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

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.

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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

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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)

Supplementary information

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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