The self-assembly of multiple copies of a simple subunit can be used to form larger, more complex structures—for example, viral capsids in Nature or similar synthetic, capsule-like structures whose cavities can be loaded with useful cargoes. Controlling the self-assembly of large synthetic “nanocapsules” in a rational manner can be challenging. Pentagon-shaped substructures, for example, can be used in the construction of cages with fivefold symmetry axes, such as in some icosahedral viral capsids. However, synthetic cages made from building blocks with fivefold symmetry are rare.
Jonathan R. Nitschke, University of Cambridge, UK, and colleagues have prepared nanocages of different sizes (example pictured) derived from pentatopic pyrrole-based subunits. The team prepared a pentakis(biphenyleneamine) pyrrole derivative using Suzuki–Miyaura cross-couplings. This penta-amine can react with formylpyridines to give ligands with fivefold symmetry and bidentate groups at the ends of all five “arms”. These ligands can be combined with metal ions to form cages. For example, the addition of Co(NTf2)2 led to the formation of a dodecahedral cage with 20 cobalt centers, 12 ligands, and an overall diameter of ca. 5 nm.
The team then tuned the coordination number of the metal ions and the denticity and size of the ligands to create progressively larger cages. They used a formyl-substituted bipyridine instead of a formylpyridine to create tridentate groups as well as zinc instead of copper to obtain a cage with 30 Zn centers and 12 ligands with an overall diameter of ca. 6 nm. When the researchers added another phenylene group into each “arm” of the ligand, they obtained an even larger Zn-based cage, which has an enclosed volume of over 92 nm3. Larger cavities could allow nanocages to carry large biomolecules as cargo.
- Systematic construction of progressively larger capsules from a fivefold linking pyrrole-based subcomponent,
Kai Wu, Tanya K. Ronson, Pingru Su, Zhi Chen, Leonard Goh, Andrew W. Heard, Xiaopeng Li, Fabian Klautzsch, Christoph A. Schalley, Mladen Vinković, Jonathan R. Nitschke,
Nat. Synth. 2023.