A 2017 thermodynamic and molecular-dynamics study by S. Toxvaerd proposed that homochirality can be established and maintained at low water activity inside the hydrophobic cores of sufficiently long peptides, and suggested that concentrated aqueous solutions of amino acids and carbohydrates, possibly at elevated ionic strength, could undergo spontaneous chiral purification in the presence of such peptides. The proposal left its central prediction experimentally untested: the paper explicitly called for experiments on such concentrated aqueous solutions to reveal whether spontaneous chiral purification and the maintenance of homochirality are possible in the presence of peptides with hydrophobic cores. The source also cited known cross-chiral discrimination between different amino acids and between amino acids and carbohydrates as something that 'can explain' the overall dominance of D-carbohydrates and L-amino acids, without working out a mechanism, and its prediction rests on coarse-grained simulations.

Background

Life on Earth is homochiral: proteins are polymers of L-amino acids and carbohydrates and nucleic-acid sugars are of D-configuration, whereas ordinary chemical synthesis and most extraterrestrial organic matter are racemic (equal mixtures of both mirror-image forms). Homochirality is also not permanently stable: L-amino-acid residues in peptides slowly racemize (convert to the D form) in aqueous biological environments, a process implicated in peptide aging and in the accumulation of D-aspartic acid in aged tissues. 'Water activity' denotes the effective availability of water as a solvent in a mixture; it decreases when solutes are concentrated, and intracellular water is close in activity to bulk water. 'Chiral discrimination' is the phenomenon that a chiral molecule packs or interacts differently with a copy of itself than with its mirror image; if the enthalpy gain of homochiral pairing exceeds the entropy cost of demixing, about RTln⁡2≈2RT\ln 2 \approx 2 kJ/mol at room temperature, a racemic fluid can phase-separate into homochiral domains. Such spontaneous mirror-symmetry breaking has been observed experimentally in isotropic liquids (Dressel et al., Nature Chemistry 2014). Toxvaerd (2017) combined a thermodynamic analysis with extensive coarse-grained molecular dynamics simulations of model peptides built from 'united-atom' Lennard-Jones particles — simplified interaction sites that each stand for a whole chemical group rather than individual atoms — in which chiral discrimination was imposed by letting like enantiomer pairs attract over a longer range than unlike pairs, and racemization was modeled by an explicit bimolecular isomerization kinetics D+D⇌D+L⇌L+LD+D \rightleftharpoons D+L \rightleftharpoons L+L with a lower activation energy for unlike pairs. The simulations showed that peptides with roughly a thousand or more chiral units and sufficiently strong discrimination spontaneously break mirror symmetry and maintain homochirality when the water mole fraction is below about 0.20, while shorter chains remain racemic and compact homochiral peptides racemize again at higher water activity. On this basis the paper proposed that the peptides in primordial enzymes acted as stereospecific backbones that purified amino acids and carbohydrates of one chirality, and that homochirality must have been established at a water activity lower than that of the modern cytosol. Independently, mass-spectrometry cluster studies had shown strong chiral recognition between amino acids and simple carbohydrates — notably between D-glyceraldehyde and L-serine — and Breslow and Cheng (2010) demonstrated that L-amino acids catalyze a small excess of D-glyceraldehyde, so a cooperative link between amino-acid and carbohydrate chirality is chemically plausible but was not worked out into a mechanism. To date, no experimental test of this prediction has been reported, and the mechanism has been studied only through coarse-grained simulations.

Problem Statement

The problem arising from Toxvaerd (2017) is the experimental test the source paper explicitly calls for: determine whether spontaneous chiral purification and the maintenance of homochirality occur in concentrated aqueous solutions of amino acids and carbohydrates, at reduced water activity (either through elevated solute concentration or through elevated ionic concentration), in the presence of peptides with hydrophobic cores — that is, resolve whether homochirality can in fact be established and maintained at low water activity through the hydrophobic cores of sufficiently long peptides, the question being about the general class of such solutions rather than a single chosen instance.

References

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  2. Christian Dressel, Tino Reppe, Marko Prehm, Marcel Brautzsch, Carsten Tschierske, 'Chiral self-sorting and amplification in isotropic liquids of achiral molecules', Nature Chemistry 6 (2014), DOI:10.1038/nchem.2039, https://doi.org/10.1038/nchem.2039
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