Abstract

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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References

  1. 1.

    McNaught, A. D. & Wilkinson, A. IUPAC Compendium of Chemical Terminology — The Gold Book 2nd edn (Blackwell, Oxford, 1997).

  2. 2.

    Testa, B., Caldwell, J. & Kisakürek, M. V. Organic stereochemistry: guiding principles and bio-medicinal relevance. A general introduction to the series. Helv. Chim. Acta 96, 1–3 (2013).

  3. 3.

    Testa, B., Vistoli, G. & Pedretti, A. Organic stereochemistry. Part 1. Symmetry elements and operations, classification of stereoisomers. Helv. Chim. Acta 96, 4–30 (2013).

  4. 4.

    Testa, B. Organic stereochemistry. Part 2. Stereoisomerism resulting from one or several stereogenic centers. Helv. Chim. Acta 96, 159–188 (2013).

  5. 5.

    Testa, B. Organic stereochemistry. Part 3. Other stereogenic elements: axes of chirality, planes of chirality, helicity, and (E,Z)-diastereoisomerism. Helv. Chim. Acta 96, 351–374 (2013).

  6. 6.

    Testa, B., Vistoli, G. & Pedretti, A. Organic stereochemistry. Part 4. Isomerisms about single bonds and in cyclic systems. Helv. Chim. Acta 96, 564–623 (2013).

  7. 7.

    Testa, B., Vistoli, G., Pedretti, A. & Caldwell, J. Organic stereochemistry. Part 5. Stereoselectivity in molecular and clinical pharmacology. Helv. Chim. Acta 96, 747–798 (2013).

  8. 8.

    Vistoli, G., Testa, B. & Pedretti, A. Organic stereochemistry. Part 6. The conformation factor in molecular pharmacology. Helv. Chim. Acta 96, 1005–1031 (2013).

  9. 9.

    Testa, B. Organic stereochemistry. Part 7. The concept of substrate stereoselectivity in biochemistry and xenobiotic metabolism. Helv. Chim. Acta 96, 1203–1234 (2013).

  10. 10.

    Testa, B. Organic stereochemistry. Part 8. Prostereoisomerism and the concept of product stereoselectivity in biochemistry and xenobiotic metabolism. Helv. Chim. Acta 96, 1409–1451 (2013).

  11. 11.

    King, H. The possibility of a new instance of optical activity without an asymmetric carbon atom. Proc. Chem. Soc. Lond. 30, 249–251 (1914).

  12. 12.

    Cain, J. C. & Micklethwait, F. M. G. Studies in the diphenyl series. Part VI. The configuration of diphenyl and its derivatives. J. Chem. Soc. Trans. 105, 1437–1441 (1914).

  13. 13.

    Christie, G. H. & Kenner, J. The molecular configurations of polynuclear aromatic compounds. Part I. The resolution of γ-6:6′-dinitro- and 4:6:4′:6′-tetranitro-diphenic acids into optically active components. J. Chem. Soc. Trans. 121, 614–620 (1922).

  14. 14.

    Kuhn, R. In Molekulare Asymmetrie 803–824 (Franz-Deutike, Leipzig, 1933).

  15. 15.

    Horner, L. et al. Phosphororganische verbindungen optisch aktive tertiäre Phosphine aus optisch aktiven quartären Phosphoniumsalzen. Tetrahedron Lett. 2, 161–166 (1961).

  16. 16.

    Brois, S. J. Aziridines. XII. Isolation of a stable nitrogen pyramid. J. Am. Chem. Soc. 90, 508–509 (1968).

  17. 17.

    Muetterties, E. L. Topological representation of stereoisomerism. I. Polytopal rearrangements. J. Am. Chem. Soc. 91, 1636–1643 (1969).

  18. 18.

    Muetterties, E. L. & Storr, A. T. Topological analysis of polytopal rearrangements. Sufficient conditions for closure. J. Am. Chem. Soc. 91, 3098–3099 (1969).

  19. 19.

    Muetterties, E. L. Topological representation of stereoisomerism. II The five-atom family. J. Am. Chem. Soc. 91, 4115–4122 (1969).

  20. 20.

    Meakin, P. et al. Structure and stereochemical nonrigidity of six-coordinate complexes. J. Am. Chem. Soc. 92, 3482–3484 (1970).

  21. 21.

    Muetterties, E. L., Wiersema, R. J. & Hawthorne, M. F. Detection of polytopal isomers in the solution state. I. Eight-atom family. J. Am. Chem. Soc. 95, 7520–7522 (1973).

  22. 22.

    Muetterties, E. L. & Guggenberger, L. J. Idealized polytopal forms. Description of real molecules referenced to idealized polygons or polyhedra in geometric reaction path form. J. Am. Chem. Soc. 96, 1748–1756 (1974).

  23. 23.

    Muetterties, E. L. Polytopal form and isomerism. Tetrahedron 30, 1595–1604 (1974).

  24. 24.

    Guggenberger, L. J. & Muetterties, E. L. Reaction path analysis. 2. The nine-atom family. J. Am. Chem. Soc. 98, 7221–7225 (1976).

  25. 25.

    Hoffmann, R., Beier, B. F., Muetterties, E. L. & Rossi, A. R. Seven-coordination. A molecular orbital exploration of structure, stereochemistry, and reaction dynamics. Inorg. Chem. 16, 511–522 (1977).

  26. 26.

    Debolt, L. C. & Mark, J. E. Effects of bond-angle inversion on the statistical properties of poly(dimethylsiloxane). J. Polym. Sci. B 26, 989–995 (1988).

  27. 27.

    Kalinowski, H.-O. & Kessler, H. in Topics in Stereochemistry Vol. 7 (eds Allinger, N. L. & Eliel, E. l.) 295–384 (Wiley Interscience, New York, 1973).

  28. 28.

    Kessler, H. Thermal isomerization about double bonds. Rotation and inversion. Tetrahedron 30, 1861–1870 (1974).

  29. 29.

    Gozlan, H., Michelot, R., Riche, C. & Rips, R. Amide-oximes: determination des configurations et etude du mecanisme de l’isomerisation ZE. Tetrahedron 33, 2535–2542 (1977).

  30. 30.

    Bakhmutov, V. I. et al. A dynamic NMR study of Z,E‐isomerization in solutions of indolyl‐substituted α‐nitroacrylates. Org. Magn. Reson. 11, 308–312 (1978).

  31. 31.

    Appenroth, K., Reichenbächer, M. & Paetzold, R. Thermochromism and photochromism of aryl-substituted acyclic azines.Tetrahedron 37, 569–573 (1981).

  32. 32.

    Kirste, K. & Rademacher, P. Rotation and inversion in nitrosamines. J. Mol. Struct. 73, 171–180 (1981).

  33. 33.

    Sammes, M. P. The effect of salt formation on structure and charge distribution in imines. Part 4. Energy barriers to isomerisation about the C–N bond in 2,6-dimethyl-4-aryliminopyrans and their salts: solvent and substituent effects, and evidence for isomerisation mechanisms. J. Chem. Soc., Perkin Trans. 2, 1501–1507 (1981).

  34. 34.

    Kawada, Y. & Iwamura, H. Bis(4-chloro-1-triptycyl) ether. Separation of a pair of phase isomers of labeled bevel gears. J. Am. Chem. Soc. 103, 958–960 (1981).

  35. 35.

    Gustav, K., Vettermann, S. & Birner, P. Quantum chemical studies on colour and stereodynamics of acyclic azines. Part IX. The coupled N–N rotation/N inversion mechanism for the thermal (E,Z) isomerization of benzaldazine. THEOCHEM 88, 249–253 (1982).

  36. 36.

    Kawada, Y. & Iwamura, H. Correlated rotation in bis(9-triptycyl)methanes and bis(9-triptycyl) ethers. Separation and interconversion of the phase isomers of labeled bevel gears. J. Am. Chem. Soc. 105, 1449–1459 (1983).

  37. 37.

    Cunningham, I. D. & Hegarty, A. F. Acid, base, and uncatalysed isomerisation of Z- to E-amidine. A mechanistic study. J. Chem. Soc., Perkin Trans. 2, 537–541 (1986).

  38. 38.

    Frenna, V., Buscemi, S., Spinelli, D. & Consiglio, G. A kinetic study on the base-catalysed EZ isomerization of some arylhydrazones of 3-benzoyl-5-phenyl-1,2,4-oxadiazole: effect of the substituents in the arylhydrazone moiety. J. Chem. Soc., Perkin Trans. 2, 215–221 (1990).

  39. 39.

    Gáplovský, A., Donovalová, J., Lacová, M., Mračnová, R. & El-Shaaer, H. M. The photochemical behaviour of 6-X-4H-3(bicyclo[2.2.1]-5-heptene-2,3-dicarboximidoiminomethyl)-4-chromones. Photochromism and thermochromism. J. Photochem. Photobiol., A 136, 61–65 (2000).

  40. 40.

    Sung, K. N-substituent effects on the stability of ketenimines. J. Chem. Soc., Perkin Trans. 2, 847–852 (2000).

  41. 41.

    Klika, K. D. et al. Configuration and E/Z interconversion mechanism of O(S)-allyl-S(O)-methyl-N-(acridin-9-yl)-iminothiocarbonate. Magn. Reson. Chem. 43, 380–388 (2005).

  42. 42.

    Pirozhenko, V. V., Rozhenko, A. B., Avdeenko, A. P., Konovalova, S. A. & Santalova, A. A. Z,E-isomerization mechanism for N-arylthio-1,4-benzoquinonimines: DNMR and DFT investigations. Magn. Reson. Chem. 46, 811–817 (2008).

  43. 43.

    Landge, S. M. et al. Isomerization mechanism in hydrazone-based rotary switches: Lateral shift, rotation, or tautomerization? J. Am. Chem. Soc. 133, 9812–9823 (2011).

  44. 44.

    Luo, Y. et al. Cistrans isomerisation of substituted aromatic imines: a comparative experimental and theoretical study. ChemPhysChem 12, 2311–2321 (2011).

  45. 45.

    Greb, L., Eichhöfer, A. & Lehn, J. M. Synthetic molecular motors: thermal N inversion and directional photoinduced C=N bond rotation of camphorquinone imines. Angew. Chem. Int. Ed. 54, 14345–14348 (2015).

  46. 46.

    Belcher, W. J., Boyd, P. D. W., Brothers, P. J., Liddell, M. J. & Rickard, C. E. F. J. Am. Chem. Soc. 116, 8416–8417 (1994).

  47. 47.

    Belcher, W. J., Breede, M., Brothers, P. J. & Rickard, C. E. F. The porphyrin as a binucleating ligand: preparation and crystal structure of a porphyrin complex containing a coordinated B2O2 ring. Angew. Chem. Int. Ed. 37, 1112–1114 (1998).

  48. 48.

    Brothers, P. J. Organometallic chemistry of main group porphyrin complexes. Adv. Organomet. Chem. 48, 289–295 (2001).

  49. 49.

    Brothers, P. J. Recent developments in the coordination chemistry of porphyrin complexes containing non-metallic and semi-metallic elements. J. Porphyr. Phthalocyanines 6, 259–267 (2002).

  50. 50.

    Köhler, T.et al. Octaethylporphyrin and expanded porphyrin complexes containing coordinated BF2 groups. Chem. Commun.1060–1061 (2004).

  51. 51.

    Albrett, A. M., Boyd, P. D. W., Clark, G. R., Gonzalez, E. & Brothers, P. J. Reductive coupling and protonation leading to diboron corroles with a B–H–B bridge. Dalton Trans. 39, 4032–4034 (2010).

  52. 52.

    Belcher, W. J. et al. Porphyrin complexes containing coordinated BOB groups: synthesis, chemical reactivity and the structure of [BOB(tpClpp)]2+. Dalton Trans., 1602–1614 (2008).

  53. 53.

    Brothers, P. J. Boron complexes of porphyrins and related polypyrrole ligands: unexpected chemistry for both boron and the porphyrin. Chem. Commun. 2090–2102 (2008).

  54. 54.

    Albrett, A. Synthesis of Boron Corrole Complexes. PhD thesis, Univ. Auckland (2009).

  55. 55.

    Brothers, P. J. Boron complexes of pyrrolyl ligands. Inorg. Chem. 50, 12374–12386 (2011).

  56. 56.

    Albrett, A. M. et al. Mono- and diboron corroles: factors controlling stoichiometry and hydrolytic reactivity. Inorg. Chem. 53, 5486–5493 (2014).

  57. 57.

    Weiss, A., Hodgson, M. C., Boyd, P. D. W., Siebert, W. & Brothers, P. J. Diboryl and diboranyl porphyrin complexes: synthesis, structural motifs, and redox chemistry: diborenyl porphyrin or diboranyl isophlorin? Chem. Eur. J. 13, 5982–5993 (2007).

  58. 58.

    Albrett, A. M. et al. Corrole as a binucleating ligand: preparation, molecular structure and density functional theory study of diboron corroles. J. Am. Chem. Soc. 130, 2888–2889 (2008).

  59. 59.

    Albrett, A. M., Conradie, J., Ghosh, A. & Brothers, P. J. DFT survey of monoboron and diboron corroles: regio- and stereochemical preferences for a constrained, low-symmetry macrocycle. Dalton Trans. 4464–4473 (2008).

  60. 60.

    Crossley, M. J., Sintic, P. J., Walton, R. & Reimers, J. R. Synthesis and physical properties of biquinoxalinyl bridged bis-porphyrins: models for aspects of photosynthetic reaction centres. Org. Biomol. Chem. 1, 2777–2787 (2003).

  61. 61.

    Kadish, K. M. et al. Quinoxalino[2,3-b′]porphyrins behave as π-expanded porphyrins upon one-electron reduction: broad control of the degree of delocalization through substitution at the macrocycle periphery. J. Phys. Chem. B 111, 8762–8774 (2007).

  62. 62.

    Sintic, P. J. et al. Control of the site and potential of reduction and oxidation processes in π-expanded quinoxalinoporphyrins. Phys. Chem. Chem. Phys. 10, 268–280 (2008).

  63. 63.

    Hartshorn, R. The red book – nomenclature of inorganic chemistry. IUPAC Recommendations 2005. Chem. Int. 29, 14–16 (2007).

  64. 64.

    Dixon, H. B. F. et al. Nomenclature of tetrapyrroles. Pure Appl. Chem. 59, 779–832 (1987).

  65. 65.

    Goerigk, L. & Sharma, R. The INV24 test set: how well do quantum-chemical methods describe inversion and racemization barriers? Can. J. Chem. 94, 1133–1143 (2016).

  66. 66.

    Krausz, E. Selective and differential optical spectroscopies in photosynthesis. Photosynth. Res. 116, 411–426 (2013).

  67. 67.

    Scott, D. R. S. & Allison, J. B. Solvent glasses for low temperature spectroscopic studies. J. Phys. Chem. 66, 561–562 (1962).

  68. 68.

    Reimers, J. R. & Krausz, E. An analytical data inversion method for magnetic circular dichroism spectra dominated by the ‘B-term’. Phys. Chem. Chem. Phys. 16, 2315–2322 (2014).

  69. 69.

    Sendt, K. et al. Switchable electronic coupling in oligoporphyrin molecular wires examined through the measurement and assignment of electronic absorption spectra. J. Am. Chem. Soc. 124, 9299–9309 (2002).

  70. 70.

    Becke, A. D. Density-functional thermochemistry. III. The role of exact exchange. J. Chem. Phys. 98, 5648–5652 (1993).

  71. 71.

    Yanai, T., Tew, D. P. & Handy, N. C. A new hybrid exchange-correlation functional using the Coulomb-attenuating method (CAM-B3LYP). Chem. Phys. Lett. 393, 51–57 (2004).

  72. 72.

    Kobayashi, R. & Amos, R. D. The application of CAM-B3LYP to the charge-transfer band problem of the zincbacteriochlorin–bacteriochlorin complex. Chem. Phys. Lett. 420, 106–109 (2006).

  73. 73.

    Cai, Z.-L., Crossley, M. J., Reimers, J. R., Kobayashi, R. & Amos, R. D. Density-functional theory for charge-transfer: the nature of the N-bands of porphyrins and chlorophylls revealed through CAM-B3LYP, CASPT2, and SAC-CI calculations. J. Phys. Chem. B 110, 15624–15632 (2006).

  74. 74.

    Chai, J.-D. & Head-Gordon, M. Long-range corrected hybrid density functionals with damped atom-atom dispersion corrections. Phys. Chem. Chem. Phys. 10, 6615–6620 (2008).

  75. 75.

    Foresman, J. B., Head-Gordon, M., Pople, J. A. & Frisch, M. J. towards a systematic molecular orbital theory for excited states. J. Phys. Chem. 96, 135 (1992).

  76. 76.

    Frisch, M. J. et al. Gaussian 09, Revision D.01 (Gaussian, 2009).

  77. 77.

    Goerigk, L. & Grimme, S. A thorough benchmark of density functional methods for general main group thermochemistry, kinetics, and noncovalent interactions. Phys. Chem. Chem. Phys. 13, 6670–6688 (2011).

  78. 78.

    Tomasi, J., Mennucci, B. & Cammi, R. Quantum mechanical continuum solvation models. Chem. Rev. 105, 2999–3093 (2005).

  79. 79.

    Floris, F. M., Tomasi, J. & Pascual Ahuir, J. L. Dispersion and repulsion contributions to the solvation energy: refinements to a simple computational model in the continuum approximation. J. Comput. Chem. 12, 784–791 (1991).

  80. 80.

    Wolinski, K., Hinton, J. F. & Pulay, P. Efficient implementation of the gauge-independent atomic orbital method for NMR chemical shift calculations. J. Am. Chem. Soc. 112, 8251–8260 (1990).

  81. 81.

    Kobayashi, R. & Reimers, J. R. Free energies for the coordination of ligands to the magnesium of chlorophyll-a in solvents. Mol. Phys. 16, 928–932 (2015).

  82. 82.

    Reimers, J. R. et al. Assignment of the Q-bands of the chlorophylls: coherence loss via Qx–Qy mixing. Sci. Rep. 3, 2761 (2013).

  83. 83.

    Werner, H.-J. et al. MOLPRO, Version 2015.1, A Package of Ab Initio Programs (Univ. Birmingham, 2015).

  84. 84.

    Dunning, T. H. Jr Gaussian basis sets for use in correlated molecular calculations I. The atoms boron through neon and hydrogen. J. Chem. Phys. 90, 1007 (1989).

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Acknowledgements

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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Affiliations

  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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Contributions

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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