Hierarchical Assembly of an Interlocked M₈L₁₆ Container

Abstract

The self‐assembly of eight Pd^II cations and sixteen phenanthrene‐derived bridging ligands with 60° bite angles yielded a novel M₈L₁₆ metallosupramolecular architecture composed of two interlocked D _4h‐symmetric barrel‐shaped containers. Mass spectrometry, NMR spectroscopy, and X‐ray analysis revealed this self‐assembled structure to be a very large “Hopf link” catenane featuring channel‐like cavities, which are occupied by NO₃ ⁻ anions. The importance of the anions as catenation templates became imminent when we observed the nitrate‐triggered structural rearrangement of a mixture of M₃L₆ and M₄L₈ assemblies formed in the presence of BF₄ ⁻ anions into the same interlocked molecule. Furthermore, the densely packed structure of the M₈L₁₆ catenane was exploited in the preparation of a hexyloxy‐functionalized analogue, which further self‐assembled into vesicle‐like aggregates in a reversible manner.

Mechanically interlocked structures continue to spark scientific interest and curiosity owing to their aesthetic appeal and the dynamic properties that are introduced by the mechanical bond.1 Although their preparation initially posed a synthetic challenge, the utilization of molecular templates2 and the implementation of reversible covalent bonds3 have resulted in high‐yielding and facile syntheses. In this regard, the highly directional coordinative bond has been the basis of a variety of interpenetrated structures, such as catenanes,4 rotaxanes,5 knots,6 Borromean rings,7 and more.8

Among the plethora of possible metal and ligand combinations, Pd^II cations together with N‐donor bridging ligands represent a robust and reliable combination widely utilized in the formation of hollow and interlocked metallosupramolecular structures.8b, 9 For assemblies obeying Pd_nL_2n stoichiometry (n=6, 12, 24, 30 …), Fujita and co‐workers have demonstrated the topological dependence of the structure of hollow polyhedra on obtuse ligand bite angles.10 This work was recently expanded to the synthesis of a giant Pd₄₈L₉₆ Goldberg polyhedron.10e More acute ligand bite angles (≥60°) often yield Pd₃L₆ and Pd₄L₈ barrel‐shaped containers or Pd₄L₈ doubly bridged tetrahedra (Figure 1),11 whilst ligands with a parallel orientation of donors form lantern‐shaped Pd₂L₄ coordination cages.9 Catenation of the latter cages results in a larger family of Pd₄L₈ dimeric structures with a partitioned cavity capable of allosterically binding charged12 and neutral13 guest molecules. Under certain circumstances, these types of ligands also form a triply catenated link.14 More recently, the close proximity of electron donor/acceptor moieties in mixed‐ligand Pd₄L₈ interpenetrated cages has been exploited to study charge‐transfer phenomena,15 demonstrating that interlocked structures can also serve as platforms to examine interactions of densely packed functionalities.

Figure 1.

Comparison of the known M_nL_2n (M=Pt^II or Pd^II) structures according to the bite angle of their constituent ligands with the catenated M₈L₁₆ architecture 2. Metal‐mediated self‐assembly of a ligand with a 60° bite angle can give rise to M₃L₆ (1 a) or M₄L₈ structures (1 b or 1 c). In previous studies, only M₂L₄ cage structures were shown to undergo catenation to give M₄L₈ interlocked dimers.

Despite the vast structural diversity of reported Pd_nL_2n polyhedral structures, interpenetrated assemblies larger than the Pd₄L₈ dimeric cages remained hitherto undiscovered. Herein, we report the assembly of an interlocked metallosupramolecule with the formula M₈L₁₆ (M=Pd^II), which is the largest Pd_nL_2n catenane reported to date. Palladium‐mediated self‐assembly of the dimeric structure was achieved with Pd(NO₃)₂ and a rigid bis(monodentate) ligand L with a bite angle of 60°. The presence of NO₃ ⁻ anions is crucial for the formation of the large catenane, and can also trigger the structural rearrangement of a mixture of Pd₃L₆ and Pd₄L₈ assemblies formed in the presence of BF₄ ⁻ anions into the same interpenetrated structure. Through alkyl functionalization of the ligand backbone, an amphiphilic catenane was prepared that further self‐assembled into vesicle‐like aggregates, demonstrating that the densely packed nature of the Pd₈L₁₆ architecture can be utilized as a platform for higher‐order supramolecular aggregation.

Phenanthrene‐based ligand L¹ (Figure 2) readily underwent self‐assembly with [Pd(CH₃CN)₄](BF₄)₂ to form a D _4h‐symmetric Pd₄L₈ (1 b) container in DMSO as the only product.11c In CD₃CN, however, a 1:2:0.2 mixture of a D _3h‐symmetric Pd₃L₆ (1 a) container, 1 b, and a D _2d‐symmetric tetrahedron (1 c) was obtained (Figure 1).16 As both solvent and anion are known to dramatically affect the assembly of coordination cage structures,9d, 11 we carried out further investigations, including the reaction of L¹ with Pd(NO₃)₂. Self‐assembly in the presence of nitrate anions again yielded 1 b as the major product in DMSO (Figure S10); however, in CD₃CN, we observed an entirely different outcome.

Figure 2.

Top: Reaction equation representing the formation of Pd₈L₁₆ (2 a–2 c). Bottom: ¹H NMR spectra (500 MHz, CD₃CN, 25 °C) of a) ligand L¹ and b) 2 a. c) ESI‐MS spectrum of 2 a with the measured and calculated isotope patterns of [2 a+9 NO₃]⁷⁺ shown in the inset.

Heating a 2:1 mixture of L¹ and Pd(NO₃)₂ in CD₃CN at 70 °C for 24 h resulted in the quantitative formation of a new species (2 a), as indicated by ¹H NMR spectroscopy and ESI mass spectrometry. In the ¹H NMR spectrum, a total of 20 aromatic signals were identified in the range of δ=6.6–10.7 ppm (compared with 5 aromatic signals for L¹), along with four signals in the region of the methoxy protons (Figures 2 and S11). ESI‐MS analysis gave a spectrum with several prominent peaks consistent with the formula [Pd₈L¹ ₁₆+n NO₃]^(16−n)+ (n=7–12; Figure 2 c). By COSY NMR analysis, we identified four distinct sets of aromatic signals of equal ratios for L¹. Further analysis by ¹H‐¹H NOESY revealed numerous cross‐peaks (Figure S14), including notable through‐space contacts between the H_c protons of sets 1/2 and 3/4. We therefore postulated that the fourfold splitting is due to L¹ being in two different chemical environments and losing its twofold symmetry in 2 a. The exclusive formation of 2 a was further confirmed by DOSY NMR analysis (Figure S16), which revealed that all of the assigned proton signals correspond to the same diffusion coefficient, with the derived hydrodynamic radius (1.24 nm) pointing towards a rather compact structure.

According to the empirical predictions for Pd_nL_2n assemblies,10 a structure with a composition of Pd₈L₁₆ is incompatible with a spherical, hollow topology, unless it is a transient intermediate towards larger Pd₁₂L₂₄ polyhedra.10d In light of the fourfold signal splitting observed in the ¹H NMR spectrum of 2 a, our Pd₈L¹ ₁₆ assembly is therefore likely to be composed of two interpenetrating Pd₄L¹ ₈ subunits. To gain insight into whether the possible monomeric Pd₄L₈ assemblies (1 b or 1 c) are transient intermediates preceding 2 a, time‐resolved ¹H NMR experiments were performed on a 2:1 mixture of L¹ and Pd(NO₃)₂ at 70 °C in MeCN (Figure S17). Only the proton resonances of 2 a evolved gradually over 20 h, and no other species were detected, suggesting that any intermediates involved in the self‐assembly process are polymeric or short‐lived in solution.

Owing to difficulties encountered with obtaining crystals of 2 a that are suitable for X‐ray analysis, we focused on modifying the solubility of the catenane by utilizing a propoxy‐functionalized ligand L². Under the same reaction conditions as for 2 a, the reaction of L² with Pd(NO₃)₂ gave an analogous Pd₈L₁₆ interlocked structure (2 b), as confirmed by ¹H NMR spectroscopy and ESI‐MS analysis (Figures S18–S21). Single crystals (diffracting up to 1.28 Å with synchrotron radiation)17 were grown by slow vapor diffusion of diisopropyl ether into a concentrated CD₃CN solution of 2 b, enabling unambiguous structure elucidation by X‐ray crystallography. 2 b crystallized in the monoclinic space group P2₁/n, with one Pd₈L₁₆ molecule in the asymmetric unit. The large interpenetrated structure, which is composed of two interlocked D _4h‐symmetric containers,18 can be described as a “Hopf link” (Figure 3) with D _2d symmetry.

Figure 3.

X‐ray structure of 2 b:24 a) Showing Pd⋅⋅⋅Pd distances and encapsulated NO₃ ⁻ anions along the major C₂ axis, b) highlighting the Pd⋅⋅⋅Pd distances of cations orthogonal to the major C₂ axis, c) a space‐filling representation of the [2]catenane with NO₃ ⁻ anions removed for clarity.

In the structure of 2 b, the Pd₄L₈ monomers are geometrically related to one another by a 90° rotation along the major C ₂ axis, creating an even partition of three channel‐like cavities, each accommodating a NO₃ ⁻ counterion (Figure 3 a). The central cavity is enclosed by phenanthrene moieties of L², which participate in offset π‐stacking with an average separation of 3.7 Å. In contrast to the Pd₄L₈ interpenetrated cages,8b 2 b appears to be sterically restricted from mechanical movement owing to the respective tilt of the ligands between adjacent Pd₄L₈ units. In addition to the three NO₃ ⁻ anions found along the C₂ axis, four more (of a total of 13 located in the Fourier difference map) were found within the interpenetrated structure; however, not all of them occupied defined cavities. For example, 2 b contains four smaller cavities located perpendicular to the major C ₂ axis along the Pd₃ planes (Figure 3 b), with only two of the four cavities being occupied. Accordingly, the Pd⋅⋅⋅Pd separations for the empty cavities are 0.2–0.5 Å shorter than those of the filled cavities.19

Next, we examined whether NO₃ ⁻ anions trigger a transformative rearrangement of the mixture of 1 a, 1 b, and 1 c that is formed when L¹ is reacted with [Pd(CH₃CN)₄](BF₄)₂ 16 in CD₃CN (during the course of our studies, a single crystal of 1 c was isolated and analyzed by X‐ray crystallography, further supporting 1 c as one of the Pd‐mediated assemblies of L¹; Figures 4 b and S38–S40). The mixture of 1 a, 1 b, and 1 c was therefore heated at 70 °C for 24 h with 4, 8, and 12 equivalents of NO₃ ⁻. In each case, ¹H NMR spectroscopy revealed that 2 a was formed exclusively (Figure 4); however, the reaction proceeded with the highest yield when 8 equivalents of NO₃ ⁻ were used (Figure S27). ESI‐MS of this sample confirmed the structural conversion of 1 a–1 c into 2 a as it revealed signals corresponding to [Pd₈L¹ ₁₆+n X]^(16−n)+ (n=8–11, X=Cl⁻, NO₃ ⁻, and BF₄ ⁻), with each signal distribution comprising a bias towards X=8 NO₃ ⁻ and (8−n) BF₄ ⁻ (Figure S28). To gain further insight into the role of the nitrate anions in the system, we performed the same transformation with a ¹⁵N‐labeled NO₃ ⁻ source. Inverse‐gated ¹⁵N NMR analysis revealed a single ¹⁵N signal, which corresponds to the free ¹⁵NO₃ ⁻ signal of the tetrabutylammonium salt used in the transformation (Figure S29). This indicates that the NO₃ ⁻ anions are not tightly bound and are free to exchange with free NO₃ ⁻ in the solvent, which is consistent with the channel‐like cavities observed in the X‐ray structure of 2 b. The reason for why catenation is observed only in the presence of NO₃ ⁻ anions could therefore be related to their optimal size as templates for this dimer.12b, 14, 20 Indeed, 1 a–1 c were not transformed into the catenated product upon extended heating (70 °C, 24 h) or in the presence of PF₆ ⁻ anions (Figures S9 and S31).

Figure 4.

a) The NO₃ ⁻‐mediated transformation of 1 a–1 c into 2 a. b) X‐ray structure of 1 c.24 c) ¹H NMR spectra (500 MHz, CD₃CN) of i) 1 a–1 c and ii) the same mixture after heating for 24 h in the presence of NO₃ ⁻ anions.

Finally, we examined whether the structurally dense nature of the Pd₈L₁₆ [2]catenane can be utilized as a platform for further functionalization and supramolecular aggregation. It is worth noting that hierarchical aggregates of nanocages have scarcely been reported, and the underlying mechanisms of such systems primarily rely upon counterion‐mediated interactions and π‐stacking.21 To promote a different aggregation pathway, we prepared a dihexyloxy‐functionalized ligand (L³) for the palladium‐mediated self‐assembly of amphiphilic catenane 2 c (Figures S22–S26). Remarkably, in MeCN, 2 c rapidly and spontaneously further self‐assembled into a colloid of nanoscalar vesicular aggregates by virtue of the dense hydrophobic interactions between molecules of 2 c (Figure 5). This is in contrast to the behavior of 2 a and 2 b, which remain in solution owing to the shorter alkyl chains of their respective ligands. At 25 °C, a ¹H NMR spectrum of a cloudy solution of 2 c revealed the complete absence of proton resonances. At elevated temperatures (50–70 °C), however, the solution of 2 c became completely transparent, and the characteristic NMR spectroscopic signature of the interlocked molecule was observed (Figures S22 and S23). Dynamic light scattering (DLS) analysis of 2 c revealed particles with diameters of 150±45 nm (PDI=0.09) at 20 °C, which were observed to incrementally swell upon dilution (Figure S32), which is indicative of a vesicular‐type assembly.22 Variable temperature (VT) DLS revealed that this aggregate begins to disassemble between 40 and 50 °C, at which point a smaller aggregate (36.2±20.4 nm) is formed along with particles measuring 2.3±0.7 nm in diameter, the latter coinciding with the approximate dimensions of a single molecule of 2 c. Interestingly, cooling the sample back to 20 °C resulted in the recovery of the original, approximately 150 nm large aggregate (Figure 5 a), with the MeCN solution becoming cloudy once again. The reversibility of the temperature‐dependent supramolecular aggregation was demonstrated over three cycles by DLS with no detectable degradation (Figure S33). High‐resolution TEM analysis of 2 c (Figures 5 b and S34) confirmed the presence of spherical particles, albeit with a slightly broader distribution (80–200 nm).23 This is in contrast to the TEM analysis of 2 a, which revealed small particles with diameters of approximately 3 nm, which correspond to non‐aggregated molecules of 2 a (Figure S36). This observation further supports our hypothesis that the hydrophobic hexyloxy chains in 2 c promote hierarchical aggregation, which is facilitated by the structurally dense nature of this type of interlocked architecture.

Figure 5.

a) Variable‐temperature DLS. b) TEM images of 2 c. c) Temperature‐dependent aggregation of 2 c (plausible model based on the X‐ray structure of 2 b).

In conclusion, we have reported the self‐assembly of a 24‐component Pd₈L₁₆ [2]catenane composed of two interlocked D _4h‐symmetric Pd₄L₈ barrel‐shaped containers. The formation of the large catenane was shown to depend on the presence of NO₃ ⁻ counterions by NMR, ESI‐MS, and crystallographic analysis. We also showed that NO₃ ⁻ anions can trigger the structural rearrangement of a mixture of Pd₃L₆ and Pd₄L₈ assemblies into the same interpenetrated product. Indeed, the X‐ray crystal structure of 2 b revealed that the channel‐like cavities are occupied by NO₃ ⁻ anions, which not only charge‐balance the structure but also facilitate the interpenetration of the Pd₄L₈ barrel‐shaped monomers. Exohedral functionalization of the structurally dense catenane with hexyloxy chains resulted in the hierarchical assembly of vesicle‐like aggregates, which could be reversibly assembled and disassembled by a change in temperature. We are currently investigating the use of this aggregate as a molecular delivery and release vessel.

Conflict of interest

The authors declare no conflict of interest.

Supporting information

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Supplementary

W. M. Bloch, J. J. Holstein, B. Dittrich, W. Hiller, G. H. Clever, Angew. Chem. Int. Ed. 2018, 57, 5534.