An isolable catenane consisting of two Möbius conjugated nanohoops

Besides its mathematical importance, the Möbius topology (twisted, single-sided strip) is intriguing at the molecular level, as it features structural elegance and distinct properties; however, it carries synthetic challenges. Although some Möbius-type molecules have been isolated by synthetic chemists accompanied by extensive computational studies, the design, preparation, and characterization of stable Möbius-conjugated molecules remain a nontrivial task to date, let alone that of molecular Möbius strips assembling into more complex topologies. Here we report the efficient synthesis, crystal structure, and theoretical study of a catenane consisting of two fully conjugated nanohoops exhibiting Möbius topology in the solid state. This work highlights that oligoparaphenylene-derived nanohoops, a family of highly warped and synthetically challenging conjugated macrocycles, can not only serve as building blocks for interlocked supermolecular structures, but also represent a new class of compounds with isolable Möbius conformations stabilized by non-covalent interactions.

M olecular architectures with fascinating structures have attracted considerable interest across the scientific community for decades. The never-ending pursuits for exploring the frontiers of chemical synthesis have turned many such molecules, from once imaginary pictures or theoretical models, into tangible substances 1,2 . In particular, conjugated molecules displaying Möbius topology are intriguing targets because of their stunning structures and unique aromaticity [3][4][5][6] .
In complement to the conventional Hückel's rule for determining aromaticity, Heilbronner 7 proposed in 1964 that cyclic-conjugated molecules displaying Möbius conformation are aromatic when their cyclic π systems contain 4n delocalized electrons (n is a positive integer, Fig. 1a). This pioneering prediction was validated in 2003 with the first synthetic Möbius aromatic compound (Fig. 1b) 8 . Recently, significant progress in synthesizing Möbius-type molecules has been achieved with the isolation of a number of expanded porphyrin derivatives 9 . The aforementioned compounds showcase creative structural designs relying on well-balanced tuning of molecular strain and rotational flexibility to secure Möbius conformations.

Results
Synthesis and characterization. The synthesis of 1 commenced with phenanthroline-derived arylboronic ester 2 and aryl bromide 3 (Fig. 2), both of which could be readily prepared from simple starting materials. Suzuki-Miyaura cross-coupling between 2 and excess 3 proceeded smoothly to afford product 4, which was further converted to an extended bis(arylboronic ester) 5 through Miyaura borylation. With the precursor for catenane synthesis in hand, we next mixed 5 and a copper hexafluorophosphate salt with a 2:1 molar ratio. Upon the formation of copper(I) complex 6, addition of a palladium catalyst and a fluoride base under the exposure of air initiated Jasti's oxidative homocoupling macrocyclization 21 , generating copper-containing interlocked molecule 7. Without further purification, crude compound 7 was subjected to the demetalation step in the presence of in situ released cyanide. The resulting metal-free catenane 8 was carefully reduced using sodium naphthalenide under cryogenic conditions 22 , producing the target catenane 1. The interlocked structures of 1 and its precursor 8 were characterized by nuclear magnetic resonance (NMR) and mass spectrometry analyses ( Supplementary Fig. 6, [9][10][11]. The observed symmetrical 1 H NMR spectra indicate fast conformational changes within the catenane structures in solution. Additionally, 1 exhibits much better solubility in common organic solvents compared to the monomeric nanohoop 9, likely due to the reduced intermolecular π-π stacking in the solid state. We obtained single crystals by slow diffusion of hexanes into a chloroform solution of 1, and unambiguously confirmed its solidstate structure by X-ray crystallography (Fig. 1c). In addition to the validation of the mechanically linked feature, it was intriguing to observe that both conjugated nanohoops within 1 exclusively adopt Möbius topology in the solid state. Each monomeric nanohoop deviates from C 2 symmetry, likely resulting from noncovalent interaction between the monomers. The average distance between a nitrogen atom and the furthest ipso-carbon within a Herges and co-workers prepared a polyene-derived compound that has been regarded as the first isolated Möbius aromatic macrocycle. c Catenane 1 consisting of Möbius-conjugated nanohoops, with its X-ray crystal structure shown with 30%-probability ellipsoids. Hydrogen atoms and solvent molecules are omitted for clarity monomeric nanohoop is 1.4 nm, and the width of one macrocycle monomer is measured as 1.1 nm. While the phenanthroline moieties remain almost flat, the oligoparaphenylene subunits are unevenly twisted, with torsional angles between neighboring aryl rings ranging from 2.6°to 55.6°(29.4°on average, Supplementary  Fig. 12). With regard to the solid-state packing, the two monomeric nanohoops within a single molecule of 1 display a dihedral angle of 56°, and 1 adopts two opposite orientations that alternatively and parallelly organized in the crystal structure ( Supplementary Fig. 13).
Computational studies. We performed computational studies on the structures optimized from the crystal structure of 1. To probe the magnitude of intramolecular interaction within the catenane structure, the sign(λ 2 )ρ function was employed to examine the real-space non-covalent interaction (NCI) between the two monomeric nanohoops (Fig. 3) 23 . The low-gradient, low-density isosurfaces located at the centers of benzene rings are signs of typical non-bonded interaction commonly observed in small rings. The bent sheets exhibit a mix of green and orange areas, indicating the coexistence of van der Waals interaction and steric repulsion between the monomers. Such an overlap in bent sheets resembles to the isosurface in the benzene dimer 23 as well as biphenyl dimer (Supplementary Fig. 14), where π-π stacking leads to a portion of strong non-bonded interaction. On the basis of energy decomposition analysis (EDA), the overall interaction energy between the monomers results in -84.0 kcal mol −1 in favor of stabilizing the catenane structure (Supplementary Table 3) 24 .
As the anisotropy of the induced current density (ACID) can simulate the density and direction of the induced ring current in a molecular system under an external magnetic field 25,26 , we computed the ACID plot for monomer 9 to examine its aromaticity (Fig. 4a). Clockwise currents can be observed in each individual benzene ring as well as the phenanthroline subunit, indicating local aromaticity in these moieties. Along the bridging C-C bonds, the current densities are comparable to those in the benzene rings.  ARTICLE Specifically, we examined the critical isosurface value (CIV), an indicator of conjugation/delocalization 25 . The results show that the degree of conjugation between adjacent rings is comparable to that in benzene moieties (Supplementary Fig. 15).
To further investigate the electron delocalization over the monomer nanohoop 9 and catenane 1, we carried out electron localization function (ELF) analysis which is also a robust tool for the evaluation of aromaticity 27,28 . The σand π-electron contributions to the ELF are separated for the monomer 9 (Fig. 4b). The ELF π domains display the delocalization of π electrons in all benzene and phenanthroline moieties. Note that the ELF π bifurcation values for the bridging C-C bonds are less than 0.3. According to a previous study on a series of polybenzenoid hydrocarbons, an ELF π bifurcation value smaller than 0.65 should not be attributed to C-C delocalized π bonds 27 . However, the ELF σ bifurcation values range from 0.573 to 0.679 for the bridging C-C bonds ( Supplementary Fig. 16), which are close to the value (0.692) in benzene computed at the same level of theory. Therefore, the delocalization of the bridging C-C bonds is mainly attributed to the σ electrons, similar to the previous arguement by Shaik, Hiberty, and co-workers that the σ-framework of benzene leads to the observed D 6h symmetric structure 29 . The overall ELF total domains in catenane 1 (Fig. 4c) suggest that the electron delocalization along the bridging C-C bonds are comparable to that over the aromatic moieties ( Supplementary Fig. 17). Thus the monomer 9 and catenane 1 could be considered aromatic because each individual ring is aromatic and the bridging C-C bonds are significantly delocalized.

Discussion
In summary, we report an efficient, precise synthesis of catenane 1 consisting of two mechanically linked, fully conjugated nanohoops.  Its crystal structure exhibits unusual topology, representing a rare case of stabilized Möbius twisted π-system in the solid state. Theoretical calculations reveal the aromaticity in the monomer nanohoop as well as a strong driving force for the stabilization of catenane 1 through non-covalent π-π interaction. This work illustrates a productive combination of rational design, synthetic execution, crystallographic analysis, and computational investigation, which would ultimately inspire us and others along the march of discovering challenging and complex molecular architectures.
Data availability. All the data supporting the findings of this study are available within the article and its Supplementary Information files or from the authors on reasonable request. Supplementary crystallographic information files, which include structure factors, have been deposited with the Cambridge Crystallographic Data Centre (CCDC) as deposition number CCDC: 1835146, for compound 1. The data files can be obtained free of charge from http://www.ccdc.cam.ac.uk/data_request/cif.