# Origin of Single-Molecule Reaction Chirality

**Authors:** Chen Yang, Shuyao Zhou, Yilin Guo, Xinmiao Xie, Ju Wang, Yanwei Li, Jingyuan Hu, Linghai Xie, Zhirong Liu, Guangwu Li, Xuefeng Guo

PMC · DOI: 10.34133/research.1150 · Research · 2026-02-24

## TL;DR

This paper explores how single-molecule reactions can spontaneously break mirror symmetry, offering insights into the origin of molecular chirality and implications for chiral synthesis.

## Contribution

A new method for real-time monitoring of single-molecule chirality evolution with single-event resolution is introduced.

## Key findings

- Spontaneous mirror symmetry breaking was directly observed in a single-molecule Diels–Alder reaction system.
- An external electric field enabled universal asymmetric synthesis without a catalyst.
- Symmetry breaking depends on the number of molecules and coupling with the external environment.

## Abstract

The origin of molecular chirality remains an enigma in chemistry, particularly regarding how single-molecule events overcome intrinsic stochasticity to establish population-level chirality. Here, we present a viable strategy for real-time, from-the-beginning single-molecule trajectory monitoring of asymmetric evolution from a single initial molecule with single-event resolution, allowing direct observation of spontaneous mirror symmetry breaking in a single-molecule Diels–Alder reaction system. We monitor the asymmetric evolution in real time using the chirality-induced spin selectivity effect. This approach enables the capture of initial symmetry breaking at the single-molecule level and the identification of the excess-compensation mechanism. In addition, the introduction of an external electric field to the symmetry-breaking species enables universal asymmetric synthesis without the need for a catalyst. The increase in the number of molecules leads to symmetry breaking, which is also contingent on the coupling with the external environment. This work deepens our understanding of the molecular principles underlying the origin of life and has many implications for precise chiral synthesis and drug design.

## Full-text entities

- **Chemicals:** Trifluoroacetic acid (MESH:D014269), acetone (MESH:D000096), Cr (MESH:D002857), l-amino acids (MESH:D000596), SiO2 (MESH:D012822), pyridine (MESH:C023666), graphene (MESH:D006108), 9-phenyl-9-fluorenol (-), silicon (MESH:D012825), Al (MESH:D000535), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (MESH:C000613388), S (MESH:D013455), halogen (MESH:D006219), ester (MESH:D004952), FeCl3 (MESH:C024555), fluorene (MESH:C041509), C (MESH:D002244), Ni (MESH:D009532), carboxylic acid (MESH:D002264), N2 (MESH:D009584), oxygen (MESH:D010100), acrylate (MESH:C036658), Au (MESH:D006046), acetic acid (MESH:D019342), isoprene (MESH:C005059), copper (MESH:D003300), GMG (MESH:C118417), Al2O3 (MESH:D000537), benzene (MESH:D001554), water (MESH:D014867), PMMA (MESH:D019904)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12929813/full.md

## References

43 references — full list in the complete paper: https://tomesphere.com/paper/PMC12929813/full.md

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Source: https://tomesphere.com/paper/PMC12929813