ARTICLE https://doi.org/10.1038/s42004-020-00387-w OPEN Mineral-mediated carbohydrate synthesis by mechanical forces in a primordial geochemical setting ✉ Maren Haas 1,2, Saskia Lamour 1, Sarah Babette Christ 1 & Oliver Trapp 1,2 1234567890():,; The formation of carbohydrates represents an essential step to provide building blocks and a source of chemical energy in several models for the emergence of life. Formaldehyde, gly- colaldehyde and a basic catalyst are the initial components forming a variety of sugar molecules in the cascade-type multi-step formose reaction. While numerous side reactions and even deterioration can be observed in aqueous media, selective prebiotic sugar formation is feasible in solid-state, mechanochemical reactions and might have occurred in early geochemistry. However, the precise role of different basic catalysts and the influence of the atmospheric conditions in the solid-state formose reaction remain unknown. Here we show, that in a primordial scenario the mechanochemical formose reaction is capable to form monosaccharides with a broad variety of mineral classes as catalysts with only minute amounts of side products such as lactic acid or methanol, independent of the atmospheric conditions. The results give insight into recent findings of formose sugars on meteorites and offer a water-free and robust pathway for monosaccharides independent of the external conditions both for the early Earth or an extra-terrestrial setting. 1 Department of Chemistry and Pharmacy, Ludwig-Maximilians-University, Butenandtstr. 5-13, 81377 Munich, Germany. 2 Max-Planck-Institute for ✉ Astronomy, Königstuhl 17, 69117 Heidelberg, Germany. email: [email protected] COMMUNICATIONS CHEMISTRY | (2020) 3:140 | https://doi.org/10.1038/s42004-020-00387-w | www.nature.com/commschem 1 ARTICLE COMMUNICATIONS CHEMISTRY | https://doi.org/10.1038/s42004-020-00387-w rebiotic chemistry aims to find pathways to important the β-elimination yielding dicarbonyl compounds 11, that organic reactants that are compatible with the harsh can further undergo a 1,2-rearrangement and build up lactic P 16 environmental conditions present on early Earth. Over time acid 12 . these basic organic molecules evolved into a diverse set of The instability of the products under aqueous, alkaline reaction molecules essential for life, metabolism, genetic information and conditions and the deterioration of the products forming inso- compartmentalisation. These biologically relevant molecules luble, undefined polymeric substances constitute the major include amino acids, peptides, lipids, nucleotides and sugars. For drawbacks of this reaction17–19. To prevent this, we previously the latter, one of the plausible reaction pathways next to probed a solvent-free variation of this reaction and observed a Eschenmoser’s glyoxylate scenario is the formose reaction1–3, mechanochemical acceleration and alteration of product forma- which was first discovered by Butlerow in 18614. The formation tion20. Albeit the mechanochemical reaction is slower compared of sugars from formaldehyde is generally catalysed by calcium to the aqueous reaction, it gains from higher selectivity and less hydroxide, but mineral catalysis has also been suggested for decomposition. From a prebiotic chemistry perspective, the prebiotic pathways on the early Earth5,6. Due to the discovery of mechanical energy required could come from geological processes ribose and other sugars in meteorites, an extra-terrestrial formose like weathering, erosion and diagenesis. Synthesis in between reaction during aqueous alteration of the parent body and mica sheets induced by their movement due to temperature dif- delivery to the early Earth has also been proposed7. ferences or ocean currents has also been suggested21. Other In solution, the catalytic activity mostly depends on two fac- sources for mechanical energy include tectonics, which might tors: the basicity and the metal ion which can coordinate to the have even been present on the Earth as early as about 4 Ga ago22 oxygen atoms of the sugar compounds8,9. Formaldehyde 1 reacts and can likewise occur on asteroids23. In addition to possibly in the first step via an umpolung step to form glycolaldehyde 2 introducing organic matter, impact events also lead to a (Fig. 1). The mechanism of this dimerisation has not been mechanical energy input and under these conditions the synthesis completely elucidated, yet several possible pathways have been of amino acid derivatives as well as the stability of glycolaldehyde discussed10–12. The dimerisation can be facilitated either photo- have been shown24,25. For laboratory purposes ball milling is the chemically via radical reactions13 or by the use of umpolung standard procedure for performing mechanochemical reactions26, catalysts such as thiazolium salts similar to vitamin B1, which is which have been applied to mineral catalysis and even gaseous involved in the modern metabolism of sugar derivatives14.In reactants27–29. Here we describe the broad applicability for the the competing Cannizzaro reaction, formaldehyde is converted to mechanochemical sugar synthesis and assess the prebiotic viabi- formic acid 7 and methanol 8. As soon as 2 is formed, enolisation lity of the reaction under diverse mineral and atmospheric con- is possible and aldol as well as retro-aldol reactions build up ditions. A range of minerals is shown to catalyse the longer-chain monosaccharides 3–6. Therefore, the circumvention monosaccharide formation from glycolaldehyde 2 and selectively of the umpolung step by the addition of enolisable catalysts or 2 influence the product distribution. Formaldehyde 1 is adsorbed and other sugar products provides an additional approach to on minerals which catalyse its reaction with 2 building trioses to increase reactivity15. Other side reactions are known to occur like heptoses while only marginally producing side products. An 7 8 1 O OH +1 O Umpolung + H H H H H Cannizzaro Reaction HO H formic acid methanol formaldehyde Aldol Reaction Isomerisation +1 ß-Elimination 12 11 OH O 2 910 1,2-Rearrangement O O O O +2 + OH OH OH HO OH dicarbonyl H HO lactic acid compounds glycolaldehyde glycolic acid ethylene glycol +1 +2 3b 3a 4a 4b 16 OH 3c OH OH OH OH O OH O OH OH OH +2 +1 OH OH OH HO H H OH O O OH OH OH O dihydroxyacetone glyceraldehyde aldotetroses erythrulose other branched +3a sugars & +2 +2 +1 +3 side products 17 OH 14 15 5b 5a 6a 6b O OH OH OH OH OH OH O OH OH O OH OH OH OH OH +1 OH OH OH O HO + H H OH OH OH OH O OH OH OH OH OH O OH apiose glycerinic acid glycerol ketopentoses aldopentoses aldohexoses ketohexoses longer-chain monosaccharides Fig. 1 Excerpt of the formose reaction network. Overview of reaction pathways and competing reactions generating monosaccharides and related side products from formaldehyde and a basic catalyst. 2 COMMUNICATIONS CHEMISTRY | (2020) 3:140 | https://doi.org/10.1038/s42004-020-00387-w | www.nature.com/commschem COMMUNICATIONS CHEMISTRY | https://doi.org/10.1038/s42004-020-00387-w ARTICLE umpolung of 1 is achieved with thiazolium salts. Finally, the both micas, but the chromium-rich fuchsite showed nearly double tolerance of the reaction towards gas phases and low tempera- the conversion. For the two montmorillonite clays, that were tures is demonstrated. obtained from different sources and vary in the calcium, magnesium and sodium content, also a significant divergence in conversion was observed. In general, more tetroses than hexoses Results were formed and more aldoses than ketoses, but the ratios are Mineral catalysis. Starting from the classical formose catalyst tremendously influenced by the catalyst. The aldotetroses/ calcium hydroxide and its corresponding mineral portlandite, we erythrulose ratio varied from a value of 5 for basalt to 53 for wanted to explore the catalytic activity of different mineral clas- chabazite. However, not only the equilibrium between aldoses ses. It is not completely certain which minerals are of significance and ketoses can be influenced by the catalyst, but also the in this context, but a summary of possible Hadean minerals has prevalent diastereomer can be chosen. The erythrose/threose ratio been given by Hazen30, which was used as a guideline in the ranged from 0.71 for brucite to 1.23 for montmorillonite 1, selection of minerals. Extending the range of the previously changing the observed main product within the aldotetroses. reported three minerals (portlandite, brucite and sodium mont- Even though the majority of the milling experiments was morillonite clay)20, 18 additional minerals were used. performed at room temperature, sugar formation still occurred, The minerals were tested with 2 as starting material in an albeit to a lesser degree, when performing the reaction under oscillatory ball mill at 30 Hz for 90 min. Representatives of cooling with liquid nitrogen. Hence, the mechanochemical hydroxides, carbonates, sulphates, silicates, micas, zeolites, clays, reaction even tolerates harsher environments and a range of olivines, phosphates, phosphides and borates were used as thermal conditions as well. catalysts. Apart from anhydrite (sulphate mineral) and colema- nite (borate mineral) all minerals showed catalytic activity yielding the aldol products of 2 with even-numbered carbon Formaldehyde incorporation and dimerisation. In the next step, chain length, tetroses 4 and hexoses 6 (Fig. 2). Even the meteoritic 1 was adsorbed on catalytically active minerals, that are also sui- material schreibersite did catalyse the reaction. Previously, it was table as a support. Mineral adsorption of atmospheric form-alde- shown that corroded schreibersite produced an alkaline medium hyde could have played a significant role on the early Earth34. in water and could therefore catalyse this reaction31. In the From the available minerals, zeolites and sheet silicates were mechanochemical setting, the reaction took place even without selected. All showed adsorption capacity and the incorporation of the addition of water. Meteorites can in fact also have an adsorbed 1 when reacting it with 2 in a planetary ball mill for 90 extensive variety of mineral species including quartz, talc, min at 400 rpm.