Odd–even alternations in helical propensity of a homologous series of hydrocarbons


Odd and even homologues of some n-alkane-based systems are known to exhibit notably different trends in solid-state properties; a well-known illustration is the zigzag plot of their melting point versus chain length. Odd–even effects in the solid state often arise from intermolecular interactions that involve fully extended molecules. These effects have also been observed in less condensed phases, such as self-assembled monolayers; however, the origins of these effects in such systems can be difficult to determine. Here we combined NMR and computational analysis to show that all-syn contiguously methyl-substituted hydrocarbons, with chain lengths from C6 to C11, exhibit a dramatic odd–even effect in helical propensity. The even- and odd-numbered hydrocarbons populate regular and less-controlled helical conformations, respectively. This knowledge will guide the design of helical hydrocarbons as rigid scaffolds or as hydrophobic components in soft materials.

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Fig. 1: Known examples of odd–even effects associated with bulk properties.
Fig. 2: Previously reported iterative homologation of boronic esters and conformational control13.
Fig. 3: Relationships between chain length, sequence of dihedral angles and conformational behaviour.
Fig. 4: Synthesis and conformational analysis.

Data availability

Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 1908685 (14), 1908684 (18), 1908686 (C10), 1935492 (31), 1935491 (32) and 1935490 (36). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. All other data supporting the findings of this study are available within the article and its Supplementary Information, or from the corresponding author upon reasonable request.

Code availability

The Python script used in the computational study is included in the Supplementary Information file.


  1. 1.

    Baeyer, A. Ueber regelmässigkeiten im schmelzpunkt homologer verbindungen. Ber. Dtsch. Chem. Ges. 10, 1286–1288 (1877).

    Article  Google Scholar 

  2. 2.

    Boese, R., Weiss, H.-C. & Bläser, D. The melting point alternation in the short-chain n-alkanes: single-crystal X-ray analyses of propane at 30 K and of n-butane to n-nonane at 90 K. Angew. Chem. Int. Ed. 38, 988–992 (1999).

    Article  CAS  Google Scholar 

  3. 3.

    Bond, A. D. On the crystal structures and melting point alternation of the n-alkyl carboxylic acids. New J. Chem. 28, 104–114 (2004).

    Article  CAS  Google Scholar 

  4. 4.

    Tao, F. & Bernasek, S. L. Understanding odd−even effects in organic self-assembled monolayers. Chem. Rev. 107, 1408–1453 (2007).

    Article  CAS  Google Scholar 

  5. 5.

    Newcomb, L. B. et al. Odd–even effect in the hydrophobicity of n-alkanethiolate self-assembled monolayers depends upon the roughness of the substrate and the orientation of the terminal moiety. Langmuir 30, 11985–11992 (2014).

    Article  CAS  Google Scholar 

  6. 6.

    Baghbanzadeh, M. et al. Odd–even effects in charge transport across n-alkanethiolate-based SAMs. J. Am. Chem. Soc. 136, 16919–16925 (2014).

    Article  CAS  Google Scholar 

  7. 7.

    Jiang, L., Sangeeth, C. S. S. & Nijhuis, C. A. The origin of the odd–even effect in the tunneling rates across EGaIn junctions with self-assembled monolayers (SAMs) of n-alkanethiolates. J. Am. Chem. Soc. 137, 10659–10667 (2015).

    Article  CAS  Google Scholar 

  8. 8.

    Chen, J., Chang, B., Oyola-Reynoso, S., Wang, Z. & Thuo, M. Quantifying gauche defects and phase evolution in self-assembled monolayers through sessile drops. ACS Omega 2, 2072–2084 (2017).

    Article  CAS  Google Scholar 

  9. 9.

    Ramin, L. & Jabbarzadeh, A. Odd–even effects on the structure, stability, and phase transition of alkanethiol self-assembled monolayers. Langmuir 27, 9748–9759 (2011).

    Article  CAS  Google Scholar 

  10. 10.

    Chen, J. et al. Understanding interface (odd–even) effects in charge tunneling using a polished EGaIn electrode. Phys. Chem. Chem. Phys. 20, 4864–4878 (2018).

    Article  CAS  Google Scholar 

  11. 11.

    Xie, C. et al. Stretch-Induced coil–helix transition in isotactic polypropylene: a molecular dynamics simulation. Macromolecules 51, 3994–4002 (2018).

    Article  CAS  Google Scholar 

  12. 12.

    Stymiest, J. L., Dutheuil, G., Mahmood, A. & Aggarwal, V. K. Lithiated carbamates: chiral carbenoids for iterative homologation of boranes and boronic esters. Angew. Chem. Int. Ed. 46, 7491–7494 (2007).

    Article  CAS  Google Scholar 

  13. 13.

    Burns, M. et al. Assembly-line synthesis of organic molecules with tailored shapes. Nature 513, 183–188 (2014).

    Article  CAS  Google Scholar 

  14. 14.

    Hoffmann, R. W. Flexible molecules with defined shape—conformational design. Angew. Chem. Int. Ed. 31, 1124–1134 (1992).

    Article  Google Scholar 

  15. 15.

    Tsuzuki, S. et al. Investigation of intramolecular interactions in n-alkanes. Cooperative energy increments associated with GG and GTG′ sequences. J. Am. Chem. Soc. 113, 4665–4671 (1991).

    Article  CAS  Google Scholar 

  16. 16.

    Hoffmann, R. W., Stahl, M., Schopfer, U. & Frenking, G. Conformation design of hydrocarbon backbones: a modular approach. Chem. Eur. J. 4, 559–566 (1998).

    Article  CAS  Google Scholar 

  17. 17.

    Wechsel, R., Raftery, J., Cavagnat, D., Guichard, G. & Clayden, J. The meso helix: symmetry and symmetry-breaking in dynamic foldamers with reversible hydrogen-bond polarity. Angew. Chem. Int. Ed. 55, 9657–9661 (2016).

    Article  CAS  Google Scholar 

  18. 18.

    Tomsett, M. et al. A tendril perversion in a helical oligomer: trapping and characterizing a mobile screw-sense reversal. Chem. Sci. 8, 3007–3018 (2017).

    Article  CAS  Google Scholar 

  19. 19.

    Wang, Y., Noble, A., Myers, E. L. & Aggarwal, V. K. Enantiospecific alkynylation of alkylboronic esters. Angew. Chem. Int. Ed. 55, 4270–4274 (2016).

    Article  CAS  Google Scholar 

  20. 20.

    Morgan, J. B., Miller, S. P. & Morken, J. P. Rhodium-catalyzed enantioselective diboration of simple alkenes. J. Am. Chem. Soc. 125, 8702–8703 (2003).

    Article  CAS  Google Scholar 

  21. 21.

    Trudeau, S., Morgan, J. B., Shrestha, M. & Morken, J. P. Rh-catalyzed enantioselective diboration of simple alkenes: reaction development and substrate scope. J. Org. Chem. 70, 9538–9544 (2005).

    Article  CAS  Google Scholar 

  22. 22.

    Izumi, H., Yamagami, S., Futamura, S., Nafie, L. A. & Dukor, R. K. Direct observation of odd−even effect for chiral alkyl alcohols in solution using vibrational circular dichroism spectroscopy. J. Am. Chem. Soc. 126, 194–198 (2004).

    Article  CAS  Google Scholar 

  23. 23.

    Lüttschwager, N. O. B., Wassermann, T. N., Mata, R. A. & Suhm, M. A. The last globally stable extended alkane. Angew. Chem. Int. Ed. 52, 463–466 (2013).

    Article  CAS  Google Scholar 

  24. 24.

    Yang, K. et al. Dynamic odd–even effect in liquid n-alkanes near their melting points. Angew. Chem. Int. Ed. 55, 14090–14095 (2016).

    Article  CAS  Google Scholar 

  25. 25.

    Liu, B. et al. Polyfluorene (PF) single-chain conformation, β conformation, and its stability and chain aggregation by side-chain length change in the solution dynamic process. J. Phys. Chem. C 122, 14814–14826 (2018).

    Article  CAS  Google Scholar 

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We thank H2020 ERC (670668) for financial support. We thank N. Pridmore and H. Sparkes for assistance with the X-ray analysis, M. Davey for useful discussions about VCD and W. Gerrard for his contribution to data processing. S.Z. thanks the EPSRC Bristol Chemical Synthesis Doctoral Training Centre for a studentship (EP/L015366/1). We thank S. Varga (Hungarian Academy of Sciences Research Centre for Natural Sciences) for supporting the VCD measurements. The work at Eötvös University was completed within the framework of the ELTE Excellence Program (1783-3/2018/FEKUTSTRAT) supported by the Hungarian Ministry of Human Capacities (EMMI).

Author information




J.A.P. and S.Z. contributed equally to this work. V.K.A., C.P.B. and E.L.M. designed the project. J.A.P. conducted and designed the experiments and analysed the data. S.Z. conducted and designed the computational studies and NMR experiments. M.B. and G.T. performed the VCD experiments and analysed the data. J.A.P., S.Z., E.L.M., C.P.B. and V.K.A. wrote the manuscript.

Corresponding authors

Correspondence to Craig P. Butts or Eddie L. Myers or Varinder K. Aggarwal.

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Competing interests

The authors declare no competing interests.

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Supplementary information

Supplementary Information

Experimental procedures, experimental data, compound characterization data, computational procedures, NMR procedures, VCD data, NMR spectra and X-ray crystallography data.

XYZ coordinates

Instructions and Excel document including one worksheet for each compound studied computationally. Each worksheet contains the xyz coordinates of all conformers of that particular compound.

Crystallographic data

CIF for compound 14; CCDC reference 1908685.

Crystallographic data

CIF for compound 18; CCDC reference 1908684.

Crystallographic data

CIF for compound C10; CCDC reference 1908686.

Crystallographic data

CIF for compound 31; CCDC reference 1935492.

Crystallographic data

CIF for compound 32; CCDC reference 1935491.

Crystallographic data

CIF for compound 36; CCDC reference 1935490.

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Pradeilles, J.A., Zhong, S., Baglyas, M. et al. Odd–even alternations in helical propensity of a homologous series of hydrocarbons. Nat. Chem. 12, 475–480 (2020). https://doi.org/10.1038/s41557-020-0429-0

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