Biological encapsulants, such as viral capsids and ferritin protein cages, use many identical subunits to tile the surface of a polyhedron. Inspired by these natural systems, synthetic chemists have prepared artificial nanocages with well-defined shapes and cavities. Rational control over the self-assembly of discrete, nanometre-scale, hollow coordination cages composed of simple components remains challenging as a result of the entropic costs associated with binding many subunits together, difficulties in the error-correction processes associated with assembly and increasing surface energy as their size grows. Here we demonstrate the construction of nanocages of increasing size derived from a single pentatopic pyrrole-based subcomponent. Reasoned shifts in the preferred coordination number of the metal ions used, along with the denticity and steric hindrance of the ligands, enabled the generation of progressively larger cages. These structural changes of the cages are reminiscent of the differences in the folding of proteins caused by minor variations in their amino acid sequences; understanding how they affect capsule structure and thus cavity size may help to elucidate the construction principles for larger and functional capsules, capable of binding and carrying large biomolecules as cargoes.
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All data needed to evaluate the conclusions given in the paper are present in the main text and Supplementary Information. The crystallographic data for the structure reported in this paper have been deposited at the Cambridge Crystallographic Data Centre under deposition number CCDC 2193949 (Co-2). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.
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This study was supported by the European Research Council (grant no. 695009), the UK Engineering and Physical Sciences Research Council (EPSRC, grant no. EP/P027067/1) and Astex Pharmaceuticals (grant no. RG73357, Sustaining Innovation Postdoctoral Training Program to A.H.). We thank Diamond Light Source for providing time on Beamline I24. The SAXS data collection was performed with the help of C. Pizzey using beamline B21 of the UK Diamond Light Source, a dedicated beamline for SAXS. This work benefited from the use of the SasView application, originally developed under NSF award DMR-0520547. SasView contains code developed with funding from the European Union’s Horizon 2020 research and innovation programme under the SINE2020 project, grant agreement no. 654000. We thank the University of Cambridge Chemistry Department NMR service for performing some NMR experiments. We thank Thermo Fisher Scientific and the mass team of the University of Cambridge Chemistry Department for help with some mass spectrometry measurements. We also thank J. A. Davies, X. Sun, W. Xue, C. Fuertes-Espinosa and H.-K. Liu for helpful discussion and assistance.
The authors declare no competing interests.
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Extended Data Fig. 1 Preparation of penta-amine A from A1.
Reagents and conditions: (i) Pd(PPh3)4, K3PO4, dioxane:H2O = 4:1, 95 °C, 48 h.
Extended Data Fig. 2 Schematic representation of the metal vertex opening angles of tetrahedral, cubic and dodecahedral frameworks.
a, Stick view of metal ion positions in the different cage frameworks. b, Opening angles (φ) of the metal vertex of the corresponding tetrahedra35,36, cube37, or dodecahedron shown above, between the metal centre C3 axis (grey dashed line) and the ligand vector defined by the two nitrogen atoms of the chelate plane, measured from their crystal structures. φ was calculated as the complementary angle of the dihedral angle between the five-membered chelate plane and the plane formed by the three neighbouring metal centres (highlighted). Colour code: CoII pink, FeII purple, C light blue, N blue). The presence of bulky methyl group and the expansion of frameworks are inferred to both increase φ.
Extended Data Fig. 3 Schematic representation of subcomponent self-assembly of Ni-7.
Only one ligand is shown for clarity.
Supplementary Figs. 1–82 and Tables 1–8.
Supplementary Data 1
Crystallographic data for Co-2 (CCDC reference 2193949).
Supplementary Data 2
Cartesian coordinates of truncated tetrahedron Cu-3.
Supplementary Data 3
Cartesian coordinates of truncated rhombohedron Co-4.
Supplementary Data 4
Cartesian coordinates of icosidodecahedron Zn-5.
Supplementary Data 5
Cartesian coordinates of icosidodecahedron Zn-6.
Supplementary Data 6
Cartesian coordinates of sandwich Ni-7.
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Wu, K., Ronson, T.K., Su, P. et al. Systematic construction of progressively larger capsules from a fivefold linking pyrrole-based subcomponent. Nat. Synth (2023). https://doi.org/10.1038/s44160-023-00276-9