DOI:10.1002/chem.201803889 Review & Prebiotic Chemistry AUniversalGeochemical Scenario for Formamide Condensation and Prebiotic Chemistry Raffaele Saladino,*[a] Ernesto Di Mauro,[a] and Juan Manuel García-Ruiz*[b] Chem. Eur.J.2019, 25,3181 –3189 3181 2019 The Authors. Published by Wiley-VCH Verlag GmbH &Co. KGaA, Weinheim Review Abstract: The condensation of formamide has been shown tures forming under alkaline silica-rich solutions are excellent to be arobust chemical pathway affording molecules neces- catalysts for the condensation of formamide with respect to sary for the origin of life. It has been experimentally demon- other minerals. We also propose thatthese structures were strated that condensation reactions of formamide are cata- likely forming as earlyas4.4 billion years ago when the lyzed by anumber of minerals, including silicates, phos- whole earth surface was areactor,aglobalscale factory, re- phates, sulfides, zirconia, and borates, and by cosmicdusts leasing large amounts of organiccompounds. Our experi- and meteorites. However,acritical discussion of the catalytic mental resultssuggestthat the conditions required for the power of the tested minerals, and the geochemical condi- synthesis of the molecular bricks from which life self-assem- tions under whichthe condensation would occur,isstill bles, rather than being local and bizarre, appears to be uni- missing. We show here that mineralself-assembled struc- versal and geologically rather conventional. 1. Introduction marizedbythe aphorism:“metabolism-first or genetics-first?”) might thus consist on thepresence and on the productivein- Origin of life lacks at present an uncontroversial scenario and teractions of elements of both pre-genetics and pre-metabo- unequivocal chemical and physical–chemical frames of refer- lism. It is difficult to imagine that metabolic processes of any ence. Recent progress, however,allow some mote of opti- level of complexitycould develop and evolve in the absence mism. of aform of information transmission and that information- Life is arobust phenomenon. These considerations suggest containing molecules could form and replicate in the absence that its first chemicalsteps must have been as robust and effi- of some form of energy harnessing and control. Hence the ne- cient. Indications that the core chemical frame of the early pro- cessity for prebiotically fertile syntheses to be as rich and varie- cesses was centered on the properties of hydrogen cyanide gate as possible, necessarily affording compounds of different HCN and, more diffusely and more abundantly,onthose of its type and purport. hydrolyzed but still highly reactive derivativeformamide Given the elemental compositionofbiological molecules, NH2COH have been collected during the last twenty years. largely consisting of H, O, Cand Natoms,the starting com- Here we discuss recent experimental evidences that the geo- pound(s) should reflect such composition. One-carbon atom chemicalprocesses of the early earth provided the necessary, compounds as formaldehyde, formic acid, hydrogen cyanide, efficient, and selectivecatalytic setupfor the transition from and formamide abound in circum-and interstellar space.[1–6] one-carbon atom compounds to nucleic bases,amino acids, Thus, the conditions under which these syntheses may occur sugars,and carboxylic acids. The processeswhich were at the are multiform and potentially diffused at universal scale.[7–13] basis of the geochemical evolutionofthis planetprovided at Reactions from these compounds leadingtohigher chemical the same time the niche for the formation and the environ- complexity occur under avariety of energy sources, of differ- ment for the evolutionofbiogenic compounds. ent chemical mixtures, of catalysts, and of varying physical- Biogenicprocesses were necessarily preceded by the forma- chemicalconditions.[14] tion of prebiotic compounds.Occamian logic (“the simplest is The logic for individuation of potentially biogenic com- the likeliest”) suggests that the conditions in which these earli- pounds works top-down: amolecule or aprocess is prebiotic est processes occurred were not rare, occasional, exotic, or fas- and biogenic if it is aposterioripossible to recognize its bio- tidious. The solutiontothe bias of the origin of the prebiotic logical role or relevance. In this respect, HCN andNH2COH compounds and to the start of their fertile interactions (sum- have shown their worth. HCN and NH2COH chemistries are re- lated,[15–17] as predicted and shown by an in-depth computa- tional study of the formationand decomposition reaction [a] Prof. R. Saladino, Prof. E. Di Mauro channels of NH COH by meansofabinitio molecular dynamics, Dipartimento di Scienze Ecologiche eBiologiche 2 Università della Tuscia,Via San Camillo De Lellis, 01100 Viterbo (Italy) allowing the study of reactions both in gas and in liquid [18] E-mail:[email protected] phase. This analysishas shown asimilarstabilityofNH2COH [b] Prof. J. M. García-Ruiz and HCN in solution as well as their relatively facile intercon- Laboratorio de Estudios Cristalogrµficos [19] version. NH2COH was shown to form in the classical Urey– Instituto Andaluz de Ciencias de la Tierra, CSIC-Universidad de Granada Miller condensation experiment,[7] alongwith formic acid but Av.Delas Palmeras 4, Armilla (Granada) (Spain) E-mail:[email protected] not with HCN. Formamide has in particular shown its versatili- [20] Supporting information and the ORCID identification number(s) for the ty owing to the mentioned ubiquity and to its facile forma- author(s) of this articlecan be found under: tion and possibility of concentration.[21,22] https://doi.org/10.1002/chem.201803889. The geochemicalscenario taken into consideration has been 2018 The Authors. Published by Wiley-VCH Verlag GmbH&Co. KGaA. chosen based on its geochemicallikelihood and its evidence- This is an open access article under the terms of Creative Commons Attri- based consistence. This scenario has been experimentally chal- bution NonCommercialLicense, whichpermitsuse, distributionand repro- duction in any medium, provided the original work is properlycited and is lengedwith NH2COH synthetic properties (as described below), not used for commercial purposes. because of its widespread presence andthe experimentally ob- Chem. Eur.J.2019, 25,3181 –3189 www.chemeurj.org 3182 2019 The Authors. Published by Wiley-VCH Verlag GmbH &Co. KGaA, Weinheim Review served flexibility of its chemistry.This approach does not ex- biotic mixture is usually richinproductsirrespective of the clude the eventual integration with the possible contribution nature of the specific mineral present during the condensation. of other reactants as HCN and/orHCOOH. However, one On the other hand, some selectivityoccurs dependingonthe should consider that the more complex is the prebiotic reac- mineralogical origin and elemental composition of the catalyst. tion mixture, the higheristhe possibility of encounteringthe For example, in the silicatefamily the synthesis of pyrimidine “asphalt problem”, as pointed out by S. Bennerand co-au- nucleobases is enhanced by the presence of either magnesium thors.[23] and iron (Table 1, entries 7–9).[28] In the case of sulfur-contain- We report in Part 2, Figure 1, the biologically mostrepresen- ing minerals, sulfur–copper–iron minerals are generally more tative compoundsthat are obtained by reactingNH2CHO in active than simple pyrite and pyrrhotine, pyrite being more ef- the presence of various minerals, as fueled by differentenergy fectivethan pyrrhotine (Table 1, entries 10–17).[29] Again, in the sources. Among the variousclassifications possible, the com- case of borates,the so called hydrates containing hydroxyl pounds obtained are listed as afunctionofthe role that they groups (group A, Dana’s classification), and anhydrous borates assume in biological systems(i.e.,nucleic bases, amino acids, (groupB,Dana’s classification), are more efficient in the forma- carboxylic acids, sugars, etc.), rather than more formal chemical tion of nucleobases than borosilicatesand borocarbonates [30] principles (for example, chemical composition;number of (Table 1, entries 22–29). Finally,the NH2CHO condensation carbon atoms, etc.). works well also in the presence of water,thermalwater being The result of this series of syntheses boils down to the con- areaction medium better than sea water when the condensa- sideration that NH2CHO yields mixtures of prebiotic relevant tion is performed in the presence of the same type of miner- compounds in every energy and catalyst combinationtested. Thus, in order to understand the scenariothat allowed the bio- genic processes on this planet, the question becomes:are the geochemical conditions that bona fide characterizedthe earli- RaffaeleSaladino is President of the Italian est times of this planetcompatible with the production of bio- Society of Astrobiology. He obtained aMaster genic molecules?The answer to this question is positive, as degree in Chemistry at University “Sapienza’’ described in Part 3. (Rome, Italy), and aPh.D. in Chemical Scien- ces at the same University.After post-doctoral training at the University of Montreal 2. The Effect of Minerals on Formamide (Canada)and teaching and researchposition at the University of Tuscia, Viterbo (Italy), he is Condensation now Full Professor in Organic Chemistry at Mineralsplay akey role in the condensation of NH CHO. In the the same University. He is involved in studies 2 on prebiotic chemistry,green catalysis and ox- absence of minerals,