# Origin of homochirality: The formation and stability of homochiral peptides
in aqueous prebiological environment in the Earth’s crust

Søren Toxvaerd  Department of Science and Environment, Roskilde University,
Postbox 260, DK-4000 Roskilde, Denmark<EMAIL_ADDRESS>
###### Abstract

The oldest forms of living organisms on Earth are about 3,5 billion years old,
and they are found in hydrothermal deposits, and it is often hypothesized that
life originated there. But the hydrothermal systems with a fairly strong flow
of chemical components are not the optimal place for the prebiological self-
assembly of biomolecules and for the emergence of homochirality. This article
examines the possibility for that the self-assembly of homochiral molecules
took place in an aqueous environment in the Earth’s crust. Based on the latest
literature regarding the conditions in the lithosphere there are several
factors that point to that the crust could be the location for the
prebiological self-assembly of biomolecules, and there is nothing against it.
The crust and the mantle contain a substantial amount of water, and at the
time prior to the emergence of life the crust contained most likely the
necessary chemical substances for the synthesis of the biomolecules and an
aqueous environments where the homochirality could be established.

##  I Introduction

Theories about the origin of life often deal with the emergence of homochiral
peptides of L-amino acids and homochiral oligomers of D-carbohydrates. But not
only are the chiral amino acids unstable and with a tendency to racemize Bada
(1972), it is the peptides too Aki (2013); Fujii (2018). The homochirality in
the proteins is vital for the survival of an organism, and the racemization of
Aspartic acid in endospores Liang (2019) and hyperthermophiles Onstott (2014);
Liang (2021) limits the long-time survivability of microorganisms. So the
fundamental question is not only how to get the homochiral peptides, but also
how to maintain the homochirality in the peptides over so long a time that a
self-assembly of the complex homochiral molecules in living systems, can take
place, and a living organism can be created.

The racemization of amino acids ranges from a time span of thousand years at
low temperatures to days at 100 ${}^{\circ}C$, and the racemization is
enhanced in acidic as well as basic solutions Bada (1985). Even if there
somewhere was a pool of water with pH $\approx$ 7 of homochiral amino acid, a
simple synthesis of homochiral peptides from an aqueous solution of homochiral
amino acids can only happen, if the synthesis of biomolecules with homochiral
amino acids was completed within a few thousand years in cold water or within
some days in a hot aqueous solution. But since no one can imagine that it took
so short a time to establish the prebiolocical environment with synthesis of
the complex biomolecules, one must search for environments with the right
conditions, where it is possible to obtain homochiral peptides from a racemic
mixture of amino acids and maintain the environment for million of years,
sufficient to ensure the self-assembly of the homochiral building blocks in
the living organisms.

This article focuses on a possibility for such an environment with formation
and stability of homochiral peptides in an aqueous solution. If it is possible
to synthesize homochiral peptides $from$ $a$ $racemic$ $mixture$ $of$ $amino$
$acids$ in an inorganic aqueous solution under the $right$ $conditions$, this
can explain the emergence of homochirality in peptides Toxvaerd (2017).

##  II The right conditions

Most theories about the emergence of homochirality of the peptides take their
starting point from synthesis of peptides from homochiral amino acids. But
this is as mentioned unrealistic, and furthermore it is not necessary. Kinetic
models indicate that one can obtain homochiral peptides from spontaneous
polymerization of racemic mixtures of amino acids Brandenburg et al. (2005);
Ribo2017 ; Blanco (2017); Buhse2022 ; Pineros2022 . The conditions for
obtaining homochiral peptides from racemic compositions can be specified.
There are the $thermodynamic$ $conditions$ Toxvaerd (2009), but there are also
other conditions, e.g. to the chemistry at the Abiogenesis, and to the
location with the right thermodynamic- and chemical environment.

###  II.1 The right location

All living systems consist of cells with an aqueous solution (cytosol) of ions
and suspensions of biomolecules, and this simple fact makes some demands on
the environment and the location where the self-assembly of the biomolecules
appeared Toxvaerd (2019). One demand to the location of the environment is
that it must have been an aqueous environment, and that life must have arose
in water. Today the water on Earth is present in the oceans, in the lakes, and
in many other locations in our biosphere, but the main part of water on Earth
is present in the crust and mantle beneath the continents and the oceans
Ohtani (2021).

Earth’s lithosphere constitutes the hard and rigid outer layer of the Earth
and includes the crust and the uppermost mantle. The crust is the outermost
solid layer of the Earth below the oceans and the continents. The estimates of
thickness of the crust vary from $\approx$ 10 km below the oceans to $\approx$
70 km below the continents. The crust is separated from the upper part of the
mantle by the ”Moho discontinuity” by a distinct change of the density. The
temperature in the lithosphere increases with the distances from the Earth’s
surface, and reaches a temperature of more than thousand degree at $\approx$
200 km Jeanloz (1986). The synthesis and the stability of peptides requires,
however, a significant lower temperature Vogt (1996); Shao (2010). The crust,
mantle and the ”Hadean ocean” were presumably formed relative shortly after
the Earth was created $\approx$ 4.56 billion years ago Miyazaki (2022), and
the moon, that was formed shortly after the formation of the Earth, was much
closer than it is today and with very strong tide waves in the Hadean ocean
Barboni2017 ; Thiemens2019 ; Green2017  . (The strong tide waves have
accelerated the Moon out to its present position.) Today the water on Earth is
present in the oceans, in the lakes, and in many other locations in our
biosphere, but the main part of water on Earth is present in the crust and
mantle beneath the continents and the oceans. Part of the water in the crust
and the mantle is bound as crystal water, $\textrm{H}_{2}\textrm{O}(c)$, but
an essential part is present as water $\textrm{H}_{2}\textrm{O}(aq)$. The
evidence for water in the crust and mantle is indirect and based on extensive
seismic velocity measurements, electrical and thermal conductivity
measurements, geodetic data, mineral physics, geochemical data, and modeling
Ohtani (2021); Harrison2020 . But although the indications of water in the
crust and the mantle there is, however, no direct determinations of whether
$\textrm{H}_{2}\textrm{O}(aq)$ appears as capillary or bulk water. The review
Ohtani (2021) gives an estimate of the total amount of water of 2.6-8.3 ocean
masses ( $\textrm{H}_{2}\textrm{O}$(c)+ $\textrm{H}_{2}\textrm{O}$(aq)). The
water in the crust and mantle is released in the hydrothermal vents, and the
right place for prebiological self-assembly of organic molecules could very
well be the $\textrm{H}_{2}\textrm{O}(aq)$ somewhere in the Earth’s crust.

A support for this hypothesis is the fact that the oldest signs of life, which
are at least 3.5 billion years old, appear as fossilized microorganisms
(bacteria) found in hydrothermal vent precipitates Djokic (2017); Schopf
(2018); Cavalazzi (2021); Dodd (2017). There are also direct measurements of a
biosphere in the upper part of the wet crust, which today contains bacterias
Li2020 ; Takamiya (2021). Here we argue for that the the location for
prebiological self-assembly of homochiral peptides is a wet crust in the
Hadean Eon.

A relationship that supports the hypothesis is the chemical composition of the
cytosol. The cytosol contains sodium and potassium ions, and the
concentrations of potassium and sodium in living systems differs significantly
from the corresponding composition in the oceans. The ion content in the
cytosol points to a location in the crust for self-assembly of biomolecules
and not to the Hadean ocean with a composition of salt, which probably have
been similar to the composition in today’s oceans Harrison (2009);
Harrison2020a . The concentration of potassium
$[\textrm{K}_{\textrm{cytosol}}^{+}]\approx$0.10 M, and the ratio between the
concentration of potassium ions and sodium ions
$[\textrm{K}_{\textrm{cytosol}}^{+}]/[\textrm{Na}_{\textrm{cytosol}}^{+}]\approx
10$
in the cytosol in the biocells deviate very much from the corresponding
concentration of potassium $[\textrm{K}_{\textrm{oceans}}^{+}]\approx$0.01022
M and the ratio
$[\textrm{K}_{\textrm{oceans}}^{+}]/[\textrm{Na}_{\textrm{oceans}}^{+}]=0.0102/0.469=0.0217$
in today’s oceans. The ratio
$[\textrm{K}_{\textrm{oceans}}^{+}]/[\textrm{Na}_{\textrm{oceans}}^{+}]$ is
crucial for the membrane potential and the sodium-potassium pump in the cells,
and a high concentration of potassium and the right ratio between sodium and
potassium could be present somewhere in the crust and in mica sheets in the
upper part of the mantle Hansma (2021). Another example in this context is the
appearance of phosphor esters in biological systems, in the membranes, in RNA,
in DNA, in the Glycolysis, and in many other biomolecules. But whereas the
concentration of phosphates in the oceans in general are low Paytan (2007),
phosphates is more common in the crust Walton (2021); Flores (2022).

Capillaries are locations where it, opposed to the oceans is possible to
obtain and maintain a relative high concentration of amino acids. This is an
important condition for the thermodynamics and kinetics at the prebiological
bio-synthesis (see later). Many scientists have suggested that life originated
in the hydrodynamic vents and serpentinites in the oceans Cleaves (2009);
Branscomb (2018) in accordance with earliest sign of life on Earth. The
environment in the hydrothermal vents and serpentinites above the wet crust
and mantle is turbulent and with a rapid exchange of matter Moore (2021). If
the prebiological synthesis of the biomolecules appeared over a long period of
time it seems more likely, that a confined water system in the crust with a
small, but constant input of the chemical reactants in the biosynthesis, and
with a slow synthesis of the biomolecules over a time period of many million
of years, is the right location for prebiological synthesis of the
biomolecules .

This article examines the possibility, that the self-assembly of homochiral
molecules originated in an aqueous environment in the Earth’s crust.

###  II.2 The thermodynamic condition

A suspension of homochiral peptides in an aqueous environment is stable if the
peptides are in structures with minimum free energy. The peptides are polymers
of units of amino acids, combined via amide bonds. The stability of peptides
increases with temperature relative to hydrolysis reactions in aqueous
solutions, and become a facile process in hydrothermal systems deep in
sedimentary basins Shock (1992); Takahagi (2019); Pedreira-Segade (2019). A
homochiral L-peptide in an aqueous ionic suspension is stable if there is a
sufficient ”chiral discrimination”. The chiral discrimination for a homochiral
L-peptide is given by the difference in Gibbs free energies of the peptide and
the peptide with one (or more) D- configuration of its chiral units. This
requirement can be specified:

The increase in reaction enthalpy $\Delta H_{r}(aq)$ by a change of chirality
of one L-configuration to a D-configuration in the homochiral peptide in an
aqueous ionic suspension shall exceed the decrease of reaction energy
$-T\Delta S_{r}(aq)$ by the gain in entropy.

The excess of of reaction enthalpy measured in units of $RT\approx$ 2.5 kJ/mol
must be several units in order to ensure the stability of the homochiral
conformation Toxvaerd (2009). As mentioned especially the Aspartic acid units
in the proteins are unstable and racemizate with consequence for the
survivability of biosystems Liang (2019, 2021).

Figure 1: The secondary $\alpha$-helix structure of a homochiral peptide chain
Pauling (1951). The secondary structure is stabilized by (weak) hydrogen
bonds. Each amide group is hydrogen bounded to the third (or fifth) amide
group beyond it along the helix. The $\alpha$-helix structure to the left of
the figure is found in nature.

The structure of a homochiral peptide is primarily given by its secondary
structure, first determined by Pauling Pauling (1951). Perhaps the figure of
the $\alpha$-helix structure in Pauling et al’s article best illustrates the
condition for thermodynamic stability of a homochiral peptide in an aqueous
suspension. The clockwise (positive) $\alpha$-helix structure (to the left) on
Figure 1 with amide units of L-amino acids was derived from spectroscopic data
for bond lengths and angles at the planar peptide units, and with an
$\it{intramolecular}$ stabilizing hydrogen-bond between a hydrogen atom at the
substituted -N-H and an oxygen atom in a -C=O group in the helix. The helix is
obtained for peptides with homochiral amino acids, by which the overall
orientation changes with a constant angle at each peptide bond. The angle at
the peptide bond is changed if an L configuration is changed to a D
configuration, and the $\alpha$-helix structure is destroyed. This fact is
confirmed by the observation, that a chiral change of an L-structure to a
D-structure in one chiral unit is associated with a loss of the secondary
structure of the peptide and an increased concentration of water molecules in
a peptide Fujii (2010).

The effect of an ionic aqueous solution on the enthalpy of a homochiral
peptide is not known, but one shall a priori expect that the stability of the
$\alpha$-helix structure is stabilized by increasing ionic activity and
thereby decreasing activity of the water molecules (Debye–Hückel theory). The
energy of the -N-H$\cdot\cdot\cdot$O=C- hydrogen bond ($\approx$ 10 kJ/mol) is
only of the order of one half of the energy of a hydrogen bond in pure water
Wendler (2010), and the stabilizing intramolacular hydrogen bond is in
competition with hydrogen bonds to the water molecules in the solvent. The
ions in the cytosol decrease the water activity and thereby the difference in
energies between the intramolecular hydrogen bonds in the peptide and a
hydrogen bond with water molecules in the cytosol. This fact is in agreement
with the simulations of simple chain molecules in a solvent with different
activities Toxvaerd (2017) which show, that a decreasing activity of the
solvent stabilizes the compact conformation of the polymer.

There is another thermodynamic requirement to a prebiological synthesis of
peptides in a wet crust. The synthesis of the biomolecules in the aqueous
environment requires on one hand a certain temperature, and on the other hand
biomolecules are unstable and decompose at high temperatures. Only very little
is, however, known about the temperature in the crust and mantle in the Hadean
Eon Harrison2020a .

The thermodynamics requirement to the right place for maintaining peptides
over long times in homochiral secondary (or higher order) structures is an
aqueous solution with a reduced water activity, given by the concentrations of
the ions in the water. A high electrolyte concentration, higher than in the
cytosol can be present in wet capillaries in the crust.

###  II.3 The conditions to the chemistry at the Abiogenesis

The conditions to the chemistry at the Abiogenesis can be specified: There are
the conditions to the chemical reactions by which the homochiral peptides and
carbohydrates are synthesized from racemic compositions, and there are the
conditions to chemical composition in the crust.

####  II.3.1 The conditions to the chemical reactions: The Frank model

The synthesis of homochiral polymers can be obtained by consecutive reactions,
first described by C. F. Frank Frank (1957). In 1953 he published a
theoretical model for spontaneous asymmetric synthesis, and the emergence of
homochirality at the polymerization of peptides is an example of such a
synthesis. Since then numerous of articles with asymmetrical polymerization
and chiral amplification have been published Brandenburg et al. (2005);
Ribo2017 ; Blanco (2017); Buhse2022 ; Pineros2022 ; Shen (2021). An important
and necessary condition to the network of consecutive reactions is as
mentioned the inclusion of the racemization of the monomers. This is included
in a several of the reaction schemes in the articles Ribo2017 ; Blanco (2017);
Buhse2022 ; Pineros2022 , where the kinetics reactions for racemization of the
chiral monomers are together with autocatalytic polymerization and merging of
polymers, and the reaction equations with homochiral peptides are solved for
various values of reaction constants.

The asymmetric polymerization, obtained by Frank models can lead to homo
chiral peptides, but with equal possibility for a both enantiomers (Pauling’s
polymers in Figure 1 are in fact for secondary structures of peptides with
D-amino acid units Dunitz (2001)). The dominance of the L-conformations of
peptides may be caused by the weak parity violating nuclear forces. This
impact is, however, very small, and the dominance can also be obtained by a
self-reinforcing dominance of homochiral domains. Toxvaerd2000 ; Toxvaerd
(2009).

The necessary chiral discrimination for a symmetry break and homochiral
purification is indirectly given by the ratios of the reaction constants
Toxvaerd2000 . According to the thermodynamic condition in Section 2.2, an
important details in the reaction scheme for the consecutive polymerization
reaction is the chiral discrimination, given by the hydrogen bonds in the
secondary structure of the peptides in an ionic aqueous solution. The impact
of these complicated effects of the conformation of the polymer in the ionic
environment is, however, not included in the Frank models for homochirality
obtained by polymerization, where the chiral discrimination from the reaction
enthalpies is given by the ratios of the reaction constants.

The articles with chiral amplification are for polymerization with uniform
(bulk) concentrations of the species Brandenburg et al. (2005); Ribo2017 ;
Blanco (2017); Buhse2022 ; Pineros2022 ; Shen (2021). An extension to more
realistic reaction-diffusion Turing models with local concentrations
Turing1952  is, however, complicated and moreover the homochiral purification
might have been obtained in capillaries in the crust. A reaction-diffusion
Frank model for the polymerization in a confined geometry is complicated and
difficult to evaluate, but reaction-diffusion models for consecutive reactions
in confined geometry have been developed and evaluated Hunding1990 .

Chemical reactions in fluid phases are rather insensitive with respect to the
pressure changes. The changes of partial Gibbs free energies with respect to a
pressure change are given by the partial volumes of the components in the
solution, and the Gibbs free energy effects by a pressure change are generally
small. The polymerization to homochiral peptides might lead to a slightly
higher density of the suspension, an if so the increased pressure in the crust
will enhance the polymerization rate, but it will not affect the symmetry
break because homochiral suspensions with peptides with pure D- or L-units
have the same density.

In summary: The kinetics with racemization kinetics of the amino acids and
with polymerization to homochiral peptides can be described by a Frank model.
The thermodynamic stability of the homochiral peptides are ensured by intra-
molecular hydrogen bonds in the higher order structures in competition with
hydrogen bonds with the water molecules in the solvent, which destabilize the
secondary structure. It is, however, difficult to take this effect into
account in the kinetic in the Frank models.

####  II.3.2 The chemical composition

The chemical composition of the Earth’s crust and upper part of the mantle
4-4.5 billion years ago is not known, but today the solid mantle consists
mainly of Mg, Si and Fe Anderson (1983); Lyubetskaya (2007) . In determining
the chemical composition of the crust and the mantle one utilizes
cosmochemical data, based on the assumption that the sun, planets and
meteorites all originated from the solar nebular. Chondritic meteorites are
considered the most representative samples of the solid nebular material
Lyubetskaya (2007). Today, the crust may only contains small amount of organic
materials such as amino acids Pisapia (2018) and carbohydrates Sforna (2018),
and 2.7 billion year old rocks contained acetate and formate Lollar (2021).

The most interesting chondrites are the carbonaceous chondrites. Not only do
they contain carbon, but also organic molecules an among these also amino
acids and purine and pyrimidine nucleobases Oba (2022). There exists many
investigations of the chemical composition in the carbonaceous chondrites and
the composition of amino acids Aponte (2020); Glavin (2020). The amino acids
appear with a small excess of L-amino acids, which is to be expected since
strong baryonic forces in the universe favor the L-configurations. However,
these small excesses of chirality are, as mentioned irrelevant for the origin
of homochirality of peptides in aqueous solutions, because the amino acids
racemizate rapidly. But if a part of the crust or the mantle consisted of the
same materials as the carbonaceous chondrites some organic molecules might
have survived the heating of the Earth at its formation, and the carbonaceous
chondrites material might have been a source of amino acids at the
polymerization of peptides in the crust. There are also investigations which
makes it probable, that amides can be directly synthesized at thermodynamic
conditions similar to the conditions in the crust Robinson (2021); Fu (2022);
Yang (2022).

Carbohydrates are found in carbonaceous chondrites Furukawa (2019), but they
can also be synthesized from carbon dioxide and methane, two component which
also were present in the nebular material at the formation of the Earth and
our solar system Guzmań-Marmolejo & Segura (2015). The first step in the
synthesis of the carbohydrates is formaldehyde, CH2O, which is synthesized
from carbon dioxide and methane Schlesinger & Miller (1983), and the the
succeeding spontaneous condensation of formaldehyde is the formose reaction,
which was discovered already in 1861 Butlerow (1861). The formose reaction is
well known and is believed to be the basic synthesis of bio-carbohydrates and
related bio-organic molecules Gabel and Ponnamperuma (1967); Washington
(2000); Kim et al. (2011); Jalbout et al. (2007); Lambert et al. (2010). The
condensation into carbohydrates is catalyzed by not only amino acids Weber
(2001); but also by naturally aluminosilicates occurring in the mantle
Anderson (1983).

In summary: The early lithosphere most likely contained the basic chemical
ingredients, carbon dioxide and methane and ammonia, for synthesis of
carbohydrates and peptides.

##  III Conclusion

The oldest signs of cellular life on Earth are about 3,5 billion years old
Djokic (2017); Cavalazzi (2021), and they are found in a volcanic-hydrothermal
(hot springs, geysers) system and in hydrothermal veins deposits, and it is
often hypothesized that life originated there. But the hydrothemal systems
with a fairly strong flow of chemical components are not the optimal place for
the prebiological self-assembly of biomolecules and for the emergence of
homochirality. This article examines the possibility for that the self-
assembly of homochiral molecules originated in an aqueous environment in the
Earth’s crust.

Based on the latest literature regarding the conditions in the Earth’s crust
and upper part of the mantle there are several factors that point to, that the
crust could be the location for the prebiological self-assembly of
biomolecules, and there is nothing against it. The crust and the upper part of
the mantle contains a substantial amount of water Ohtani (2021), and a
substantial biomass and biodiversity Takamiya (2021), with an estimated number
of (Prokaryotic) cells of the order 2 to 6$\times 10^{29}$ Magnabosco (2018).
The crust and upper part of the mantle at the time prior to the emergence of
life contained the necessary chemical substances for the synthesis of the
biomolecules, and an aqueous environment in the crust beneath hydrothermal
locations is a more likely place for the prebiological synthesis of peptides
and carbohydrates and for the establishment of homochirality.

A wet crust can generally be a suitable place for the biochemical evolution
primordial stages. Here we have advocated for the Earth’s crust in the Hadean
Eon as the most likely place, but it might as well have been on Mars. The
requirement to a moderate temperature for synthesis of stable biomolecules
sets a limit to how soon after the emergence of the solar system such a
biosynthesis could take place, and this fact is in favour of Mars, which is a
terrestrial planet similar to Earth. It was created at the same time as the
Earth, but cooled down before the Earth Plesa2018 .

Acknowledgment

The anonymous, but constructive referee reports are gratefully acknowledged.
This work was supported by the VILLUM Foundation’s Matter project, grant No.
16515.

References

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