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Potential enthalpic energy of water in oils exploited to control supramolecular structure

Naturevolume 558pages100103 (2018) | Download Citation


Water directs the self-assembly of both natural1,2 and synthetic3,4,5,6,7,8,9 molecules to form precise yet dynamic structures. Nevertheless, our molecular understanding of the role of water in such systems is incomplete, which represents a fundamental constraint in the development of supramolecular materials for use in biomaterials, nanoelectronics and catalysis10. In particular, despite the widespread use of alkanes as solvents in supramolecular chemistry11,12, the role of water in the formation of aggregates in oils is not clear, probably because water is only sparingly miscible in these solvents—typical alkanes contain less than 0.01 per cent water by weight at room temperature13. A notable and unused feature of this water is that it is essentially monomeric14. It has been determined previously15 that the free energy cost of forming a cavity in alkanes that is large enough for a water molecule is only just compensated by its interaction with the interior of the cavity; this cost is therefore too high to accommodate clusters of water. As such, water molecules in alkanes possess potential enthalpic energy in the form of unrealized hydrogen bonds. Here we report that this energy is a thermodynamic driving force for water molecules to interact with co-dissolved hydrogen-bond-based aggregates in oils. By using a combination of spectroscopic, calorimetric, light-scattering and theoretical techniques, we demonstrate that this interaction can be exploited to modulate the structure of one-dimensional supramolecular polymers.

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  1. 1.

    Nagornova, N. S., Rizzo, T. R. & Boyarkin, O. V. Interplay of intra- and intermolecular H-bonding in a progressively solvated macrocyclic peptide. Science 336, 320–323 (2012).

  2. 2.

    Umena, Y., Kawakami, K., Shen, J. R. & Kamiya, N. Crystal structure of oxygen-evolving photosystem II at a resolution of 1.9 Å. Nature 473, 55–60 (2011).

  3. 3.

    Berl, V., Huc, I., Khoury, R. G., Krische, M. J. & Lehn, J. M. Interconversion of single and double helices formed from synthetic molecular strands. Nature 407, 720–723 (2000).

  4. 4.

    Hirschberg, J. H. K. K. et al. Helical self-assembled polymers from cooperative stacking of hydrogen-bonded pairs. Nature 407, 167–170 (2000).

  5. 5.

    Hartgerink, J. D., Beniash, E. & Stupp, S. I. Self-assembly and mineralization of peptide-amphiphile nanofibers. Science 294, 1684–1688 (2001).

  6. 6.

    Jain, S. & Bates, F. S. On the origins of morphological complexity in block copolymer surfactants. Science 300, 460–464 (2003).

  7. 7.

    Johnson, R. S., Yamazaki, T., Kovalenko, A. & Fenniri, H. Molecular basis for water-promoted supramolecular chirality inversion in helical rosette nanotubes. J. Am. Chem. Soc. 129, 5735–5743 (2007).

  8. 8.

    Appel, E. A. et al. Supramolecular cross-linked networks via host-guest complexation with cucurbit[8]uril. J. Am. Chem. Soc. 132, 14251–14260 (2010).

  9. 9.

    Arazoe, H. et al. An autonomous actuator driven by fluctuations in ambient humidity. Nat. Mater. 15, 1084–1089 (2016).

  10. 10.

    Aida, T., Meijer, E. W. & Stupp, S. I. Functional supramolecular polymers. Science 335, 813–817 (2012).

  11. 11.

    De Greef, T. F. et al. Supramolecular polymerization. Chem. Rev. 109, 5687–5754 (2009).

  12. 12.

    Liu, M., Zhang, L. & Wang, T. Supramolecular chirality in self-assembled systems. Chem. Rev. 115, 7304–7397 (2015).

  13. 13.

    Riddick, J. A., Bunger, W. B. & Sakano, T. K. Organic Solvents, Physical Properties and Methods of Purification. (John Wiley & Sons, New York, 1986).

  14. 14.

    Christian, S. D., Taha, A. A. & Gash, B. W. Molecular complexes of water in organic solvents and in the vapour phase. Q. Rev. Chem. Soc. 24, 20–36 (1970).

  15. 15.

    Wolfenden, R. & Radzicka, A. On the probability of finding a water molecule in a nonpolar cavity. Science 265, 936–937 (1994).

  16. 16.

    Fitié, C. F. et al. Polar switching in trialkylbenzene-1,3,5-tricarboxamides. J. Phys. Chem. B 116, 3928–3937 (2012).

  17. 17.

    Smulders, M. M., Schenning, A. P. & Meijer, E. W. Insight into the mechanisms of cooperative self-assembly: the “sergeants-and-soldiers” principle of chiral and achiral C3-symmetrical discotic triamides. J. Am. Chem. Soc. 130, 606–611 (2008).

  18. 18.

    García, F. et al. The influence of π-conjugated moieties on the thermodynamics of cooperatively self-assembling tricarboxamides. Chem. Commun. 49, 8674–8676 (2013).

  19. 19.

    Mohr, S. C., Wilk, W. D. & Barrow, G. M. The association of water with bases and anions in an inert solvent. J. Am. Chem. Soc. 87, 3048–3052 (1965).

  20. 20.

    Iwamoto, R. Infrared and near-infrared study of the interaction of amide C=O with water in ideally inert medium. J. Phys. Chem. A 114, 7398–7407 (2010).

  21. 21.

    Sorrenti, A., Leira-Iglesias, J., Markvoort, A. J., de Greef, T. F. A. & Hermans, T. M. Non-equilibrium supramolecular polymerization. Chem. Soc. Rev. 46, 5476–5490 (2017).

  22. 22.

    Zhao, D. & Moore, J. S. Nucleation-elongation: a mechanism for cooperative supramolecular polymerization. Org. Biomol. Chem. 1, 3471–3491 (2003).

  23. 23.

    Venkata Rao, K., Miyajima, D., Nihonyanagi, A. & Aida, T. Thermally bisignate supramolecular polymerization. Nat. Chem. 9, 1133–1139 (2017).

  24. 24.

    Gilli, G., Bellucci, F., Ferretti, V. & Bertolasi, V. Evidence for resonance-assisted hydrogen bonding from crystal-structure correlations on the enol form of the β-diketone fragment. J. Am. Chem. Soc. 111, 1023–1028 (1989).

  25. 25.

    Filot, I. A. W. et al. Understanding cooperativity in hydrogen-bond-induced supramolecular polymerization: a density functional theory study. J. Phys. Chem. B 114, 13667–13674 (2010).

  26. 26.

    Chandler, D. Interfaces and the driving force of hydrophobic assembly. Nature 437, 640–647 (2005).

  27. 27.

    Biedermann, F., Nau, W. M. & Schneider, H. J. The hydrophobic effect revisited—studies with supramolecular complexes imply high-energy water as a noncovalent driving force. Angew. Chem. Int. Ed. 53, 11158–11171 (2014).

  28. 28.

    Lassettre, E. N. The hydrogen bond and association. Chem. Rev. 20, 259–303 (1937).

  29. 29.

    Louhichi, A., Jacob, A. R., Bouteiller, L. & Vlassopoulos, D. Humidity affects the viscoelastic properties of supramolecular living polymers. J. Rheol. 61, 1173–1182 (2017).

  30. 30.

    Adelizzi, B., Filot, I. A. W., Palmans, A. R. A. & Meijer, E. W. Unravelling the pathway complexity in conformationally flexible N-centered triarylamine trisamides. Chem. Eur. J. 23, 6103–6110 (2017).

  31. 31.

    Mazik, M. & König, A. Recognition properties of an acyclic biphenyl-based receptor toward carbohydrates. J. Org. Chem. 71, 7854–7857 (2006).

  32. 32.

    Suthagar, K., Watson, A. J., Wilkinson, B. L. & Fairbanks, A. J. Synthesis of arabinose glycosyl sulfamides as potential inhibitors of mycobacterial cell wall biosynthesis. Eur. J. Med. Chem. 102, 153–166 (2015).

  33. 33.

    Brunsveld, L. et al. Chiral amplification in columns of self-assembled N,N′,N″-tris((S)-3,7-dimethyloctyl)benzene-1,3,5-tricarboxamide in dilute solution. Chem. Lett. 29, 292–293 (2000).

  34. 34.

    Boekhoven, J. et al. Dissipative self-assembly of a molecular gelator by using a chemical fuel. Angew. Chem. Int. Ed. 49, 4825–4828 (2010).

  35. 35.

    Christian, S. D., Affsprung, H. E., Johnson, J. R. & Worley, J. D. Control and measurement of water activity. J. Chem. Educ. 40, 419–421 (1963).

  36. 36.

    van Gorp, J. J., Vekemans, J. A. J. M. & Meijer, E. W. C 3-symmetrical supramolecular architectures: fibers and organic gels from discotic trisamides and trisureas. J. Am. Chem. Soc. 124, 14759–14769 (2002).

  37. 37.

    Markvoort, A. J., ten Eikelder, H. M., Hilbers, P. A., de Greef, T. F. & Meijer, E. W. Theoretical models of nonlinear effects in two-component cooperative supramolecular copolymerizations. Nat. Commun. 2, 509 (2011).

  38. 38.

    Aloi, A. et al. Imaging nanostructures by single-molecule localization microscopy in organic solvents. J. Am. Chem. Soc. 138, 2953–2956 (2016).

  39. 39.

    Aloi, A., Vilanova, N., Albertazzi, L. & Voets, I. K. iPAINT: a general approach tailored to image the topology of interfaces with nanometer resolution. Nanoscale 8, 8712–8716 (2016).

  40. 40.

    Schreurs, A. M. M., Xian, X. & Kroon-Batenburg, L. M. J. EVAL15: a diffraction data integration method based on ab initio predicted profiles. J. Appl. Crystallogr. 43, 70–82 (2010).

  41. 41.

    Sheldrick, G. M. SADABS (Univ. Göttingen, 2008).

  42. 42.

    Sheldrick, G. M. SHELXT - integrated space-group and crystal-structure determination. Acta Crystallogr. A 71, 3–8 (2015).

  43. 43.

    Sheldrick, G. M. Crystal structure refinement with SHELXL. Acta Crystallogr. C 71, 3–8 (2015).

  44. 44.

    Spek, A. L. Structure validation in chemical crystallography. Acta Crystallogr. D 65, 148–155 (2009).

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This project received funding from the European Union’s Horizon 2020 research and innovation program (no. 705701) and the Dutch Ministry of Education, Culture and Science’s Gravitation program (no. 024.001.035). The X-ray diffractometer was financed by the Netherlands Organization for Scientific Research. N.J.V.Z. acknowledges M. L. Ślęczkowski for synthesizing the chiral amine precursor for 1, B. F. M. de Waal for assistance with Karl Fischer titrations and R. A. A. Bovee for performing MALDI–TOF MS measurements. We also thank S. C. J. Meskers, R. J. M. Nolte and A. J. Markvoort for discussions.

Reviewer information

Nature thanks C. Hunter, D. Miyajima and D. Pantos for their contribution to the peer review of this work.

Author information


  1. Institute for Complex Molecular Systems, Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, Eindhoven, The Netherlands

    • Nathan J. Van Zee
    • , Beatrice Adelizzi
    • , Mathijs F. J. Mabesoone
    • , Xiao Meng
    • , Antonio Aloi
    • , R. Helen Zha
    • , Ivo A. W. Filot
    • , Anja R. A. Palmans
    •  & E. W. Meijer
  2. Laboratory of Self-Organizing Soft Matter, Eindhoven University of Technology, Eindhoven, The Netherlands

    • Antonio Aloi
  3. Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands

    • Martin Lutz
  4. Inorganic Materials Chemistry, Eindhoven University of Technology, Eindhoven, The Netherlands

    • Ivo A. W. Filot


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N.J.V.Z. conceived the project and designed the experiments. N.J.V.Z., B.A., X.M., R.H.Z. and A.A. performed the experiments and analysed the data. M.F.J.M. and I.A.W.F. performed the mathematical simulations and density functional theory calculations, respectively. M.L. determined the crystal structure of 2. N.J.V.Z., M.F.J.M., A.A. and I.A.W.F. wrote the manuscript. A.R.A.P. and E.W.M. supervised the research.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to E. W. Meijer.

Extended data figures and tables

  1. Extended Data Fig. 1 Bulk characterization of 1.

    a, DSC trace of 1 (cooling in blue, second heating in red). b, Polarized optical microscopy image of 1 with crossed polarizers at 135 °C after cooling from the isotropic melt. c, Wide-angle X-ray scattering trace of bulk 1 at room temperature (top) with a schematic of the hexagonal columnar morphology (bottom left) and tabulated parameters (bottom right). d, CD signal (top) and absorbance (bottom) of a thin film of 1 at 20 °C. e, FTIR spectrum of bulk 1 at 20 °C after cooling from the isotropic melt. f, Comparison of the FTIR spectra of bulk 1 after cooling from the isotropic melt and A ([1] = 2.0 mM in dry MCH, labels in cm−1).

  2. Extended Data Fig. 2 Super-resolution fluorescence and AFM images of 1.

    a, Supramolecular fibres of 1 stained with Cage-552 photoactivatable dye imaged by super-resolution fluorescence microscopy (left) and corresponding thickness analysis (right). The indicated zone in the microscopy image is depicted in Fig. 1b. A discussion of the thickness analysis and a comparison to fibres of 6 is provided in the Supplementary Information. b, Supramolecular fibres of 1 imaged by AFM in non-contact tapping mode. The indicated zone is depicted in Fig. 1c.

  3. Extended Data Fig. 3 Removal of water from aggregates of 1 to effect helicity transitions.

    a, Schematic of experimental design. The CD spectrometer was purged with nitrogen at a rate of 20 l min−1. b, CD signal (top) and absorbance (bottom) at 258 nm as a 30 µM solution of 1 is dried over 100 min in the sample holder of the CD spectrometer. All water content measurements are reported as mean ± s.d. (n = 2).

  4. Extended Data Fig. 4 van ’t Hoff analyses.

    a, van ’t Hoff plot of ln(Ke) versus 1/Te (left) with tabulated Te data (right). b, van ’t Hoff plot of ln(Khyd,A) versus 1/TAB. The points represent ln(Khyd,A) calculated using the mean of the water content determined for each respective measurement. The error bars correspond to the spread of ln(Khyd,A) as a result of the experimental uncertainty of each respective water content measurement. c, van ’t Hoff plot of ln(Khyd,B) versus 1/TBC. The points represent ln(Khyd,B) calculated using the mean of the water content determined for each respective measurement. The error bars correspond to the spread of ln(Khyd,B) as a result of the experimental uncertainty of each respective water content measurement. d, Determination of TAB and TBC from the second derivative of the corresponding VT-CD curves presented in Fig. 1f (labels in °C).

  5. Extended Data Fig. 5 Cooling and heating experiments using VT-CD spectroscopy.

    The CD intensity was monitored at 258 nm while cooling from 95 °C to −5 °C and then immediately heating back to 95 °C with scanning rates of 15 (left), 30 (middle) and 60 °C h−1 (right). Samples were prepared with as-received MCH ([1] = 30 µM, [H2O] = 35 ± 2 p.p.m.).

  6. Extended Data Fig. 6 Heating experiments with aggregates of 1.

    A 0.51 µM solution of 1 in as-received MCH was characterized by VT-CD spectroscopy (top), micro-DSC (middle) and light scattering (bottom, mean ± s.d. (n = 5) are shown). In the micro-DSC plot, only the endothermic transitions corresponding to BA with scan rates of 15 and 30 °C h−1 had baselines suitable for integration (labels in kJ (mol 1)−1).

  7. Extended Data Fig. 7 Crystal structure of 2.

    a, Chemical structure of 2. b, Displacement ellipsoid plot (50% probability level) of 2 in the crystal. C–H hydrogen atoms and chloroform solvent molecules are omitted for clarity. Only one of two independent molecules is shown. The other independent molecule is located on an inversion centre. c, Packing of 2 in the crystal. The two independent molecules are shown in black and red, respectively. Hydrogen atoms and chloroform solvent molecules are omitted for clarity. The structure shows pseudo-translational symmetry in the b-direction.

  8. Extended Data Fig. 8 Molecular model of water binding to an aggregate of biphenyl tetracarboxamide molecules.

    a, Chemical structure of 3. b, Molecular models based on density functional theory calculations for the incorporation of four water molecules into a hexameric aggregate of 3. Hydrogen atoms, apart from those engaged in hydrogen bonding, are omitted for clarity. The structures are colour coded as follows: hydrogen bond, dashed lines; carbon, black; oxygen, red; nitrogen, blue; water molecules, green.

  9. Extended Data Fig. 9 The influence of water content on the self-assembly of 6 in MCH.

    a, CD signal (top), ultraviolet absorbance (middle) and light-scattering counts (bottom, mean ± s.d. (n = 5) are shown) acquired while cooling solutions of 6 in wet, as-received or dry MCH. b, Typical AFM picture (left) and height profiles (right) of a sample of 6 (30 µM in wet MCH) that was drop-cast on mica in a water-saturated environment. The indicated zone is depicted in Fig. 4d. c, Typical AFM picture (left) and height profiles (right) of a sample of 6 (30 µM in dry MCH) that was drop-cast on mica under dry conditions in a glovebox. The indicated zone is depicted in Fig. 4e.

Supplementary information

  1. Supplementary Information

    This file contains Supplementary Figures 1-13 and Supplementary Table 1.

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