Abstract
Secondary electrostatic interactions between adjacent hydrogen bonds can have a significant effect on the stability of a supramolecular complex. In theory, the binding strength should be maximized if all the hydrogen-bond donors (D) are on one component and all the hydrogen-bond acceptors (A) are on the other. Here, we describe a readily accessible AAAA–DDDD quadruple hydrogen-bonding array that exhibits exceptionally strong binding for a small-molecule hydrogen-bonded complex in a range of different solvents (Ka > 3 × 1012 M–1 in CH2Cl2, 1.5 × 106 M–1 in CH3CN and 3.4 × 105 M–1 in 10% v/v DMSO/CHCl3). The association constant in CH2Cl2 corresponds to a binding free energy (ΔG) in excess of –71 kJ mol–1 (more than 20% of the thermodynamic stability of a carbon–carbon covalent bond), which is remarkable for a supramolecular complex held together by just four intercomponent hydrogen bonds.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
de Greef, T. F. A. et al. Supramolecular polymerization. Chem. Rev. 109, 5697–5754 (2009).
Fathalla, M., Lawrence, C. M., Zhang, N., Sessler, J. L. & Jayawickramarajah, J. Base-pairing mediated non-covalent polymers. Chem. Soc. Rev. 38, 1608–1620 (2009).
de Greef, T. F. A. & Meijer, E. W. Supramolecular polymers. Nature 453, 171–173 (2008).
Wilson, A. J. Non-covalent polymer assembly using arrays of hydrogen-bonds. Soft Matter 3, 409–425 (2007).
Zimmerman, S. C. & Corbin, P. S. Heteroaromatic modules for self-assembly using multiple hydrogen bonds. Struct. Bonding (Berlin) 96, 63–94 (2000).
Jorgensen, W. L. & Pranata, J. Importance of secondary interactions in triply hydrogen bonded complexes: guanine–cytosine vs uracil-2,6-diaminopyridine. J. Am. Chem. Soc. 112, 2008–2010 (1990).
Popelier, P. L. A. & Joubert, L. The elusive atomic rationale for DNA base pair stability. J. Am. Chem. Soc. 124, 8725–8729 (2002).
Quinn, J. R., Zimmerman, S. C., Del Bene, J. E. & Shavitt, I. Does the A·T or G·C base-pair possess enhanced stability? Quantifying the effects of CH···O interactions and secondary interactions on base-pair stability using phenomenological analysis and ab initio calculations. J. Am. Chem. Soc. 129, 934–941 (2007).
Kyogoku, Y., Lord, R. C. & Rich, A. The effect of substituents on the hydrogen bonding of adenine and uracil derivatives. Proc. Natl Acad. Sci. USA 57, 250–257 (1967).
Kyogoku, Y., Lord, R. C. & Rich, A. An infrared study of the hydrogen-bonding specificity of hypoxanthine and other nucleic acid derivatives. Biochim. Biophys. Acta 179, 10–17 (1969).
Murray, T. J. & Zimmerman, S. C. New triply hydrogen bonded complexes with highly variable stabilities. J. Am. Chem. Soc. 114, 4010–4011 (1992).
Bell, D. A. & Anslyn, E. V. Establishing a cationic AAA–DDD hydrogen bonding complex. Tetrahedron 51, 7161–7172 (1995).
Djurdjevic, S. et al. Extremely strong and readily accessible AAA–DDD triple hydrogen bond complexes. J. Am. Chem. Soc. 129, 476–477 (2007).
Blight, B. A. et al. AAA–DDD-triple hydrogen bond complexes. J. Am. Chem. Soc. 131, 14116–14122 (2009).
Sartorius, J. & Schneider, H.-J. A general scheme based on empirical increments for the prediction of hydrogen-bond associations of nucleobases and of synthetic host–guest complexes. Chem. Eur. J. 2, 1446–1452 (1996).
Beijer, F. H., Kooijman, H., Spek, A. L., Sijbesma, R. P. & Meijer, E. W. Self-complementarity achieved through quadruple hydrogen bonding. Angew. Chem. Int. Ed. 37, 75–78 (1998).
Sijbesma, R. P. et al. Reversible polymers formed from self-complementary monomers using quadruple hydrogen bonding. Science 278, 1601–1604 (1997).
Ligthart, G. B. W. L., Ohkawa, H., Sijbesma, R. P. & Meijer, E. W. Complementary quadruple hydrogen bonding in supramolecular copolymers. J. Am. Chem. Soc. 127, 810–811 (2005).
Lafitte, V. G. H. et al. Quadruply hydrogen bonded cytosine modules for supramolecular applications. J. Am. Chem. Soc. 128, 6544–6545 (2006).
Beijer, F. H., Sijbesma, R. P., Kooijman, H., Spek, A. L. & Meijer, E. W. Strong dimerization of ureidopyrimidones via hydrogen bonding. J. Am. Chem. Soc. 120, 6761–6769 (1998).
Greco, E. et al. Cytosine modules in quadruple hydrogen bonded arrays. New J. Chem. 34, 2634–2642 (1998).
Corbin, P. S. & Zimmerman, S. C. Self-association without regard to prototropy. A heterocycle that forms extremely stable quadruply hydrogen-bonded dimers. J. Am. Chem. Soc. 120, 9710–9711 (1998).
Park, T., Zimmerman, S. C. & Nakashima, S. A highly stable quadruply hydrogen-bonded heterocomplex useful for supramolecular polymer blends. J. Am. Chem. Soc. 127, 6520–6521 (2005).
Kuykendall, D. W., Anderson, C. A. & Zimmerman, S. C. Hydrogen-bonded DeUG·DAN heterocomplex: structure and stability and a scalable synthesis of DeUG with reactive functionality. Org. Lett. 11, 61–64 (2009).
Brammer, S., Lüning, U. & Kühl, C. A new quadruply bound heterodimer DDAD·AADA and investigations into the association process. Eur. J. Org. Chem. 4054–4062 (2002).
Taubitz, J. & Lüning, U. The AAAA·DDDD hydrogen bond dimer. Synthesis of a soluble sulfurane as AAAA domain and generation of a DDDD counterpart. Aust. J. Chem. 62, 1550–1555 (2009).
Hisamatsu, Y., Shirai, N., Ikeda, S.-i. & Odashima, K. A new quadruple hydrogen-bonding module based on five-membered heterocyclic urea structure. Org. Lett. 12, 1776–1779 (2010).
McGhee, A. M., Kilner, C. & Wilson, A. J. Conformer independent heterodimerisation of linear arrays using three hydrogen bonds. Chem. Commun. 344–346 (2008).
Connors, K. A. Binding Constants: The Measurement of Molecular Complex Stability (Wiley-Interscience, 1987).
Hunter, C. A. Quantifying intermolecular interactions: guidelines for the molecular recognition toolbox. Angew. Chem. Int. Ed. 43, 5310–5324 (2004).
Lafitte, V. G. H., Aliev, A. E., Hailes, H. C., Bala, K. & Golding, P. Ureidopyrimidones incorporating a functionalizable p-aminophenyl electron-donating group at C-6. J. Org. Chem. 70, 2701–2707 (2005).
Chapman, K. T. & Still, W. C. A remarkable effect of solvent size on the stability of a molecular complex. J. Am. Chem. Soc. 111, 3075–3077 (1989).
Mecozzi, S. & Rebek, J. Jr. The 55% solution: a formula for molecular recognition in the liquid state. Chem. Eur. J. 4, 1016–1022 (1998).
Acknowledgements
The authors thank S. Cockroft (University of Edinburgh) for useful discussions and performing the electrostatic potential computations. This work was supported by the Engineering and Physical Sciences Research Council (EPSRC). D.A.L. and C.A.H. are EPSRC Senior Research Fellows. B.A.B. is a Marie Curie Fellow (IIF) within the European Union 7th Framework Programme.
Author information
Authors and Affiliations
Contributions
P.I.T.T. carried out the experimental work. P.I.T.T., B.A.B., D.A.L. and H.M. contributed to the design of the experiments and analysis of the data. C.A.H. designed the complex stability models and calculations. All of the authors contributed to writing the paper.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary information
Supplementary information (PDF 3705 kb)
Rights and permissions
About this article
Cite this article
Blight, B., Hunter, C., Leigh, D. et al. An AAAA–DDDD quadruple hydrogen-bond array. Nature Chem 3, 244–248 (2011). https://doi.org/10.1038/nchem.987
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nchem.987
This article is cited by
-
Intrinsic Self-Healing Chemistry for Next-Generation Flexible Energy Storage Devices
Nano-Micro Letters (2023)
-
Quantum chemical study in exploring the role of donor→acceptor interactions in 1,3-bis carbene-stabilized guanidinium cations
Journal of Molecular Modeling (2021)
-
Computational study of the thermodynamic stabilities of hydrogen-bonded complexes in solution
Theoretical Chemistry Accounts (2014)
-
Unique properties of amphiphilic POSS and their applications
Polymer Journal (2013)
-
Attractive arrays
Nature Chemistry (2011)