitute a disadvantage. To the contrary, the synthesis/degradation/resynthesis cycle offers the possibility of forming a dynamically equilibrating pool of precursors whose composition depends on the synthesis/degradation rate of each molecular species and on the catalysts present (59).…”

Section: Discussionmentioning

confidence: 99%

Origin of Informational Polymers

Saladino

Crestini

Busiello

et al. 2005

Journal of Biological Chemistry

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“…The role of formamide as prebiotic precursor of the synthesis of nucleic acid bases has been shown under a variety of conditions. In particular the presence of different inorganic compounds, such as oxides, minerals or cosmic dust analogues, is able to catalyze the formamide condensation that originate, among many compounds, purine and pyrimidine bases, namely, the products of the first primordial steps that might have leaded to the appearance of life as we know it (Yamada et al 1972(Yamada et al , 1975Saladino et al 2003Saladino et al , 2004Saladino et al , 2005.…”

Section: Introductionmentioning

confidence: 99%

An infrared study of pure and ion irradiated frozen formamide

Brucato

Baratta

Strazzulla

2006

A&A

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Context. The chemical evolution of formamide (HCONH 2 ), a molecule of astrobiological interest that has been tentatively identified in interstellar ices and in cometary coma, has been studied in laboratory under simulated astrophysical conditions such as ion irradiation at low temperature. Aims. To evaluate the abundances of formamide observed in space or in laboratory, the integrated absorbances for all the principal IR features of frozen amorphous pure formamide deposited at 20 K were measured. Further evidence that energetic processing of ices occurring in space is extremely relevant both to astrochemistry and to astrobiology has been found, showing that new molecular species are synthesized by ion irradiation at a low temperature. Methods. Pure formamide were deposited at 20 K and IR transmission spectra measured for different ice thicknesses. The ice thickness was derived by looking at the interference pattern (intensity versus time) of a He−Ne laser beam reflected at an angle of 45 deg by the vacuum-film and film-substrate interfaces. Samples of formamide ice were irradiated with 200 keV H + ions and IR spectra recorded at different ion fluences. Results. New molecules were synthesized among which are CO, CO 2 , N 2 O, isocyanic acid (HNCO), and ammonium cyanate (NH 4 + OCN − ). Some of these species remain stable after warming up to room temperature.

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“…51 At around 430K in liquid formamide most of the prebiotic building blocks (i.e. nucleobases, nucleosides) can be synthesized, 7,8,[52][53][54] and, after phosphorylation (Ref. 5 ), they can accumulate in the form of nucleotides.…”

Section: Prebiotic Implicationsmentioning

confidence: 99%

Stability of 2′,3′ and 3′,5′ cyclic nucleotides in formamide and in water: a theoretical insight into the factors controlling the accumulation of nucleic acid building blocks in a prebiotic pool

Cassone

Šponer

Saija

et al. 2017

Phys. Chem. Chem. Phys.

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Synthesis of the first RNAs represents one of the cornerstones of the emergence of life. Recent studies demonstrated powerful scenarios of prebiotic synthesis of cyclic nucleotides in aqueous and formamide environments. This raised a question about their thermodynamic stability, a decisive factor determining their accumulation in the prebiotic pool. Here we performed ab initio molecular dynamics simulations at various temperatures in formamide and water to study the relative stabilities of the 2',3' and 3',5' isomers of cyclic nucleotides. The computations show that in an aqueous environment 2',3' cyclic nucleotides are more stable than their 3',5' counterparts at all temperatures up to the boiling point. In contrast, in formamide higher temperatures favor accumulation of the 3',5' cyclic form, whereas below about 400 K the 2',3' cyclic form becomes more stable. The latter observation is consistent with a formamide-based origin scenario suggesting that 3',5' cyclic nucleotides accumulated at higher temperatures subsequently allowed oligomerization reactions after fast cooling to lower temperatures. A statistical analysis of the geometrical parameters of the solutes indicates that thermodynamics of cyclic nucleotides in aqueous and formamide environments are dictated by the floppiness of the molecules rather than by the ring strain of the cyclic phosphodiester linkages.

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A Novel Synthesis of Biomolecular Precursors

Cited by 44 publications

References 42 publications

Origin of Informational Polymers

Origin of Informational Polymers

An infrared study of pure and ion irradiated frozen formamide

Stability of 2′,3′ and 3′,5′ cyclic nucleotides in formamide and in water: a theoretical insight into the factors controlling the accumulation of nucleic acid building blocks in a prebiotic pool

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