The source review (Hein & Blackmond, Acc. Chem. Res. 2012) established, via reciprocal resolution experiments, that a small enantiomeric excess (ee) in either the amino-acid pool or the sugar pool can enantioenrich the other, and posed the resulting 'chicken or egg' question: which class of molecules was enantioenriched first on the early Earth, and what geochemically plausible process generated and sustained the initial bias? A decade of follow-up work has strengthened the reciprocity (sugars drive amino-acid enantioenrichment and vice versa), and has produced candidate bias-generation mechanisms (spin-selective crystallization on magnetic minerals, heterochiral ligation, autocatalytic feedback networks) plus a proposed network-scale scenario, but reviews through 2025 still describe the origin of the initial chiral bias and the which-first question as unresolved. The problem asks for a geochemically plausible account of the initial bias — or a demonstration that internal symmetry breaking makes an external initial bias unnecessary — together with a discriminated answer to whether amino acids, sugars, or neither pool was enantioenriched first.

Background

Life's building blocks are homochiral: proteins are built almost exclusively from L-amino acids while nucleic acids contain only D-sugars. The two mirror-image forms of a chiral molecule (enantiomers) are produced in equal amounts by ordinary abiotic synthesis, so the prebiotic world is presumed to have been racemic (equal D and L). The imbalance is quantified as the enantiomeric excess, ee=∣D−L∣/(D+L)×100%\mathrm{ee} = |D - L|/(D + L) \times 100\%. Explaining how a racemic prebiotic world produced single-handed biomolecules is a central unresolved problem of origins-of-life chemistry.

Frank-type autocatalysis (autocatalytic production of each enantiomer that catalyzes its own formation, combined with mutual inhibition) can amplify a tiny imbalance in theory, and one laboratory reaction — an autocatalytic organozinc addition — realizes amplifying asymmetric autocatalysis, but it has no prebiotic relevance (as summarized in Blackmond's 2019 review and Higgs & Blackmond 2025). Candidate external sources of a small initial ee include circularly polarized light (starlight whose electric field rotates in one sense, which photolyzes one enantiomer marginally faster than the other), parity violation (the minuscule energy difference between enantiomers predicted by the weak nuclear force), and meteoritic delivery: carbonaceous meteorites show L-excesses in some amino acids — the nonproteinogenic isovaline shows variable excesses, and some protein amino acids reach roughly 60% ee in rare cases (Elsila et al. 2016). The missing step has been connecting any such initial bias to prebiotic reaction chemistry.

Hein & Blackmond (2012) reviewed the coupling of chiral amplification to prebiotic synthesis in the context of RNA-world chemistry (the hypothesis that RNA-like molecules preceded DNA and proteins). In the prebiotic nucleotide synthesis developed by Sutherland and coworkers, racemic glyceraldehyde (a three-carbon sugar) and 2-amino-oxazole form RNA-precursor molecules; the amino acid proline mediates a kinetic resolution (preferential consumption of one enantiomer of a racemate, enriching the remainder) of glyceraldehyde, amplifying a small sugar ee; conversely, chiral sugars mediate enantioselective Strecker-type synthesis (formation of aminonitriles, amino-acid precursors, from aldehyde, ammonia, and cyanide) and hydrolytic kinetic resolution of aminonitriles. Since either pool can seed the other, the review posed an explicit 'chicken or egg' scenario and asked which pool came first and where the initial imbalance came from.

More recent work has demonstrated candidate mechanisms that could generate a bias without any pre-existing ee: spin-selective crystallization of a racemic RNA precursor on the magnetic mineral magnetite, driven by the chiral-induced spin selectivity effect (chiral crystals transmit one electron-spin orientation preferentially, so a magnetized surface selects which hand crystallizes), and autocatalytic feedback networks that break symmetry stochastically from a racemic start. None of these has yet been established as the actual early-Earth account.

Problem Statement

Given the experimentally demonstrated reciprocal resolution between the prebiotic amino-acid and sugar pools — a small enantiomeric excess in either pool can, through the proline–glyceraldehyde–2-amino-oxazole and sugar-mediated Strecker/hydrolytic-resolution chemistries, enantioenrich the other — determine the origin of the initial chiral bias underlying terrestrial homochirality. Specifically: (i) identify the geochemically plausible process that generated and sustained the first non-racemic enantiomeric excess (nonzero ee) in prebiotic amino acids or in prebiotic sugars from a presumably racemic prebiotic world under early-Earth conditions — or establish that stochastic symmetry breaking within an autocatalytic prebiotic network rendered any external initial bias unnecessary; and (ii) on that basis, discriminate which pool — amino acids, sugars, or neither — was enantioenriched first on the early Earth. Here 'geochemically plausible' means an account consistent with known early-Earth conditions and supported by the cited experimental or theoretical work, not one that requires a new laboratory demonstration under simulated early-Earth conditions; and the option 'neither' in (ii) asserts that no ordering existed in which one of the two pools was enantioenriched before the other (the branch of (i) in which internal symmetry breaking makes an external initial bias unnecessary), not that some third molecular class was necessarily enantioenriched first.

References

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