Sugars in Space: a Quantum Chemical Study on the Barrierless Formation of Dihydroxyacetone in the Interstellar Medium

Canadian Journal of Chemistry

Sugars in Space: A Quantum Chemical Study on the Barrierless Formation of Dihydroxyacetone in the Interstellar Medium

Journal: Canadian Journal of Chemistry

Manuscript ID cjc-2020-0319.R1

Manuscript Type: Article

Date Submitted by the 14-Oct-2020 Author:

Complete List of Authors: Kong, Aristo ; University of Toronto, Department of Chemistry Guljas, Andrea; University of Toronto, Department of Biochemistry Csizmadia, Imre; University of Toronto, Department of Chemistry; Fournier, Rene;Draft York University, Fiser, Bela; Miskolci Egyetem, Rágyanszki, Anita; York University, Department of Chemistry; University of Toronto

Is the invited manuscript for consideration in a Special Not applicable (regular submission) Issue? :

Astrochemistry, Computational Chemistry, Formose Reaction, Interstellar Keyword: medium

Sugars in Space: A Quantum Chemical Study on the Barrierless Formation of

Dihydroxyacetone in the Interstellar Medium

Aristo Konga, Andrea Guljasb,c, Imre G. Csizmadiaa,d, René Fournierc, Béla Fisere,

and Anita Rágyanszkie*

aDepartment of Chemistry, University of Toronto, 80 St George St, Toronto, ON, Canada M5S 3H6

bDepartment of Biochemistry, University of Toronto, 1 King's College Cir, Toronto, ON, Canada

M5S 1A8

cMolecular Medicine Department, Hospital for Sick Children, 686 Bay St, Toronto, ON, Canada M5G

0A4

dInstitute of Chemistry, University of Miskolc, Miskolc, 3515 Hungary eDepartment of Chemistry, York University,Draft 4700 Keele Street, Toronto, ON, Canada M3J 1P3

*Corresponding author email: [email protected]

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Sugars in Space: A Quantum Chemical Study on the Barrierless Formation of

Dihydroxyacetone in the Interstellar Medium

Aristo Konga, Andrea Guljasa, Imre G. Csizmadiaa,b, René Fournierc, Béla Fiserb,

and Anita Rágyanszkia,c*

Abstract

Among many theories on the life’s origins, regions between star systems in a galaxy is hypothesized to provide prebiotic material on Earth. Simple sugars, including glycolaldehyde, are confirmed to exist in interstellar medium (ISM) and can be intermediates in the formose reaction to form dihydroxyacetone or DHA.

In the studied segment of the formose reaction, hydroxy carbene is sequentially added to formaldehyde, forming glycolaldehydeDraft (hydroxyacetaldehyde) after the first addition and glycerone in the second. The proposed theoretical mechanism was validated through quantum chemical calculations. An exothermic and exergonic pathway favourable in ISM conditions was found, giving a possible explanation for glycerone formation.

The products in question participates in biological processes like energy production, the phosphorylated form of glycerone, DHA-P, participates in glycolysis, and energy storage while glycerone is the source of the glycerine backbone in lipids. The studied reaction is a segment of the formose reaction and further polymerization can lead to pentose and hexose, which take part in the formation of RNA and DNA. Hence, this research explores the hypothesis of exogenous production and delivery of prebiotic material to Earth, building up to the conditions allowing the formation of rudimentary lifeforms.

Keywords: Astrochemistry, Hydroxy Carbene, Interstellar medium, Computational

Chemistry, Formose Reaction

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Introduction

From the very first microorganisms that were able to flourish in the harsh environment

of early Earth, to the astounding diversity and complexity of today’s lifeforms, life as we know

it is the result of billions of years of evolution. Yet, determining how the very first living

organisms appeared is complicated since these events left very little evidence behind. What

were the precursors of these organisms? How did the right components come together to form

these beings? How did these components come to exist in an environment that is theorized to

be drastically unfavourable for life? These are all questions that must be asked when we

consider how life on Earth came to be.

One theory that may answer some of these questions is the “RNA World” hypothesis,

which followed the discovery that RNA is able to fulfil the roles of both genetic material and

catalyst1. Stanley Miller drove the initialDraft wave of research into the RNA World theory when

he hypothesized that components of RNA may have come together spontaneously to form the

precursors for the very first lifeforms2 . The Urey-Miller experiment famously illustrated that

given enough energy input into a system, it is possible to form rudimentary prebiotic material

3 from four simple species: H2O, H2, CH4, and NH3 . However, if these theories are correct, it

remains to be understood how these components came to exist.

An explanation for the formation of early life may be that the components of the first

biotic molecules did not form here. Rather, they may have initially formed in the interstellar

medium (ISM) and been transported to Earth4–7. The conditions in the ISM are more promising

than on early Earth for the synthesis of prebiotic materials: the exotic environments of the ISM

allow molecules that would be unstable on Earth to exist8, while their collisions with other

molecules allow for formation of biotic precursors9. Understanding how these molecules

formed in the ISM may help determine how life began.

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Many factors contribute to the likelihood that early biomolecules formed in the ISM rather than prebiotic Earth. First, although the iron catalysed reaction involving glycolaldehyde

(hydroxyacetaldehyde) was conducted in terrestrial conditions, the transitional metal catalysis of reactions could be applicable to reactions in ISM10. In the ISM, matter aggregates on

“silicate/carbonaceous” dust, which range from 0.1-10μm in size and contain heavier elements that could have catalytic properties, such as Fe, Ni, and Zn8. Organic species, which account for 75 percent of material in interstellar space, aggregate on these dust surfaces and form “ice mantles”8,11. Experimental findings suggest that these surfaces may catalyse the formation of prebiotic material with varying complexities, by using elemental and small substrates found in

12 ISM (i.e. N2, CO, H2) to form simple sugars and organic acids . Moreover, the hypothesis that prebiotic material could be formed in the above manner is supported by studies comparing mass spectroscopic data on interstellarDraft dust and computer simulations of the Urey-Miller experiment13. Another favourable factor could be the hydrogen bonding between the polyols involved in the reaction and surrounding polar species present in the ISM14. These interactions could cause relevant molecules to aggregate onto the surface of ISM dust grains, leading to a higher localised concentration of reactants. In addition, hydrogen bonding between the product and surrounding polar species could thermodynamically stabilize the more substituted polyols or even the transition states14. A final contributor to the plausibility of sugar synthesis in ISM would be the photocatalysis of reactions shown to be possible in terrestrial conditions in situ15.

In this study, we investigate the formation mechanism of glycerone (DHA, dihydroxyacetone) and the possibility of producing more complex sugars in ISM. The formose reaction mechanism, a theory developed in the 1850s and predating the Urey-Miller experiment, describes a mechanism through which formaldehyde polymerises onto itself to from increasingly complex sugars, such as triose, tetrose, pentose, and hexose sugars16,17. The formose reaction has been determined experimentally under basic terrestrial conditions 17. In

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theoretical studies, this reaction is favourable under terrestrial conditions when catalyzed by

water18. Many components of the formose reaction present in the ISM are biologically

significant. Glycolaldehyde, which has been detected in space19, and the larger sugar,

glycerone, are both involved in metabolic functions in biological systems. The phosphorylated

form of glycerone (DHA-P) participates in the production of ATP through glycolysis and thus

is an integral part of metabolic pathways20. DHA-P can also be used as a source of the glycerol

backbone which is essential for fatty acids storage. Furthermore, in the ISM, products of the

formose reaction can react further with formaldehyde and other similar species to polymerize

into more complex molecules, such as sugars and amino acids21. With further polymerization,

pentose monosaccharides such as ribose are formed, which could combine with phosphate

groups to form DNA and RNA22.

The reaction is initiated by transDraft-hydroxycarbene, an isomer of formaldehyde, which

undergoes an isomerization reaction (Figure 1).

H O H O O C H O C H O HO HO OH H H H

Figure 1. The proposed reaction pathway of the formose reaction

Unlike the original formose reaction, hydroxy carbene, an activated form of

formaldehyde, initiates since the original theory’s stepwise reactions between non-activated

formaldehyde molecules would not be feasible in the ISM33. It is more suitable to use the

excited formaldehyde isomer, the trans-hydroxycarbene, as astrochemical reactions require

highly reactive species in order to occur spontaneously.

Hence, in the studied hypothesized mechanism, hydroxy carbene reacts with

formaldehyde to generate glycolaldehyde, which is then consumed by reacting with a second

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hydroxy carbene and produces glyceraldehyde (Figure 1). Formaldehyde and glycolaldehyde

(Figure 1) are also confirmed to be present in sufficient concentration in ISM 23,24. It was shown

theoretically that the cis and trans isomers could exist at significant concentrations in the

ISM25,26.

There is strong evidence for the existence of the excited formaldehyde isomer, trans- hydroxycarbene, in ISM. The mechanism for its formation in terrestrial18,27 and extra- terrestrial28 conditions is supported by theoretical studies. These studies support the hypothesis that materials of biological significance could emerge from the formose reaction in the ISM.

In the present work, a computational chemistry study of the first two steps of the formose reaction, leading up to the formation of glycerone (Figure 1) will be introduced. The formose reaction is selected due to its plausibility in ISM as outlined in one related study on sugar synthesis11 in the ISM on sugarsDraft without a carbonyl group.

Computational Methods

Quantum chemical methods were used to describe the formation mechanism of the glycerone using formose reaction. Quantum chemical calculations for the hypothesized reactions were performed using Gaussian 16 software package29. The molecules were calculated using APFD30 with 6-311G(d) basis set 31,32 to obtain optimized structures, energies, zero-point energies and vibrational frequencies. Vibrational frequencies were all positive, all the structures were minima of the potential energy surface. The pressure and temperature were set according to the conditions in ISM, at 0 atm and 15 K, respectively. The total energy (ΔE0),

Gibbs free energy (ΔG), and enthalpy (ΔH) of each step in the reaction were computed.

Simultaneously, possible structures for transition states and intermediate structures were suggested and computed, optimizing for valid transition states. Once a valid reaction pathway was found, an intrinsic reaction coordinate (IRC) scan was conducted to validate it.

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Thermodynamic properties of each of the studied stages of the reaction were calculated relative

to the reactants (the formaldehyde and trans-hydroxycarbene mixture). Understanding the

quantified thermodynamic properties of the reaction is essential to examine the viability of the

reaction in question.

Draft

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Results and Discussion

We determined the favoured mechanism based on the theory of the polymerization reaction of formaldehyde. However, the original theory involves stepwise reactions between formaldehyde molecules, which is not feasible in the ISM33. It is more suitable to use the excited formaldehyde isomer, the trans-hydroxycarbene, as it is known that astrochemical reactions require highly reactive species in order to occur spontaneously. Using APFD/6-

311G(d) level of theory our calculations suggest that in the given reaction, the energy barriers are small enough that they are not detectable, which is characteristic of some radical reactions.

We thus stipulate that there is no transition state in any steps of the formation of glycerone, making this a barrierless reaction. In the first step, the reaction between formaldehyde and trans-hydroxycarbene, a simple rearrangement reaction, a hydrogen shift, was observed. Draft

Figure 2. The calculated reaction pathway of the formose reaction

Another hydrogen shift was observed in the subsequent reaction between trans- hydroxycarbene and glycolaldehyde (Figure 2). The proposed mechanism contains two

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intermediate structures, both of which involve a hydrogen shift and the formation of a carbon-

carbon bond. (Figure 3). The free energies associated with forming the two intermediate

structures from its previous step were -155.3 kJ/mol and -156.3 kJ/mol, for the first and second

intermediate, respectively (Figure 2). The slight energy difference could be due to the

stabilising effects from the neighbouring hydroxy group of the second hydroxycarbene that is

added in the final step, giving rise to the 1.0 kJ/mol difference.

Draft

Figure 3. The formation mechanism of the glycolaldehyde. The hydrogen shifts from the

first oxygen to the second, while the carbon-carbon bond forms simultaneously

Considering the similarity between the reaction sites of the two intermediate structures,

further reactions resulting in longer carbon chains are plausible given that the ketone

tautomerizes to an aldehyde, producing a terminal carbonyl (Figure 3).

Each step of the formose reaction is exergonic, yielding a ΔG of -313.6 kJ/mol for the

first step and -288.8 kJ/mol for the second step. Based on these theoretical findings, the process

is thermodynamically favourable and spontaneous in the Interstellar medium. This study

reveals a plausible mechanism along the formose reaction that produces three membered

sugars.

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O O H HO OH H C Detected in ISM

H O H O OH O O C H O C H O RNA or HO HO H H H H HO H DNA OH OH OH Detected in ISM Detected in ISM

Figure 4. Formose reaction towards higher-order sugar

The exergonic nature of the reaction and the absence of activation energy in one of two mechanisms shows that the association reaction of formaldehyde and trans-hydroxycarbene is feasible in the ISM. Our results also provide a possible chemical explanation for the presence of glycerone in space. If the remainder of formose reaction proceeds through a similar mechanism, pentoses and hexoses vitalDraft to life could be synthesized in ISM (Figure 4).

Finally, if experimentally confirmed, the exogenous production and delivery of simple sugars to Earth could shed light on the origins of life and the necessary conditions. Specifically, it would provide one explanation to the origins of prebiotic material, in particular those that can only be produced in a reducing environment which is not found in early Earth8; these findings are especially significant in combination with studies on the implausibility of synthesizing prebiotic species in primordial Earth and the delivery of exogenous material on

Earth34. Moreover, through the synthesis of ribose, the findings of this paper could potentially contribute to the RNA world theory, explaining the origins of sugars which constitutes part of the RNA strand.

Two isomers arise in the second step of the reaction, and their outcome likely affects the composition of the projects of this reaction. These studies would further strengthen both our results and the hypothesis that the material necessary for the origins of life on Earth originated extra-terrestrially.

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Conclusion

Through in silico methods, a barrierless mechanisms along the formose reaction is

found. The mechanisms proposed, if confirmed to take place in the ISM, would explain the

origins of glycerone. Moreover, if the mechanism proceeds along the pathways found in this

paper and eventually synthesizing pentoses and hexoses, the findings of this paper could shed

light on how biologically significant sugars could be synthesized in space. In combination with

studies on the implausibility of synthesizing prebiotic species in primordial Earth and the

delivery of exogenous material on Earth34, these findings could contribute to explaining the

formation of life supporting conditions.

Acknowledgements Draft

This research was enabled in part by support provided by SHARCNET

(www.sharcnet.ca/) and Compute Canada (www.computecanada.ca). AR and AG

acknowledge the National Talent Programme, Hungary for the financial support.

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