A zinc ion coordinates the folding of a linear polymer programmed to form a knot.
The topology of a molecule has a profound influence on its properties, so a range of sophisticated enzymes has evolved to manipulate molecular entanglements such as knots and chain links. Controlling the topology of synthetic oligomers remains a major challenge, and here we exploit the weak non-covalent interactions in such a molecule to tie a knot around a zinc ion. The folding of the knot is programmed into the covalent structure of the linear molecule, opening new routes for synthesizing macromolecular structures of unprecedented architecture and with well-defined topological properties.
The tools of molecular biology have been used to construct a range of closed knots from DNA and RNA1,2, and optical tweezers have been applied to tie single DNA or protein molecules manually into open knots3. Synthetic strategies for the preparation of small-molecule knots have relied on the templating effects of non-covalent interactions to direct covalent-bond formation4,5,6,7. Attempts to exploit the ligand geometry around an octahedral metal centre to create a molecular trefoil knot8 in conventional template synthesis have not been successful. We tested an alternative approach in which a metal ion is added to a presynthesized oligomer equipped with appropriate recognition sites that should cause spontaneous folding into an open knot9.
We used molecular modelling to design two appropriate building blocks (Fig. 1a), a bidentate ligand (1) and a complementary rigid linker (2), which we covalently connected to give the linear oligomer 3. Addition of one equivalent of zinc perchlorate, Zn(ClO4)2, to a solution of oligomer 3 in deuterodichloromethane caused spontaneous and quantitative conversion to a new species, which was accompanied by marked changes in the proton nuclear magnetic resonance (NMR) spectrum (Fig. 1b). Large shifts were evident in the aromatic signals and the methylene protons became non-equivalent, which suggests that the flexible chains are locked in a single conformation in the complex.
Fast-atom-bombardment mass spectrometry confirmed that a 1:1 complex had been formed and that no higher-order species were present. An X-ray crystal structure of the Zn3(PF6)2 complex (CCDC access no. 163073) proved that the open-knot architecture had been formed in solution. The non-covalent interactions that control folding are apparent in the structure shown in Fig. 1c: metal-ion coordination organizes the core of the knot, and the linker bipyridine subunits (2) straddle the ligands (1) as a result of aromatic interactions that organize the outside of the knot10.
The folding process is fully reversible. Addition of zinc ions to oligomer 3 quantitatively folds the knot, addition of chloride quantitatively unfolds it to yield the free oligomer, and addition of silver ions (which precipitate the chloride) refolds it. The system can be repeatedly cycled through this process. The open-knot Zn32+ represents an important new synthetic intermediate for the assembly of a range of topologically complex molecular architectures. It can be readily prepared on a gram scale, and the terminal hydroxyl groups provide sites for elaboration. Macrocyclization would yield a closed trefoil knot, bulky stopper groups could mechanically trap an open knot, and polymerization would create entangled knotted polymers11.
References
Seeman, N. C. Angew. Chem. Int. Ed. 37, 3220–3228 (1998).
Wang, H., Di Gate, R. & Seeman, N. C. Proc. Natl Acad. Sci. USA 93, 9477–9482 (1996).
Arai, Y. et al. Nature 399, 446–448 (1999).
Dietrich-Buchecker, C. & Sauvage, J.-P Angew. Chem. Int. Ed. 28, 189–192 (1989).
Dietrich-Buchecker, C., Rapenne, G. & Sauvage, J.-P in Molecular Catenanes, Rotaxanes and Knots: A Journey Through the World of Molecular Topology (eds Sauvage, J.-P & Dietrich-Buchecker, C.) 107–142 (Wiley-VCH, Weinheim, 1999).
Ashton, P. R. et al. Liebigs Ann. Recueil 1997, 2485–2494 (1997).
Safarowsky, O., Nieger, M., Fröhlich, R. & Vögtle, F. Angew. Chem. Int. Ed. 39, 1616–1618 (2000).
Sokolov, V. I. Russ. Chem. Rev. 42, 452–463 (1973).
Carina, R. F., Dietrich-Buchecker, C. & Sauvage, J.-P J. Am. Chem. Soc. 118, 9110–9116 (1996).
Breault, G. A., Hunter, C. A. & Mayers, P. C. J. Am. Chem. Soc. 120, 3402–3410 (1998).
Breault, G. A., Hunter, C. A. & Mayers, P. C. Tetrahedron 55, 5265–5293 (1999).
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Adams, H., Ashworth, E., Breault, G. et al. Knot tied around an octahedral metal centre. Nature 411, 763 (2001). https://doi.org/10.1038/35081143
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DOI: https://doi.org/10.1038/35081143
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