70 71 D I A M O N D L I G H T S O U R C E A N N U A L R E V I E W 2 0 1 9 / 2 0 D I A M O N D L I G H T S O U R C E A N N U A L R E V I E W 2 0 1 9 / 2 0 The first nanocagewith antiaromatic walls Related publication: Yamashina M., Tanaka Y., Lavendomme R., Ronson T. K., Pittelkow M. & Nitschke J. R. An antiaromatic-walled nanospace. Nature 574 , 511 (2019). DOI: 10.1038/s41586-019-1661-x Publication keywords: Supramolecular cage; Self-assembly; Antiaromaticity; Host-guest N anocages are complex, functional structures with nanometre-sized cavities. They already have a range of applications in chemistry, medicine and environmental science. Researchers have been working with large molecules with an inner cavity that can host a smaller ‘guest’ molecule. The nature of the host can modify the properties of the guest molecule – for example, neutralising a toxic compound. Although a wide range of molecular hosts have been investigated, until now none were made using ‘antiaromatic’ subunits, which are unusually unstable and difficult to isolate. Researchers working in the Nitschke group at the University of Cambridge synthesised a host species fromantiaromatic compounds in order to study the properties of guests nesting inside the unusual nanospace. Using X-ray crystallography on the Small Molecule Single Crystal Diffraction beamline l19, they were able to determine the structure of the new host. Their work demonstrated the construction of an anti-aromatic-walled nanospace, the first of its kind, within a self-assembled nanocage, and the magnetic effects on guests nesting inside this nanospace. The experimental results agreed with theoretical models. As this study describes the first host of its kind, more work is needed before we fully understand their potential applications. Hollow molecular hosts can encapsulate smaller guests. These guest molecules can exhibit unusual reactivity and properties, in accordance with the properties of the“walls”that form the internal space 1 . Since the first report of a self-assembled nanocage held together using metal-ion coordination and capable of binding diverse guests in 1995 2 , many research groups have reported molecular hosts having different sizes, shapes, and volumes. The nanocages reported so far mostly have walls made up of aromatic molecules (e.g. single benzene rings, and multiple such rings fused together). Nanocages with antiaromatic (a cyclic molecule with 4n π electrons that is highly reactive and unstable) walls should have different properties to those of nanocages with aromatic walls. The magnetic properties of a nanospace with antiaromatic walls were hypothesised to be particularly intriguing, as antiaromaticity is predicted to enhance the local magnetic field inside the nanocage. Such an antiaromatic-walled nanospace has not been reported, and therefore their properties have never been experimentally clarified. To utilise antiaromatic compounds as building blocks for nanocage construction, certain properties are desireable: (i) high stability, (ii) high symmetry, (iii) strong antiaromaticity, (iv) small molecular size but large antiaromatic surface, and (v) facile synthesis and functionalisation. In order to construct an antiaromatic-walled nanospace, Ni II -dimesitylnorcorrole, first reported in 2012 3 , was chosen as an antiaromatic porphyrin-like molecule. This norcorrole is a suitable building block for the construction of an antiaromatic-walled nanospace because it fully satisfies these requirements. A di(aniline)-based subcomponent (Fig.1a) was synthesised from Ni II - dimesitylnorcorrole in three steps.Then the antiaromatic cage was constructed using subcomponent self-assembly 4 . Di(aniline)-based subcomponent (6 equiv.), 2-formylpyridine (12 equiv.) and Fe II bis(trifluoromethanesulfonyl) imide (NTf 2 – ) (4 equiv.) were mixed in CH 3 CN, resulting in the quantitative formation of the Fe 4 L 6 cage as the uniquely observed product (Fig.1a). Characterisation was carried out by nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and single crystal X-ray diffraction analyses. In organic chemistry, NMR and MS techniques are generally powerful tools for investigating chemical structures. However, these analyses are not sufficient for large and complicated compounds such as supramolecular cages since it is quite difficult to see their three-dimensional structural details. Single crystal X-ray diffraction analysis is the only way to determine their structure Crystallography Group Beamline I19 precisely.When using our in-house diffractometer, structural refinement of the supramolecular cage reported in this study was not feasible, owing to the large size of the molecular cage (molecular weight = 8080.88 g/mol) containing large voids with disordered solvent molecules and counteranions. Single crystal X-ray diffraction at the l19 beamline at Diamond Light Source was used to obtain unambiguous evidence for the formation of the supramolecular cage. According to the result from the l19 beamline, six ligands bridge four octahedral Fe II centres to provide a T -symmetric tetrahedral cage having four apertures of ~3.3 A on the faces. All Fe II centres in each tetrahedron have the same Δ (right-handed) or Λ (left-handed) chiral configurations (Fig.1b). The metal–metal distances are 21.9 A for Fe...Fe and 14.6 A between Ni...Ni antipodes. Each norcorrole wall displays a 165.4(3)° bend inwards. As a result of this bending, the face aperture sizes are minimised via stacking between mesityl groups and the neighboring norcorrole edges in the crystal. The cavity volume for the X-ray crystal structure was estimated using the PLATON program to be 1150 A 3 , which is a suitable size for the encapsulation of organic molecules. To investigate the extent of the antiaromaticity experienced within the void volume of cage, nucleus-independent chemical shift (NICS) calculations were carried out based on the X-ray crystal structure. The three-dimensional NICS iso grid of the cage revealed an enhanced antiaromaticity-induced magnetic fieldwithin the cavity (Fig.1b).The calculated NICS values around the centroid within the cage were consistently high, and the value at the centroid of the cage became approximately six times larger than the corresponding point above an unassembled norcorrole panel. This result indicates that the six norcorrole walls have an additive effect on the antiaromaticity experienced within the nanospace. Host–guest studies were conducted to investigate experimentally the effect of guest binding within the antiaromatic-walled cavity of the cage. In the 1 H NMR spectrum, remarkably, the signal of encapsulated coronene was shifted downfield by 8.1 ppm compared to the free guest (Fig.2), as a result of the antiaromatic deshielding effect from the surrounding norcorrole walls. Similarly, six other polyaromatic molecules (e.g., a functionalised fullerene and a carbon nanobelt 5 ) (Fig. 3) were successfully encapsulated within the nanospace, with chemical shift values moved up to 15 ppm downfield from their free values.This shift of 15 ppm from that of the free guest is the largest 1 H NMR chemical shift displacement resulting from an antiaromatic environment observed so far. This cage may thus be considered as a new type of NMR shift reagent, moving guest signals well beyond the usual NMR frequency range and opening the way to further probing the effects of an antiaromatic environment on a nanospace. References: 1. Cook T.R. et al. Metal-organic frameworks and self-assembled supramolecular coordination complexes: comparing and contrasting the design, synthesis, and functionality of metal-organic materials. Chem Rev. 113 , 734-77 (2013). DOI: 10.1021/cr3002824 2. Fujita M. et al. , Self-assembly of ten molecules into nanometre-sized organic host frameworks. Nature 378 , 469–471 (1995). DOI: 10.1038/378469a0 3. Ito, T. et al. , Gram-scale synthesis of nickel(II) norcorrole: the smallest antiaromatic porphyrinoid. Angew. Chem. Int. Ed. 51 , 8542-8545 (2012). DOI: 10.1002/anie.201204395 4. Zhang, D. et al. , Functional capsules via subcomponent self-assembly. Acc. Chem. Res. 51, 2423-2436 (2018). DOI: 10.1021/acs.accounts.8b00303 5. Povie, G. et al. , Synthesis of a carbon nanobelt. Science 356 , 172-175 (2017) DOI: 10.1126/science.aam8158 Funding acknowledgement: European Research Council (695009); UK Engineering and Physical Sciences Research Council (EPSRC, EP/P027067/1); Japan Society for the Promotion of Science (JSPS) for an Overseas Research Fellowship; FondationWiener- Anspach postdoctoral fellowship; Danish Council for Independent Research (DFF 4181-00206). Corresponding author: Prof Jonathan R. Nitschke, University of Cambridge,
[email protected] Figure 2: Host-guest study with antiaromatic nanocage; (a) Encapsulation of coronenes and an MM3-optimised structure of host-guest complex. (b) Partial 1H NMR spectrum of encapsulated coronene, showing a signal for the encapsulated guests in the downfield region. Figure 3: Molecules observed to bind within the nanocage. Figure 1: Chemical structure of an antiaromatic-walled nanospace; (a) construction of antiaromatic-walled nanospace. (b) X-ray crystal structure with a 3D NICS grid, showing magnetic deshielding experienced within the nanospace. Antiaromaticity effects becomes stronger in the order of yellow < orange < red color.