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An AAAA–DDDD quadruple hydrogen-bond array

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.

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Figure 1: Examples of triple hydrogen-bond arrays and their association constants in various solvents.
Figure 2: Examples of quadruple hydrogen-bond arrays and their association constants in various solvents.
Figure 3: Synthetic routes to DDDD+ 12 and AAAA 13.
Figure 4: UV/Vis titration of AAAA 13 with DDDD+ 12 in CH2Cl2.
Figure 5: 1H NMR spectra (500 MHz, CD2Cl2, 298 K) of 12 (top), complex 12·13 (middle) and 13 (bottom).
Figure 6: UV/vis competition experiment in which 13 is displaced from 12·13 by a large excess of 6.
Figure 7: UV/vis titration experiments in which K12·13 and K13·(12·13) are measured by addition of 12 to 13 in CH3CN or 10% DMSO in CHCl3.

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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.

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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.

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Correspondence to David A. Leigh.

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The authors declare no competing financial interests.

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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

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