Introduction

[n]Cycloparaphenylenes ([n]CPPs, where n is the number of phenylene groups), consisting of 1,4-linked phenylene unit, have attracted much attention due to their unique π-conjugated structures and physical properties1,2,3. Starting with the pioneering works in 2009–20104,5,6, [n]CPPs with various ring sizes and functional groups have been successfully synthesized over the past decade. Accordingly, tuning of physical properties and functionalization applications such as supramolecular hosts by introducing functional groups to the aryl ring have also been studied7,8,9. In particular, the introduction of well-ordered functional groups on all aromatic rings of [n]CPPs can lead to the occurrence of a unique molecular topology and physical properties due to the macrocyclic molecular structure with a periodical array, such as Tanaka′s alkoxy-bridged [n]CPPs (n = 8, 10) with belt or Möbius topologies10, Du′s methoxy-functionalized [8]CPP11, and Itami′s fully-fluorinated [n]CPPs (n = 10, 12, 14, 16) (Fig. 1a)12,13. On the other hand, there are no examples of functionalization of all benzene rings of [n]CPPs with a small ring size, especially smaller than [7]CPP, due to the strong ring strain and the steric hindrance of the substituents that hampers their synthesis, although partially halogenated [5] and [6]CPPs have been synthesized by Yamago et al. (Fig. 1b)14,15.

Fig. 1: Synthesis of [n]cycloparaphenylenes ([n]CPPs) with multiple functional groups.
figure 1

a [n]CPPs (n ≥ 8) with substituents at all aromatic rings10,11,12,13. b Partially substituted [n]CPPs (n ≤ 6) with a small ring size14,15. c [6]Cycloparaphenylene derivatives consisting of hydroquinone ether units with 2,5-dimethoxy groups at all benzene rings, produced from macrocyclic Au complex (Cy = cyclohexyl) (This work)16. The red-colored bonds represent the bonds formed in the reaction.

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Recently, we have developed a new synthetic method for the [n]CPPs (n = 6, 9-15) via a macrocyclic gold complex16,17. A notable feature of this method is that it employs a triangular-shaped macrocyclic gold complex with Au2-diphosphine units located at the three corners that have stabilized their molecular structure through the aurophilic interactions18,19,20,21. We considered that our synthetic method would be suitable for the multi-functionalization of [n]CPPs with small ring size for the following reasons; i) the aurophilic interactions have degrees of freedom in their bond distances and angles, allowing the formation of the macrocyclic structure even when the multi-functionalization leads to crowding around the Au complex, ii) an Au(I) center coordinates only one aryl ligand, providing a more sterically vacant metal center than the biaryl M(II) complexes (M = Ni, Pd, Pt), and there would be less steric repulsion between the aryl ligands even if the substituents are introduced at the ortho-position (Fig. 1c).

Gaeta et al. reported the synthesis of a [8]CPP derivative incorporating one 2,5-dimethoxyphenylene ring and the inclusion ability toward methylpyridinium salts (Ka = 2.2 × 103 M−1, CDCl3, 25 oC)22. Du et al. reported the synthesis of a [8]CPP derivative with several 2,5-dimethoxy groups23, and that the molecule did not show significant inclusion ability toward various electron-deficient guest molecules. The averaged diameter of [6]CPP is 8.07 Å24,25, which is comparable to that of pillar[5]arenes (ca. 9.0 Å)26, and is expected to recognize guest molecules with a size of alkyl chains that have not been achieved for the CPP system.

In this study, we report the synthesis of the [6]cycloparaphenylene derivative with hydroquinone ether units (2,5-dimethoxy groups) incorporated into all benzene rings by employing the Au-templated CPP synthesis method. In addition, we will explore the host-guest chemistry of this compound and its expansion into rotaxane synthesis. To prove an in-plane aromaticity27,28,29,30,31 predicted in the dication species of cyclopayaphenylene, the electrochemical properties of these compounds will be evaluated.

Results and discussion

Synthesis and characterization of [6]CPP-12OMe

The reaction of 2,2′,5,5′-tetramethoxy-1,1′-biphenyl-4,4′-diyl diboronic acid (L1) with [Au2Cl2(dcpm)] (dcpm = bis(dicyclohexylphosphino)methane) in the presence of Cs2CO3 (1.0:1.0:6.0 molar ratio) in toluene/ethanol/water at 50 °C produced the macrocyclic Au complex, [Au2(C6H4−2,5-(OMe)2)2(dcpm)]3 (Au-1), in 84% isolated yield. Then, the oxidative chlorination32 of Au-1 occurs upon the addition of 3 equivalents of PhICl2 in DMF at –60 °C. The reaction mixture after stirring at 25 °C for 5 h was purified by silica gel column chromatography to give [6]CPP-12OMe (1) in 34% yield (Fig. 2a).

Fig. 2: Synthesis and characterization of [6]CPP-12OMe (1).
figure 2

a Synthetic route for 1. Reagents and conditions; (i) Cs2CO3 (6 equiv.), toluene/ethanol/water, 50 °C, 20 h, (ii) PhICl2 (3 equiv.), DMF, –60 °C to 25 °C, 5.5 h (Cy = cyclohexyl). b, c The oak ridge thermal ellipsoid plot (ORTEP) drawings of (b) Au-1 and (c) 1 (30% level of probability for thermal ellipsoids; gray, carbon; red, oxygen; yellow, gold; orange, phosphorus; light green, chlorine). Hydrogen atoms are omitted for clarity.

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The molecular structure of macrocyclic Au complex (Au-1) was confirmed by X-ray crystallography (Fig. 2b). The complex adopted the triangular shaped structure with twisted Au-P-C-P-Au groups at the three corners, similar to that the non-substituted Au complex, [Au2(C6H4)2(dcpm)]3, reported in our previous study (CCDC: 1994843)16. The distance between the two neighboring gold atoms in helical corners (3.508(1), 3.245(1), 3.1199(8) Å) are observed to be as significantly longer than that of [Au2(C6H4)2(dcpm)]3 (3.1799(11), 3.0696(8), 3.0696(8) Å) (Supplementary Fig. 31), which indicates that the triangular structure can be maintained even when the bulky methoxy groups are introduced at the ortho positions of the arylene linkers. This result clearly showed that our Au-templated method has a wide range of substrate applicability.

The single crystals of 1 suitable for X-ray crystallography were obtained via the vapor diffusion of n-hexane into 1,2-dichloroethane solution of the molecule. The crystal structure was analyzed as 1,2-dichloroethane incorporated structure (Fig. 2c). The all-methoxy groups of the dimethoxybenzenes are oriented in the same direction in the molecule, resulting in two enantiomers, pR and pS, with planar chirality depending on the orientation of the methoxy groups. The molecule adopted an elliptical molecular structure similar to [6]CPP with a slightly lengthened diameter (⌀avg = 8.15 Å). Interestingly, the averaged dihedral angle between two phenylene rings (θavg) was estimated to be 24.2°, which is narrower than that of [6]CPP (28.1°)24,25. Rathore reported synthesis, molecular structure, and electrochemical properties of oligo(p-phenylene)s with 2,5-dimethoxy groups, (C6H4−2,5-(OMe)2)nH2 (n = 2-9)33, which are a linear analog of 1. The dihedral angle (56°) in the crystal structure of (C6H4−2,5-(OMe)2)3H2 was significantly wider than that of p-terphenyl ( ≤ 1°)34, which is in contrast to that of the CPP system in this study.

The strain energy of 1, as simulated through the density functional theory (DFT) calculations (ωB97M-V/def2-TZVP//TPSS-D3(BJ)/def2-SVP) based on the homodesmotic reaction using ORCA35 (Supplementary Table 3), was unexpectedly estimated to be lower (88.2 kcal mol–1) compared to that of [6]CPP (92.6 kcal mol–1) calculated at the same level, despite the introduction of bulky methoxy groups. Further computational studies, including bond critical points (BCPs) / quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) analyses using Multiwfn36 and NCIPLOT37 programs, have demonstrated the formation of intramolecular CH…O hydrogen bonds between methoxy oxygens and aryl hydrogens of another benzene ring (Supplementary Figs. 18-19). Thus, the lower strain energy of 1 compared to [6]CPP can be attributed to a contribution from stabilization through the multiple hydrogen bonds. This interaction tends to be weak in a less-strained molecule such as (C6H4−2,5-(OMe)2)3H233 by a large Ar-Ar dihedral angle primarily due to the steric hindrance. Therefore, the formation of the tubular conformation in 1 can be ascribed to the restricted change in dihedral angles due to the strained macrocyclic structure, along with the structure-specific intramolecular CH…O hydrogen bonds.

The above-mentioned molecular conformations in the crystal structures have also been observed in solution. The 1H NMR signal of arylene protons (Ar-H) of 1 appeared as a slightly broad singlet peak at 7.34 ppm (400 MHz, CDCl3, 298 K). The fact that the corresponding signal of (C6H4−2,5-(OMe)2)nH233 was observed in 6.9 ppm suggests that all arylene rings of 1 are oriented perpendicular to the CPP macroring as in the crystal structure, and thus the downfield shift of the Ar-H proton of 1 compared to that of (C6H4−2,5-(OMe)2)nH2 would be attributed to less shielding effects from the other arylene rings due to the small Ar-Ar dihedral angles. The variable-temperature NMR measurements, DFT calculations, and chiral high performance liquid chromatography (HPLC) analysis suggested that the ring flipping of 1 occurred rapidly, and that the two enantiomers are fast exchanging in solution (Supplementary Figs. 14–16).

The cyclic voltammogram of 1 showed the reversible redox wave with E1/2 = 0.004 V vs. Fc/Fc+ (Epa = 0.02 V, Epc = –0.06 V), which is drastically lower potential than that of [6]CPP (Epa = 0.48 V)24,25 (Fig. 3a). To understanding the difference in the electrochemical properties, the frontier orbitals were simulated by DFT calculations35 (Fig. 3b). Interestingly, although the shape of the frontier orbitals was comparable, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) levels of 1 (–4.42, –1.62 eV) were found to be drastically higher than those of [6]CPP (–5.11, –2.18 eV). The significant increase in these levels would be due to i) the effect of the electron-donating nature of the methoxy groups and ii) the increase in ring strain and π-conjugation based on the decrease in Ar-Ar dihedral angle caused by the intramolecular CH…O hydrogen bonds of the methoxy groups38.

Fig. 3: Electrochemical properties of [6]CPP-12OMe (1).
figure 3

a Cyclic voltammograms of 2 (red solid line) and [6]CPP (black dashed line) (CH2Cl2, [M] = 1.0 × 10–3 M, electrolyte: 0.1 M TBAPF6, scan rate: 100 mV s–1, r.t.) (Epa: anodic peak potential, Epc: cathodic peak potential). b Energy diagrams and Kohn-Sham orbitals of 1 (right) and [6]CPP (left) (B3LYP/def2-SVP//TPSS-D3(BJ)/def2-SVP, isosurface; 0.02). Source data are available as a Source data file.

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Chemical Oxidation of [6]CPP-12OMe

The chemical oxidation of [6]CPP-12OMe (1) with [N(C6H4−4-Br)3]SbCl6 (Magic Blue, MB) was monitored by ultraviolet/visible/near-infrared (UV/vis/NIR) spectra (Fig. 4a). In the neutral state, compound 1 showed absorptions at 320 and 390 nm in the UV region and a broad absorption around 450-600 nm, resulting in a reddish-brown color. Upon additions of 0.5 and 1.0 equiv. of MB, a broad absorption over the near-infrared region was observed (λmax = 1400 nm), turning a green solution. Further addition of MB up to 2.0 equiv. decreased the absorption around 1400 nm and absorptions at 615 and 970 nm appeared, and the solution turned blue (Fig. 4b). These results are similar to those reported by Yamago et al.27,28,29,30,31 about the formation of cation radicals ([6]CPP+·) (λmax = 1136 nm) and dication ([6]CPP2+) (λmax = 464, 792 nm) in the multi-step oxidation of [6]CPP by (NO)SbF6 (nitrosonium hexafluoroantimonate). The time-dependent density functional theory (TD-DFT) calculations suggested the formation of radical cation (1+·) (λDFT = 1334 nm) and dication (12+) (λDFT = 971 nm), respectively. The electron density difference of the first excited states in both 1+· and 12+ from those of [6]CPP+· and [6]CPP2+ suggests an electron donation from the methoxy groups regarding the red shifts of the absorption bands (Supplementary Tables 4–6).

Fig. 4: Chemical oxidation of [6]CPP-12OMe (1) with [N(C6H4−4-Br)3]SbCl6 (Magic Blue, MB).
figure 4

a Reaction scheme. b Ultraviolet/visible/near-infrared (UV/vis/NIR) titration of 1 with MB (CH2Cl2, [1] = 1.5 × 10–5 M, r.t.). c Two-dimensional nucleus-independent chemical shifts (2D NICS) grid of dication (12+). d NICS scan relative to y-axis. e NICS scan values relative to z-axis. f ORTEP drawing of 12+ (30% level of probability for thermal ellipsoids; gray, carbon; red, oxygen; light green, chlorine; antimony, purple). Hydrogen atoms are omitted for clarity. Source data are available as a Source data file.

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The formation of dication (12+) was also confirmed by 1H NMR spectroscopy. The chemical shift of the arylene protons was shifted from 7.34 ppm to 5.74 ppm by addition of 2 equiv. of MB (CDCl3, 298 K, Supplementary Fig. 20), which is due to the shielding effect caused by a generation of an in-plane aromaticity28. The results of the nucleus-independent chemical shifts (NICS) calculation also support the in-plane aromaticity of the oxidized species (Fig. 4c). The NICS value at the center of the macroring was strongly negative (–16.1 ppm), suggesting a strong diatropic ring current induced throughout the entire cavity due to the formation of in-plane aromaticity (Fig. 4d). Furthermore, negative NICS values over 10 Å along the perpendicular directions (z-axis) from the macroring suggest that the induced magnetic field extends also in the z-axis direction due to the ring current on the macroring (Fig. 4e).

A single crystal of the 12+ was obtained by vapor diffusion (1,2-dichloroethane/n-hexane), and the structure was successfully analyzed by X-ray crystallography (Fig. 4f). This is the smallest ring-sized CPP dication that has been successfully determined by X-ray crystallography, although Yamago et al. reported the crystal structure of [8]CPP dication27. The harmonic oscillator model of aromaticity (HOMA) value of each 6-membered ring in 12+ was calculated to be 0.585, which was a significant decrease of more than 0.3 over those of the neutral species 1 (0.895), indicating that the benzene rings in the dication adopt a quinoid-like structure resulting in the loss of aromaticity of the benzene ring. The bond alternation analysis of 1 and 12+ revealed that the arylene units of 12+ prefers a quinoid-like structure rather than quinone-like structure. According to the study on the oxidation of (C6H4−2,5-(OMe)2)nH2 (n = 2-9) by Rathore et al.33, the linear oligomers favored the quinone-like structure with the large dihedral angle, and the positive charge being localized to a part of the arylene ring(s), which are in contrast with the results of 12+.

Host-guest chemistry of [6]CPP-12OMe

[6]CPP-12OMe (1) adopts the cylindrical molecular structure with extremely electron-rich aryl rings owing to the multi-substituted methoxy groups, promising applications in host-guest chemistry. First, to investigate the scope of guest applicability for 1, we have mixed 1 and various guest molecules in CDCl3 and found that the chemical shift of the Ar-H protons changed significantly toward n-alkanes with an electron-deficient group such as cyano, N-pyridinium, azide, and isocyanate groups. On the other hand, mixing with guest molecules with branched chains (e.g. cyanoalkanes with branched chains, and trialkylammonium salts) and with electron-rich molecules (e.g., triglyme) did not affect the chemical shift of the Ar-H protons (Supplementary Figs. 24–26).

The complexation of 1 with NC-(CH2)4-CN (adiponitrile, G1) was confirmed by 1H NMR titrations (Fig. 5a). The addition of G1 upon a CDCl3 solution of 1 (0.5 mmol L–1, 298 K) caused a downfield shift of the 1H NMR signals of aryl and methoxy protons (Fig. 5b), indicating the formation of a supramolecular complex with a faster equilibrium rate than the 1H NMR timescale. The association constant (Ka) was estimated to be 186 M–1 (CDCl3, 298 K)39. The change in chemical shift would be caused by deshielding of protons due to a decrease in the dihedral angles (θ) accompanying a guest inclusion, rather than by an electrostatic interaction between the host and guest molecules.

Fig. 5: Host-guest chemistry of [6]CPP-12OMe (1).
figure 5

a Formation of inclusion complex (1⊃G1) between 1 and NC-(CH2)4-CN (adiponitrile, G1). b 1H NMR titration of 1 with G1 (400 MHz, CDCl3, r.t.). c Interaction energy decomposition by symmetry-adapted perturbation theory (SAPT) calculation of 1⊃G1 with different positions and orientations of G1 relative to 1 (SAPT0/jun-cc-pVDZ level of theory). d ORTEP drawing of inclusion complex (1⊃G1) (30% level of probability for thermal ellipsoids; gray, carbon; red, oxygen; G1 inside of the cavity of 1, blue; G1 inside of the cavity of 1, pink). Hydrogen atoms are omitted for clarity.

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Use of symmetry adaptive perturbation theory (SAPT) calculations40 with PSI441 to decompose the interaction energies for different conformations and positions of G1 in the inclusion complex (1⊃G1) showed that having G1 located inside the cavity with the gauche-conformation brings the CH2 unit closer to the arylene unit, which affects the electrostatic and dispersion forces more effectively than the anti-conformation (Fig. 5c). In addition, the gauche-conformation also enables a stronger electrostatic interaction between the terminal cyano group and electron-rich skeleton of 1 because of closer to each other than the anti-conformation. The closer guest-host contact enforces the dispersion force, which is in turn offset (to some extent) by the increased exchange repulsion.

A single crystal of the inclusion complex (1⊃G1) suitable for single crystal X-ray crystallography was obtained by slow diffusion of n-hexane vapor into a CHCl3 solution of 1 with an excess amount of G1 (Fig. 5d). The two enantiomers of 1 (pR and pS) and four G1 molecules are in an unit cell (P21/c). Two G1 molecules are located inside of the cavity of two 1 molecules with a gauche-conformation, whereas another two G1 molecules are located outside of the macrocycle with an anti-conformation. The averaged dihedral angle (θavg) of inclusion complex (1⊃G1) was estimated to be 9.86°, which is drastically reduced from that of 1,2-dichloroethane incorporated structure (24.2°) shown in Fig. 2c. The guest molecule inside the cavity of 1 adopts an entropically unfavorable the gauche-conformation, and multiple intermolecular CH-π interactions were formed between the alkyl hydrogens of G1 and the arylene rings of 1 (Supplementary Fig. 34c). These results suggest that the inclusion of G1 is enthalpy-driven process caused by the combination of dispersion and electrostatic interactions between host and guest molecules, which has been supported by the results of the SAPT calculations (Fig. 5c). This is the first example of CPP encapsulating a guest molecule with a flexible alkyl structure, which is achieved by the electron-rich arylene rings with the methoxy groups.

Rotaxane synthesis and its chemical oxidation

We then applied the function of [6]CPP-12OMe (1) as a supramolecular host to the synthesis of a mechanically interlocked molecule (MIM)42 with a planar chirality. Mixing 1 with an excess amount of OCN-(CH2)6-NCO (hexamethylene diisocyanate) in CHCl3 to form a pseudo[2]rotaxane in situ, then introducing a bulky substituent at both ends of the axle molecule through a urea bond formation reaction with 1-adamantanemethylamine produced a [2]rotaxane (2) containing 1 as a ring component (Fig. 6a). The chiral HPLC analysis of 2 observed two peaks with the retention times of 12.5 and 13.2 min, respectively (Supplementary Fig. 14b). This result indicates that the interpenetration of the alkyl chain to the cavity of 1 prevented the pR ⇔ pS racemization through a sequence of “oxygen-through-the-annulus” inside-out and outside-in rotations as seen in pillar[n]arene43.

Fig. 6: Synthesis and characterization of [2]rotaxane (2).
figure 6

a Synthetic route for 2. Molecular model of 2 was optimized by DFT calculations. Hydrogen atoms of CPP unit were omitted for clarity. b 1H NMR spectra (400 MHz, CDCl3, r.t.) of (i) [6]CPP-12OMe (1), (ii) axle compound (A) (the molecular structure is shown in the inset), and (iii) [2]rotaxane (2). c The distance change between the centroid of CPP macroring and outer nitrogen atom in the axle as a function of time during the molecular dynamics (MD) simulations. Source data are available as a Source data file.

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In the 1H NMR spectrum of racemate of 2 (Fig. 6b, iii), the chemical shifts of the CH2 protons of the axle component (Hc, Hd) were observed around 0.9 to –0.5 ppm, which are upfield region than that of axle compound (A) (Fig. 6b, ii). These shifts are attributed to the shielding effect from the arylene rings of 1, indicating that the alkyl chain is mechanically interlocked inside the cavity of 1. On the other hand, one of the NH protons of the urea groups shifted significantly to a downfield position at 5.79 ppm, which is due to the formation of NH…O hydrogen bonds between NH proton and methoxy oxygens of 1. The formation of NH…O hydrogen bonds was also observed in the stable conformation of 2 as estimated by DFT calculations (Fig. 6a). These results suggest that the terminal urea groups function as a “station”, and that the CPP macrocycle undergoes a rapid shuttling movement along the alkyl chain of the axle component, which is also supported by the molecular dynamics (MD) calculations (Fig. 6c and Supplementary Movie 1). von Delius et al. reported the synthesis of [2]rotaxane with [10]CPP as the ring component and fullerene (C60) as the axle and the endcap groups44. In that case, the CPP macrocycle mainly rotates around C60 moiety because of the strong interaction between [10]CPP and C60. Recently, Jasti et al. successfully synthesized a [3]rotaxane with two N-doped [8]CPPs as the ring component and an axle component consisting of 1,4-phenylene and ethynylene groups, utilizing an active template method45. As there are no stations incorporated in the axle component, the CPP units are assumed to be shuttling freely along the axial molecule. Thus, we succeeded in developing a new CPP-based molecular machine that imparts a higher order of mechanical motion by utilizing the interaction between methoxy groups introduced into [6]CPP and the urea moieties of the axle component. This molecule offers the potential for a new supramolecular system utilizing its planar chiral mechanically interlocked structure, redox ability of CPP unit, and an anion-binding property of urea moieties46.

We have successfully achieved the selective two-electron oxidation of the ring component within the [2]rotaxane (2), without decomposition of other component, by adding 2 equivalents of MB as a mild oxidant owing to the low oxidation potential of [6]CPP-12OMe (1) (Fig. 7a). Remarkably, two-electron oxidation of 2 causes significant upfield shift of the 1H NMR signals of the methylene protons of the axle molecule to –4.6 (Hb), –8.9 (Hc), and –14.5 (Hd) ppm, respectively (Fig. 7b). There significant upfield shifts can be ascribed to the shielding effect by a diatropic ring current on the CPP macroring, leading to the appearance of the above-mentioned in-plane aromaticity (Fig. 4c). In previous studies on CPP dications, the presence of in-plane aromaticity has been indirectly speculated from the chemical shifts of the aryl protons located in the perpendicular position of the macrorings27,28,29,30. However, it was not clear whether these changes in chemical shifts were due to the diatropic ring current caused by the in-plane aromaticity or the formation of the cyclic quinoid structures. Anderson et al. have demonstrated the in-plane aromatic/anti-aromatic nature of multiply oxidized porphyrin nanorings, as evidenced by the chemical shifts of pyridyl hydrogen in hexa(4-pyridylethynyl)benzene, which was incorporated within the nanoring′s interior47,48. However, the environment at the center of the nanoring could not be evaluated for the chemical shifts of the pyridyl hydrogens, as they are positioned in close proximity to the nanoring by coordinating to the porphyrin groups. In this study, we present the first experimental evidence of the in-plane aromaticity in the center of the macrocycle, as indicated by the chemical shifts of protons of the interlocked alkyl chain threaded in the perpendicular direction to the CPP macrocycle. Furthermore, the sequential downfield shift in the 1H NMR signals of the methylene protons from the central position along the urea side (Hd: –14.5 ppm → Hc: –8.9 ppm → Hb: –4.6 ppm) provides experimental evidence for decreasing shielding of the in-plane aromaticity along the perpendicular (z-axis) direction to the CPP macroring (Fig. 7b, inset).

Fig. 7: Chemical oxidation of [2]rotaxane (2).
figure 7

a Reaction scheme. b 1H NMR spectra (400 MHz, CDCl3, r.t.) of [2]rotaxane (2) before (top) and after (bottom) chemical oxidation upon addition of 2 equivalents of Magic Blue (MB). Inset: plausible illustration of the shielding area of the in-plane aromaticity based on the chemical shifts of the alkyl chain.

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Methods

General

All manipulations were carried out under an argon atmosphere using standard Schlenk techniques. The 1H, 13C{1H}, and 31P{1H} NMR spectra were recorded on a Bruker Biospin AVANCE NEO 400 (400 MHz), Bruker Biospin AVANCE II DPX-400 (400 MHz), Bruker AscendTM 400 (400 MHz), or JEOL ECZ400S (400 MHz). The chemical shifts in 1H and 13C{1H} NMR were referenced with respect to TMS (1H NMR; δ 0.00 for CDCl3) or residual peaks of the solvents used (13C NMR; δ 77.16 for CDCl3). The peak positions of the 31P{1H} NMR spectra were referenced to external 85% H3PO4 (δ 0.00) in deuterated solvents). Column chromatography was performed on silica gel 60 (spherical, neutral) with particle size of 40-63 μm (YMC), or 40-100 μm (Kanto), or 100-210 μm (Kanto). Deuterated solvents were purchased from Kanto or ISOTEC and used as received. Chiral HPLC analysis were conducted on an instrument equipped with a JASCO PU-4185 HPLC pump, JASCO UV4575 UV/Vis detector, and a DAICEL CHIRALPAK® IA column (10 mm × 250 mm). Elemental analyses were performed using a J-Science JM10. The high-resolution mass spectrometry (HRMS) was measured in Spiral mode (positive) on a JEOL JMS-S3000 SpiralTOF (MALDI-TOF). Cyclic voltammetry (CV) was measured in CH2Cl2 solutions containing 100 mM nBu4NPF6 with ALS electrochemical analyser Model-600A. The measurement was carried out in a standard one compartment cell equipped with a Ag/Ag+ reference electrode, a platinum wire counter electrode, and a platinum disk working electrode. UV-Vis-NIR absorption spectra were obtained on a SHIMADZU UV-3150PC spectrophotometer.

The commercially available reagents, HAuCl4·4H2O (Tanaka, purity: >99.8%), tetrahydrothiophene (TCI, purity: >99.0%), bis(dicyclohexylphosphino)methane (Wako, purity: 95 + %), 1-bromo−2,5-dimethoxybenzene (Aldrich, purity: 98%), 2,5-dimethoxyphenylboronic acid (Wako, purity: >97 + %), NBS (Kanto, purity: >98.0%), n-BuLi in 1.6 M n-hexane solution (Kanto, purity: >98.0%), B(i-OPr)3 (Aldrich, purity: ≥98%), Cs2CO3 (Wako, purity: 95.0 ~ 102.0%), Magic Blue (MERCK, technical grade), hexamethylene diisocyanate (TCI, purity: >98.0%), 1-adamantanemethylamine (TCI, purity: >98.0%), were used as received. [Pd(PPh3)]4 was prepared by hydrazine reduction of a mixture of PdCl2 and PPh3. PhICl2 was prepared from the oxidation of iodobenzene by Cl2, which was generated in situ from the reaction of 5% NaClO aq. (commercial household bleach) with conc. HCl. [Au2Cl2(dcpm)] (dcpm = bis(dicyclohexylphosphino)methane) was prepared by the ligand exchange reaction of [AuCl(tht)] (tht = tetrahydrothiophene) with 0.5 molar amount of dcpm (Supplementary Method 1). (2,2′,5,5′-Tetramethoxy-[1,1′-biphenyl]−4,4′-diyl)diboronic acid (L1) was synthesized by the Suzuki coupling reaction of 1-bromo−2,5-dimethoxybenzene with 2,5-dimethoxyphenylboronic acid, followed by bromination and borylation at the 4,4′-position (Supplementary Methods 2–4).

Synthesis of macrocyclic Au complex (Au-1)

A mixture of L1 (0.87 g, 2.4 mmol), Cs2CO3 (4.71 g, 14.4 mmol) and [Au2Cl2(dcpm)] (2.11 g, 2.4 mmol) in degassed toluene/ethanol/water (100 mL/25 mL/25 mL) was stirred for 20 hours at 50 °C under argon atmosphere. After the reaction mixture was allowed to cool to room temperature, the precipitate was collected by suction filtration. The crude product was purified by recrystallization (CHCl3/n-hexane = 10 mL/40 mL) to afford Au-1 as a white solid (2.15 g, 0.67 mmol, 84%).

¹H NMR (400 MHz, CDCl3, 297 K): δ 7.17 (t, J = 3.1 Hz, 6H, Ar-H), 6.75 (s, 6H, Ar-H), 3.70 (s, 18H, OCH3), 3.31 (s, 18H, OCH3), 2.29-2.18 (br, 12H, C6H11, CH2), 2.14-2.07 (br, 24H, C6H11), 2.07-1.97 (br, 12H, C6H11), 1.92-1.85 (br, 24H, C6H11), 1.78-1.69 (br, 18H, C6H11), 1.69-1.63 (br, 12H, C6H11), 1.30-1.25 (br, 36H, C6H11).

¹³C{¹H} NMR (100 MHz, CDCl3, 297 K): δ 161.58 (t, J = 54.9 Hz), 152.23 (s), 126.69 (s), 124.77 (s), 115.74 (s), 57.97 (s), 56.60 (s), 35.45 (t, J = 14.2 Hz), 29.92 (s), 29.16 (s), 26.98 (t, J = 6.96 Hz), 26.14 (s).

³¹P{¹H} NMR (161 MHz, CDCl3, 297 K): δ 48.44 (s)

Anal. Calcd for C123H186O12Au6P6 + CHCl3: C, 44.54; H, 5.64. Found: C, 44.93; H, 5.81.

Synthesis of [6]CPP-12OMe (1)

To a suspension of Au-1 (97.4 mg, 30 μmol) in degassed DMF (20 mL) was added PhICl2 (26.4 mg, 96 μmol) in DMF (10 mL) dropwise with stirring at –60 °C for 30 min under an argon atmosphere in the dark. The reaction mixture was stirred at the same temperature for 30 min, then it was allowed to warm to 25 °C and stirred for 5 h in the dark. Solvent and iodobenzene (by-product) were removed under vacuum. The crude product was purified by silica gel column chromatography in the dark (eluent; CHCl3/AcOEt = 10:1, Rf = 0.6) gave 1 (11.0 mg, 13.5 µmol, 45%) as an orange solid.

¹H NMR (400 MHz, CDCl3, 297 K): δ 7.33 (s, 12H, Ar-H), 3.71 (s, 36H, OCH3)

¹³C{¹H} NMR (100 MHz, CDCl3, 297 K): δ 152.39 (s), 126.21 (s), 115.65 (s), 57.22 (s)

HRMS (MALDI-TOF, DCTB; Ionizer, NaTFA): calcd. for C48H48O12: 816.3140, found: m/z 816.3159 ([M]·+).

Synthesis of [2]rotaxane (2)

To a CHCl3 solution (3 mL) of [6]CPP-12OMe (1) (51.8 mg, 63 μmol) and hexamethylene diisocyanate (529 mg, 3.1 mmol) was added 1-adamantanemethylamine (1.19 g, 7.2 mmol) at 0 °C, and stirred for 10 min at the same temperature in the dark. After the reaction mixture allowed to warm to r.t., CHCl3 (6 mL) was added the reaction mixture. The resulting white solids was removed by suction filtration. The filtrate was purified by silica gel column chromatography twice in the dark (eluent; CHCl3/AcOEt = 10:3, Rf = 0.24) to give [2]rotaxane (2) (2.1 mg, 1.6 µmol, 3.0%) as a dark orange solid.

¹H NMR (400 MHz, CHCl3, 297 K): δ 8.28 (s, 12H, Ar-H), 5.79 (t, J = 6.1 Hz, 2H, NH), 4.58 (t, J = 4.6 Hz, 2H, NH), 4.02 (s, 36H, OCH3), 3.26-3.10 (m, 4H, CH2), 2.12-2.06 (br, 6H, C10H15), 1.85-1.66 (br, 24H, C10H15), 0.65-0.51 (br, 4H, CH2), –0.39 - –0.50 (br, 4H, CH2).

HRMS (MALDI-TOF, DCTB; Ionizer, NaTFA): calcd. for C78H98O4N4O14: 1314.7074, found: m/z 1314.7074 ([M]·+).

Chemical oxidation of [2]rotaxane (2)

To a CDCl3 solution (0.7 mL) of [2]rotaxane (2) (2.1 mg, 1.6 μmol) was added Magic Blue (2.9 mg, 3.5 μmol, 2 equiv.) under an argon atmosphere. The 1H NMR spectrum of this sample was measured (Fig. 7).