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Sequence-selective assembly of tweezer molecules on linear templates enables frameshift-reading of sequence information

Nature Chemistry volume 2, pages 653–660 (2010)Cite this article

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Abstract

Information storage and processing is carried out at the level of individual macromolecules in biological systems, but there is no reason, in principle, why synthetic copolymers should not be used for the same purpose. Previous work has suggested that monomer sequence information in chain-folding synthetic copolyimides can be recognized by tweezer-type molecules binding to adjacent triplet sequences, and we show here that different tweezer molecules can show different sequence selectivities. This work, based on 1H NMR spectroscopy in solution and on single-crystal X-ray analysis of tweezer–oligomer complexes in the solid state, provides the first clear-cut demonstration of polyimide chain-folding and adjacent-tweezer binding. It also reveals a new and entirely unexpected mechanism for sequence recognition, which, by analogy with a related process in biomolecular information processing, may be termed ‘frameshift-reading’. The ability of one particular tweezer molecule to detect, with exceptionally high sensitivity, long-range sequence information in chain-folding aromatic copolyimides is readily explained by this novel process.

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Figure 1: Proposed19,20,21 chain folding of a polyimide-sulfone and multiple tweezer binding at adjacent triplet sequences.
Figure 2: X-ray structure (two perpendicular views) of a 2:1 complex [82+1] between ferrocenyl tweezer molecule 8 and bis-pyromellitimide oligomer 1.
Figure 3: Job plots for complexation of 8 (dashed line) and 9 (solid line) with bis(diimide) oligomer 2, based on 1H NMR complexation shifts of the aromatic diimide resonances in chloroform/hexafluoropropan-2-ol (6:1 v/v).
Figure 4: Minimized computational models (molecular mechanics with charge equilibration) of the 1:1 complex between tweezer molecule 9 and the bis-pyromellitimide oligomer 1 (a), and the 2:1 complex between tweezer molecule 9 and the tris-diimide oligomer 3 (b).
Figure 5: 1H NMR spectra showing complexation shifts of different resonances for tris-diimide oligomer 3 (lower trace) in the presence of tweezer molecule 9, at 1:1 (centre trace) and 1:2 (upper trace) molar ratios, respectively.
Figure 6: X-ray structure of the complex between macrocycle 11 and tweezer molecule 9, showing molecular stacking along the crystallographic a-direction.
Figure 7: Chain folding and multiple binding to different polyimide triplet sequences by different tweezer molecules.

References

  1. Watson, J. D. & Crick, F. H. C. A structure for deoxyribose nucleic acid. Nature 171, 737–738 (1953).

    Article  CAS  Google Scholar 

  2. Wilkins, M. H. F., Stokes, A. R. & Wilson, H. R. Molecular structure of deoxypentose nucleic acids. Nature 171, 738–740 (1953).

    Article  CAS  Google Scholar 

  3. Franklin R. E. & Gosling, R. G. Molecular configuration in sodium thymonucleate. Nature 171, 740–741 (1953).

    Article  CAS  Google Scholar 

  4. Crick, F. H. C. On protein synthesis. Symp. Soc. Exptl Biol. 12, 138–163 (1958).

    CAS  Google Scholar 

  5. Nirenberg, M. Historical review: deciphering the genetic code—a personal account. Trends Biochem. Sci. 29, 46–54 (2004).

    Article  CAS  Google Scholar 

  6. Dawkins, C. R. The Blind Watchmaker (Longmans, 1986).

  7. Lodish, H. et al. Molecular Cell Biology 6th edn (Freeman, 2007).

  8. Burd, C. & Weck, M. Self-sorting in polymers. Macromolecules 38, 7225–7230 (2005).

    Article  CAS  Google Scholar 

  9. Weck, M. Side-chain functionalized supramolecular polymers. Polym. Int. 56, 453–460 (2007).

    Article  CAS  Google Scholar 

  10. Harmata, M. Chiral molecular tweezers. Acc. Chem. Res. 37, 862–873 (2004).

    Article  CAS  Google Scholar 

  11. Klärner, F.-G. & Kahlert, B. Molecular tweezers and clips as synthetic receptors. Molecular recognition and dynamics in receptor−substrate complexes. Acc. Chem. Res. 36, 919–932 (2003).

    Article  Google Scholar 

  12. Chen, C. W. & Whitlock, H. W. Molecular tweezers—a simple model of bifunctional intercalation. J. Am. Chem. Soc. 100, 4921–4922 (1978).

    Article  CAS  Google Scholar 

  13. Zimmerman, S. C. & VanZyl, C. M. Rigid molecular tweezers—synthesis, characterization and complexation chemistry of a diacridine. J. Am. Chem. Soc. 109, 7894–7896 (1987).

    Article  CAS  Google Scholar 

  14. Kurebayashi, H., Haino, T., Usui, S. & Fukazawa, Y. Structure of supramolecular complex of flexible molecular tweezers and planar guest in solution. Tetrahedron 57, 8667–8674 (2001).

    Article  CAS  Google Scholar 

  15. Balzani, V. et al. Host−guest complexes between an aromatic molecular tweezer and symmetric and unsymmetric dendrimers with a 4,4′-bipyridinium core. J. Am. Chem. Soc. 128, 637–648 (2006).

    Article  CAS  Google Scholar 

  16. Klärner, F.-G. et al. Molecular tweezer and clip in aqueous solution: unexpected self-assembly, powerful host−guest complex formation, quantum chemical H-1 NMR shift calculation. J. Am. Chem. Soc. 128, 4831–4841 (2006).

    Article  Google Scholar 

  17. Goshe, A. J., Steele, I. M., Ceccarelli, C., Rheingold, A. L. & Bosnich, B. Supramolecular recognition: on the kinetic lability of thermodynamically stable host−guest association complexes. Proc. Natl Acad. Sci. USA 99, 4823–4829 (2002).

    Article  CAS  Google Scholar 

  18. Peng, X.-X., Lu, H.-Y., Han, T. & Chen, C.-F. Synthesis of a novel triptycene-based molecular tweezer and its complexation with paraquat derivatives. Org. Lett. 9, 895–898 (2007).

    Article  CAS  Google Scholar 

  19. Colquhoun, H. M. & Zhu, Z. Recognition of polyimide sequence information by a molecular tweezer. Angew. Chem. Int. Ed. 43, 5040–5045 (2004).

    Article  CAS  Google Scholar 

  20. Colquhoun, H. M., Zhu, Z., Cardin, C. J. & Gan, Y. Principles of sequence-recognition in aromatic polyimides. Chem. Commun. 2650–2652 (2004).

  21. Colquhoun, H. M., Zhu, Z., Cardin, C. J., Gan Y. & Drew, M. G. B. Sterically controlled recognition of macromolecular sequence information by molecular tweezers. J. Am. Chem. Soc. 129, 16163–16174 (2007).

    Article  CAS  Google Scholar 

  22. Colquhoun, H. M., Zhu, Z., Cardin, C. J., Drew, M. G. B. & Gan, Y. Recognition of sequence-information in synthetic copolymer chains by a conformationally-constrained tweezer molecule. Faraday Discuss. 143, 205–220 (2009).

    Article  CAS  Google Scholar 

  23. Hamilton, D. G., Sanders, J. K. M., Davies, J. E., Clegg, W. & Teat, S. J. Neutral [2]catenanes from oxidative coupling of π-stacked components. Chem. Commun. 897–898 (1997).

  24. Hamilton, D. G., Lynch, D. E., Byriel, K. A., Kennard C. H. L. & Sanders, J. K. M. N-alkylation of pyromellitic diimide: solid-state structure of the 1:1 N,N′-diethylpyromellitic diimide 2,6-dimethoxynaphthalene cocrystal. Aust. J. Chem. 51, 441–444 (1998).

    Article  CAS  Google Scholar 

  25. Hamilton, D. G., Davies, J. E., Prodi, L. & Sanders, J. K. M. Synthesis, structure and photophysics of neutral π-associated [2]catenanes. Chem. Eur. J. 4, 608–620 (1998).

    Article  CAS  Google Scholar 

  26. Hamilton, D. G., Feeder, N., Teat, S. J. & Sanders, J. K. M. Reversible synthesis of π-associated [2]catenanes by ring-closing metathesis: towards dynamic combinatorial libraries of catenanes. New J. Chem. 22, 1019–1021 (1998).

    Article  CAS  Google Scholar 

  27. Kaiser, G. et al. Lithium-templated synthesis of a donor−acceptor pseudorotaxane and catenane. Angew. Chem. Int. Ed. 43, 1959–1962 (2004).

    Article  CAS  Google Scholar 

  28. Vignon, S. A. et al. Switchable neutral bistable rotaxanes. J. Am. Chem. Soc. 126, 9884–9885 (2004).

    Article  CAS  Google Scholar 

  29. Iijima, T. et al. Controllable donor−acceptor neutral [2]rotaxanes. Chem. Eur. J. 10, 6375–6392 (2004).

    Article  CAS  Google Scholar 

  30. Pascu, S. I. et al. Cation-reinforced donor−acceptor pseudorotaxanes. New J. Chem. 80–89 (2005).

    Article  CAS  Google Scholar 

  31. Hansen, J. G., Bang, K. S., Thorup N. & Becher, J. Donor−acceptor macrocycles incorporating tetrathiafulvalene and pyromellitic diimide: syntheses and crystal structures. Eur. J. Org. Chem. 2135–2144 (2000).

  32. Colquhoun, H. M., Stoddart, J. F., Williams, D. J., Wolstenholme, J. B. & Zarzycki, R. Second-sphere coordination of cationic platinum complexes by crown ethers—the X-ray crystal-structure of [Pt(bpy)(NH3)2.dibenzo[30]crown-10]2+[PF6]−2.xH2O (x=0.6). Angew. Chem. Int. Ed. Engl. 20, 1051–1053 (1981).

    Article  Google Scholar 

  33. Colquhoun, H. M. et al. Complex-formation between dibenzo-3n-crown-n ethers and the diquat dication. J. Chem. Soc., Chem. Commun. (pre-1996) 1140–1142 (1983).

  34. Allwood, B. L., Spencer, N., Shahriari-Zavareh, H., Stoddart, J. F. & Williams, D. J. Complexation of diquat by a bisparaphenylene-34-crown-10 derivative. J. Chem. Soc., Chem. Commun. (pre-1996) 1061–1064 (1987).

  35. Ashton, P. R., Slawin, A. M. Z., Spencer, N., Stoddart, J. F. & Williams, D. J. Complex formation between bisparaphenylene-(3n+4)-crown-n ethers and the paraquat and diquat dications. J. Chem. Soc., Chem. Commun. (pre-1996) 1066–1069 (1987).

  36. Krebs, F. C. & Jørgensen, M. A new versatile receptor platform. J. Org. Chem. 66, 6169–6173 (2001).

    Article  CAS  Google Scholar 

  37. Koshkakaryan, G. et al. Alternative donor−acceptor stacks from crown ethers and naphthalene diimide derivatives: rapid, selective formation from solution and solid state grinding. J. Am. Chem. Soc. 131, 2078–2079 (2009).

    Article  CAS  Google Scholar 

  38. Peinador, C., Blanco V. & Quintela, J. A new doubly interlocked [2]catenane. J. Am. Chem. Soc. 131, 920–921 (2009).

    Article  CAS  Google Scholar 

  39. Ulrich, S. & Lehn, J.-M. Adaptation and optical signal generation in a constitutional dynamic network. Chem. Eur. J. 15, 5640–5645 (2009).

    Article  CAS  Google Scholar 

  40. Lohr, A., Grüne, M. & Würthner, F. Self-assembly of bis(merocyanine) tweezers into discrete bimolecular π-stacks. Chem. Eur. J. 15, 3691–3705 (2009).

    Article  CAS  Google Scholar 

  41. Harris, F. W. in Polyimides (eds Wilson, D., Stenzenberger, H. D. & Hergenrother, P. M.) Ch. 1 (Chapman and Hall, 1990).

  42. Klod, S. & Kleinpeter, E. Ab initio calculation of the anisotropy effect of multiple bonds and the ring current effect of arenes—application in conformational and configurational analysis. Perkin Trans. 1893–1898 (2001).

  43. Colquhoun, H. M., Zhu, Z. & Williams, D. J. Extreme complementarity in a macrocycle−tweezer complex. Org. Lett. 5, 4353–4356 (2003).

    Article  CAS  Google Scholar 

  44. Nielsen, M. B., et al. Binding studies between tetrathiafulvalene derivatives and cyclobis(paraquat-p-phenylene). J. Org. Chem. 66, 3559–3563 (2001).

    Article  CAS  Google Scholar 

  45. Johnson, Z. I. & Chisholm, S. W. Properties of overlapping genes are conserved across microbial genomes. Genome Res. 14, 2268–2272 (2004).

    Article  CAS  Google Scholar 

  46. Colquhoun, H. M., Williams, D. J. & Zhu, Z. Macrocyclic aromatic ether-imide-sulfones: versatile supramolecular receptors with extreme thermochemical and oxidative stability. J. Am. Chem. Soc. 124, 13346–13347 (2002).

    Article  CAS  Google Scholar 

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Acknowledgements

This research was supported by EPSRC (grant nos EP/C533526/1, EP/E00413X/1, EP/F013663/1 and EP/G026203/1) and by the Royal Society (a Senior Research Fellowship to H.M.C).

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Authors and Affiliations

  1. Department of Chemistry, University of Reading, Whiteknights, RG6 6AD, Reading, UK

    Zhixue Zhu, Christine J. Cardin, Yu Gan & Howard M. Colquhoun

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  1. Zhixue Zhu
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  2. Christine J. Cardin
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  4. Howard M. Colquhoun
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Contributions

Z.Z. and H.M.C. designed the synthetic and spectroscopic experiments and interpreted the resulting data. Z.Z. carried out the experiments and co-wrote the paper. C.J.C. and Y.G. undertook the crystallographic work, including structure solution, refinement and data analysis. H.M.C. conceived and supervised the project, generated the graphics and wrote the paper.

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Correspondence to Howard M. Colquhoun.

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Supplementary information

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Supplementary information (PDF 821 kb)

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Crystallographic data for the complex [82+1] (CIF 34 kb)

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Crystallographic data for the complex [9+11] (CIF 37 kb)

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Zhu, Z., Cardin, C., Gan, Y. et al. Sequence-selective assembly of tweezer molecules on linear templates enables frameshift-reading of sequence information. Nature Chem 2, 653–660 (2010). https://doi.org/10.1038/nchem.699

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