Isomerism is a fundamental chemical concept, reflecting the fact that the arrangement of atoms in a molecular entity has a profound influence on its chemical and physical properties. Here we describe a previously unclassified fundamental form of conformational isomerism through four resolved stereoisomers of a transoid (BF)O(BF)-quinoxalinoporphyrin. These comprise two pairs of enantiomers that manifest structural relationships not describable within existing IUPAC nomenclature and terminology. They undergo thermal diastereomeric interconversion over a barrier of 104 ± 2 kJ mol−1, which we term ‘akamptisomerization’. Feasible interconversion processes between conceivable synthesis products and reaction intermediates were mapped out by density functional theory calculations, identifying bond-angle inversion (BAI) at a singly bonded atom as the reaction mechanism. We also introduce the necessary BAI stereodescriptors parvo and amplo. Based on an extended polytope formalism of molecular structure and stereoisomerization, BAI-driven akamptisomerization is shown to be the final fundamental type of conformational isomerization.

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  • 27 July 2018

    In the version of this Article originally published, the word ‘stereoisomerism’ was erroneously included in the label of the upper-right box of Fig. 1. The label within the box has been corrected and it now reads: “Constitutional isomerism (same formula, different connectivity)”. This has been corrected in the online version of the Article.


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The authors thank the University of Sydney for a Gritton Scholarship, the Australian Research Council (grants DP0666378, DP0773847 and DP150103137), the National Natural Science Foundation of China (NSFC; grant no. 11674212) and the Shanghai High-End Foreign Experts Grant for funding this research, as well as National Computational Infrastructure (NCI, d63) and INTERSECT (r88) for the provision of computing resources. The authors also give special thanks to G. Price for his help with the Latin terms. This work is dedicated to the stereochemistry pioneers James Kenner FRS 1885-1974 and Kurt Mislow 1923–2017.

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  1. International Centre for Quantum and Molecular Structures and School of Physics, Shanghai University, Shanghai, China

    • Peter J. Canfield
    • , Rika Kobayashi
    •  & Jeffrey R. Reimers
  2. School of Chemistry, The University of Sydney, Sydney, New South Wales, Australia

    • Peter J. Canfield
    • , Iain M. Blake
    • , Zheng-Li Cai
    • , Ian J. Luck
    •  & Maxwell J. Crossley
  3. OraInnova, Darlinghurst, New South Wales, Australia

    • Peter J. Canfield
  4. Research School of Chemistry, Australian National University, Canberra, Australian Capital Territory, Australia

    • Elmars Krausz
  5. National Computational Infrastructure, Australian National University, Canberra, Australian Capital Territory, Australia

    • Rika Kobayashi
  6. School of Mathematical and Physical Sciences, University of Technology Sydney, Sydney, New South Wales, Australia

    • Jeffrey R. Reimers


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P.J.C., J.R.R. and M.J.C. conceived and designed the overall project and wrote the manuscript. I.M.B. was primarily responsible for synthesis (with help from P.J.C. and M.J.C). I.J.L. designed and performed the NMR studies. P.J.C. performed the chiral resolutions, UV–vis, CD and MCD spectroscopies, along with E.K. (who also designed this). P.J.C performed all structural optimizations and NMR calculations, and Z.-L.C. and R.K. designed and performed the UV–vis spectral simulations with R.K. in particular focusing on the difficult question of accurate predictions of chirality. P.J.C. developed the application of the polytope formalism and the nomenclature study. The videos were prepared by P.J.C.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Jeffrey R. Reimers or Maxwell J. Crossley.

Supplementary information

  1. Supplementary Information

    Definitions of isomerization and polytope formalism; Synthesis and characterization; DFT calculations; Nomenclature considerations

  2. Supplementary Video 1

    Compounds 2a, 2b, 3a, 3b

  3. Supplementary Video 2

    Compounds 4a, 4b, 5a and 5b

  4. Supplementary Video 3

    BAI associated vibrational mode

  5. Supplementary Video 4

    BAI reaction coordinate

  6. Supplementary Information

    Cartesian coordinates of all optimized molecular structures

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