Ernesto Di Mauro

A possible prebiotic synthesis of purine, adenine, cytosine, and 4(3H)-pyrimidinone from formamide: implications for the origin of life.

The synthesis of prebiotic molecules is a major problem in chemical evolution as well as in any origin-of-life theory. We report here a plausible new prebiotic synthesis of naturally occurring purine and pyrimidine derivatives from formamide under catalytic conditions. In the presence of CaCO(3) and different inorganic oxides, namely silica, alumine, kaolin, and zeolite (Y type), neat formamide undergoes the formation of purine, adenine, cytosine, and 4(3H)-pyrimidinone, from acceptable to good yields. The role of catalysts showed to be not limited to the improvement of the yield but it is also relevant in providing a high selectivity in the products distribution.

Guanine, adenine, and hypoxanthine production in UV-irradiated formamide solutions: relaxation of the requirements for prebiotic purine nucleobase formation.

Here, we show for the first time that gua-nine, adenine, and hypoxanthine can be produced from forma-mide in a single model prebiotic reaction at lower tempera-tures than previously reported, if formamide is subjected to UVirradiation during heating; this observation relaxes the require-ments for prebiotic purine nucleobase formation. The yieldand diversity of purines produced in heated/UV-irradiated for-mamide are further enhanced by the presence of inorganiccatalysts, as solids or as dissolved ions. We also analyzed theproducts of formamide solutions to which specific hydrogencyanide (HCN) condensation products

One-Pot TiO2-Catalyzed Synthesis of Nucleic Bases and Acyclonucleosides from Formamide: Implications for the Origin of Life

A novel one‐pot TiO2‐catalyzed synthesis of nucleobases and acyclonucleosides from formamide is reported. Since formamide can be formed under prebiotic conditions, these reactions have implications for the origin of life. While a number of purine derivatives have been found as products of non‐TiO2‐catalyzed reactions, important compounds that would not otherwise occur (namely, thymine, 5hydroxymethyluracil, and acyclonucleosides) are formed in acceptable yields by TiO2‐catalyzed reactions. Moreover, TiO2 selectively affects the rates of degradation of nucleobases, as single units and when embedded in polynucleotides.

Generation of Long RNA Chains in Water

The synthesis of RNA chains from 3′,5′-cAMP and 3′,5′-cGMP was observed. The RNA chains formed in water, at moderate temperatures (40–90 °C), in the absence of enzymes or inorganic catalysts. As determined by RNase analyses, the bonds formed were canonical 3′,5′-phosphodiester bonds. The polymerizations are based on two reactions not previously described: 1) oligomerization of 3′, 5′-cGMP to ∼25-nucleotide-long RNA molecules, and of 3′,5′-cAMP to 4- to 8-nucleotide-long molecules. Oligonucleotide A molecules were further extended by reciprocal terminal ligation to yield RNA molecules up to >120 nucleotides long and 2) chain extension by terminal ligation of newly polymerized products of 3′,5′-cGMP on preformed oligonucleotides. The enzyme- and template-independent synthesis of long oligomers in water from prebiotically affordable precursors approaches the concept of spontaneous generation of (pre)genetic information.

Synthesis and Degradation of Nucleobases and Nucleic Acids by Formamide in the Presence of Montmorillonites

We describe the role of formamide, a product of the hydrolysis of hydrogen cyanide, as precursor of several components of nucleic acids under prebiotic conditions. When formamide is heated in the presence of montmorillonites, the efficient one‐pot synthesis of purine, adenine, cytosine, and uracil is obtained. Along with these nucleobases, several components of the inosine pathway are obtained: 5‐aminoimidazole‐4‐carboxamide, 5‐formamidoimidazole‐4‐carboxamide and hypoxanthine. This almost complete catalogue of nucleic acid precursors is accompanied by N9‐formylpurine, which, containing a masked glycosidic bond in its formyl moiety, is a plausible precursor of purine acyclonucleosides. In addition, montmorillonites differentially affect the rate of degradation of nucleobases when embedded in 2′‐deoxyoligonucleotides; namely, montmorillonites protect adenine and guanine from the degradative action of formamide, while thymine degradation is enhanced. The oligonucleotide backbone reactivity to formamide is also affected; this shows that the interaction with montmorillonites modifies the rate of abstraction of the Hα and Hβ protons on the sugar moieties.

Meteorite-catalyzed syntheses of nucleosides and of other prebiotic compounds from formamide under proton irradiation

Significance Modern research on the origin of life started with Urey–Miller’s 1953 report on the spontaneous formation of amino acids upon application of electric discharge on a model of the pristine Earth atmosphere. Formamide provides a chemically sound starting material for the syntheses of prebiotic compounds; its role in prebiotics is becoming recognized. Kiloparsecs-wide clouds of formamide were observed in the interstellar space. The energy sources for the syntheses explored so far were largely thermal, and the catalysts used were mostly terrestrial. In the presence of meteorites and with high-energy protons, we observe the production of unprecedented panels of nucleobases, sugars, and, most notably, nucleosides. Carboxylic acids and amino acids complete the recipe. These findings extend prebiotic plausible scenarios well beyond our planet. Liquid formamide has been irradiated by high-energy proton beams in the presence of powdered meteorites, and the products of the catalyzed resulting syntheses were analyzed by mass spectrometry. Relative to the controls (no radiation, or no formamide, or no catalyst), an extremely rich, variegate, and prebiotically relevant panel of compounds was observed. The meteorites tested were representative of the four major classes: iron, stony iron, chondrites, and achondrites. The products obtained were amino acids, carboxylic acids, nucleobases, sugars, and, most notably, four nucleosides: cytidine, uridine, adenosine, and thymidine. In accordance with theoretical studies, the detection of HCN oligomers suggests the occurrence of mechanisms based on the generation of radical cyanide species (CN·) for the synthesis of nucleobases. Given that many of the compounds obtained are key components of extant organisms, these observations contribute to outline plausible exogenous high-energy–based prebiotic scenarios and their possible boundary conditions, as discussed.

Synthesis and degradation of nucleic acid components by formamide and iron sulfur minerals

We describe the one-pot synthesis of a large panel of nucleic bases and related compounds from formamide in the presence of iron sulfur and iron-copper sulfur minerals as catalysts. The major products observed are purine, 1H-pyrimidinone, isocytosine, adenine, 2-aminopurine, carbodiimide, urea, and oxalic acid. Isocytosine and 2-aminopurine may recognize natural nucleobases by Watson-Crick and reverse Watson-Crick interactions, thus suggesting novel scenarios for the origin of primordial nucleic acids. Since the major problem in the origin of informational polymers is the instability of their precursors, we also investigate the effects of iron sulfur and iron-copper sulfur minerals on the stability of ribooligonucleotides in formamide and in water. All of the iron sulfur and iron-copper sulfur minerals stimulated degradation of RNA. The relevance of these findings with respect to the origin of informational polymers is discussed.

Hyperacetylation of chromatin at the ADH2 promoter allows Adr1 to bind in repressed conditions

We report that in vivo increased acetylation of the repressed Saccharomyces cerevisiae ADH2 promoter chromatin, as obtained by disrupting the genes for the two deacetylases HDA1 and RPD3, destabilizes the structure of the TATA box‐containing nucleosome. This acetylation‐dependent chromatin remodeling is not sufficient to allow the binding of the TATA box‐binding protein, but facilitates the recruitment of the transcriptional activator Adr1 and induces faster kinetics of mRNA accumulation when the cells are shifted to derepressing conditions.

From formamide to RNA: the roles of formamide and water in the evolution of chemical information

In pursuing the origin of informational polymers, we followed the assumption that their spontaneous formation could only have occurred: (i) if all the components were present at the same site and in the same reaction, and (ii) if the thermodynamics of the processes involved favored a polymerized over a monomeric state of the precursors. A plausible scenario satisfying both assumptions is provided.

Attraction, phasing and neighbour effects of histone octamers on curved DNA

Nucleosome core particles were reconstituted on various DNA fragments containing a Crithidia fasciculata kinetoplast curved tract. The results show that, on curved DNA, nucleosome core particles form six- to sevenfold preferentially, relative to bulk sequences. The preferential deposition occurs at multiple periodic positions, whose distribution reveals a unique rotational setting of DNA with respect to the histone octamer surface and whose average periodicity is 10.26 +/- 0.04. Evidence is provided for a context effect in histone octamer deposition: octamers bound to a segment of curved DNA influence the positions of neighbour octamers. Taken together, the preferential formation of nucleosome core particles and the influence on the localization of neighbouring particles suggest for intrinsically bent sequences the biologically relevant role of organizers of nucleosomal arrays.