Structural Transformations in Coordination Cages

6.13

Structural Transformations in Coordination Cages

MD Johnstone and GH Clever, TU Dortmund University, Dortmund, Germany Ó 2017 Elsevier Ltd. All rights reserved.

6.13.1 Introduction 6.13.2 Small Molecule-Induced Changes 6.13.2.1 Variation of Metal: Ligand Stoichiometry 6.13.2.2 Solvent Responsive Systems 6.13.2.3 Guest-Induced and Template Driven Changes 6.13.2.3.1 Structural transformations 6.13.2.3.2 Transformations between monomeric and dimeric cages 6.13.2.3.3 Halide-responsive allosteric processes in interpenetrated cages 6.13.2.4 Action of Competitive Ligands 6.13.2.4.1 Halide-triggered structural reorganization 6.13.2.5 pH-Induced Changes 6.13.3 Redox-Induced Changes 6.13.4 Light-Induced Changes 6.13.4.1 Switching of Guest Binding 6.13.4.2 Light-Triggered Structural Reorganization 6.13.5 Conclusion Acknowledgments References

6.13.1

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Introduction

The implementation of supramolecular chemistry principles is essential in the development of manmade chemical systems and novel materials showing a high degree of structural and functional complexity.1 While decades of research in the areas of inorganic, organic and polymer materials have led to a large variety of functional materials based on covalent and coordination bonds, the rational use of noncovalent interactions in bulk materials based on supramolecular entities is still in its infancy. In contrast to the top-down synthetic approaches frequently employed to produce nanostructured surfaces and particles, supramolecular bottom-up strategies allow for formation of materials of defined composition and morphology with fine-tuned functionalities positioned with atomic precision. In this sense, methods aimed at increasing the complexity of synthetic systems has led to the emergence of materials with novel features and useful functions. Such materials promise a variety of future applications, e.g. as photoactive layers in heterojunction solar cells, as selective adsorbents or catalysts, as matrices for biomedical purposes (drug deliverers, diagnostic tools or scaffolds in regenerative tissue engineering) and in molecular electronics and magnetism, to name but a few. Nature consists of many diverse molecular scaffolds such as 1D helices (DNA), 2D surfaces (lipid membranes), and 3D structures of irregular (most proteins) or regular shape (virus capsids). Such biological systems are highly complex and involve intricate signaling processes and the dissipative maintenance of a network of coupled equilibria, fundamental for sustaining life. Biological systems use a combination of covalent bond forming reactions (within smaller building blocks and between the monomers of the biopolymers) combined with various noncovalent interactions to build up complex structures. Likewise, the predominant assembly forces involved in synthetic supramolecular systems based on discrete organic building blocks are noncovalent interactions (e.g., H-bonding, halogen bonding, p-interactions, and Van der Waals forces) in conjunction with dynamic covalent chemistry and coordination chemistry. The majority of examples involve a combination of noncovalent interactions that contribute to the system’s stability and behavior. Self-healing features, stimuliresponsiveness, and regulated catalytic processes are just some of the sophisticated attributes that nature has perfected. Nature’s astonishing level of complexity and efficiency has captivated chemists, and has inspired work to re-engineer and mimic a variety of biological processes. Although matching Nature’s accomplishments is a formidable challenge, and many aspects are distant goals, an impressive amount of progress has been achieved to date. Accordingly, the development of synthetic systems responsive to external stimuli such as light, pH, guest molecules, or specific reagents remains a challenging task. Coordination-driven architectures are an important class of artificial self-assembled structures, and the principle of metal-mediated self-assembly has been established as a powerful method to provide highly complex and functional supramolecular entities. Indeed, self-assembly is a major strategy in the construction of such systems, as the careful selection of simple molecular building blocks can readily generate complex molecular architectures under thermal equilibrium conditions. This self-assembly approach enables a high level of complexity to be achieved with relative ease, and at the same time imbues specific features.

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A self-assembled coordination structure comprises two or more ligands anchored by multiple metal ions. Depending on their shape, discrete (nonpolymeric) assemblies can be subclassified into several groups including ring structures (also comprising knots, catenanes, and rotaxanes), tubes, cages (containing cavities with open portals enabling guest exchange), capsules (containing confined cavities), and spheres (large globular species). Notably, coordination cages are highly appealing on account of the internal cavities that are separated from the external solution, which provide a unique environment with respect to encapsulation of guest species.2 Transition metals such as palladium, platinum, iron, zinc, copper, silver, and titanium are most commonly employed as the metal nodes. However, cages using main group metals, lanthanides, or actinides have been reported but are much less common. The majority of coordination cages employ only one kind of metal and ligand, however, more recently numerous examples of selfassembled structures that contain more than one type of metal3 and/or ligand4 have been documented in the literature. In order to design functional, stimuli-responsive systems, one must incorporate the ability for a particular assembly not just to act as a host, but also to undergo dynamic structural changes in response to stimuli in the surrounding environment. Multicomponent coordination assemblies are known to alter their size or structure under such circumstances, examples of which include alteration of the reactant stoichiometries employed, as well as the solvent, counterion, or template present. There is particular interest in the control and modulation of the internal cavity environment of coordination cages. For example, such changes in the host–guest chemistry have facilitated the implementation of fascinating guest encapsulation phenomena, including cooperative binding and template-controlled selectivity. To date, a few examples of stimuli-responsive systems have been realized in which specific triggers exert a downstream control over the binding of additional guests or even effect complete structural transformations. By mastering the functional and structural complexity of self-assembled coordination cages, it is possible to accomplish and design novel biomimetic receptors and catalytic systems as well as intelligent materials. This chapter focuses on the structural changes and dynamic properties of self-assembled coordination cages, highlighting recent advances in stimuli-responsive systems. The discrete coordination architectures that are discussed are predominantly monomeric cages but also include examples of interpenetrated dimeric cages. Factors influencing the behavior of the cages are discussed, including flexibility and geometry of the ligands, the coordination environment, as well as external factors such as the effect of the counter anion, solvent, guest molecules, electrical potential, and light.

6.13.2

Small Molecule-Induced Changes

6.13.2.1

Variation of Metal: Ligand Stoichiometry

Besides the addition of extra stimuli, variation in the relative ratio of the cage-forming components, i.e., the ligand and the metal precursor, has already led to different assembly results. For example, Shionoya and Hiraoka reported a disk-shaped trismonodentate ligand in which methyl groups attached to the benzene core force the benzimidazoyl arms out of plane.5 Mixing the ligand with AgOTf resulted in either a rather flat [Ag3L2] triangular sandwich-like complex or a 3D [Ag4L4] tetrahedral cage. Both architectures were in a dynamic equilibrium in solution, and tuning the equilibrium was shown to be possible. When the M:L ratio was between 1:1 and 1:1.5, mixtures of the two species were present. However, a complete shift of the equilibrium toward the sandwich-type [Ag3L2] and tetrahedral [Ag4L4] species was achieved by altering the metal:ligand ratio to 3:2 and 1:1, respectively. The conversion between products was quantitative and complete in less than 10 min. It was also noted that the counterions had a significant effect on the formation of the [Ag4L4] cage. When using AgPF6 (with M:L ¼ 1:1), [Ag3L2] was the favored product along with free ligand, while the [Ag4L4] species was only observed in trace amounts. The triflate anion, however, templates the formation of the [Ag4L4] structure. Later, the same authors reported a tris-monodentate ligand based on a hexaphenylbenzene core.6 The disk-shaped ligand formed capsule-shaped [Ag4L4] or cage-shaped [Ag6L4] complexes depending on the relative concentration of AgI. The capsule-shaped [Ag4L4] species was obtained using a metal-to-ligand ratio of 1:1, and cage-shaped [Ag6L4] was obtained at a 1.5:1 ratio. Interconversion between the two assemblies was reversible. The capsule complex showed a binding affinity for the neutral adamantane molecule. The capsule-to-cage conversion resulted in the release of the encapsulated guest molecule. Using the same hexaphenylbenzene-based tris-monodentate ligand, Shionoya et al. reported that mixing the disk shaped ligand with 1.5 equivalents of Hg2 þ ions quantitatively formed a [Hg6L14] cage complex (Fig. 1).7 However, this self-assembled product was also dependent on the metal:ligand ratio, as using 0.75 equivalents of Hg2 þ ions resulted in the formation of a [Hg6L18] capsule. Interestingly, the size of both complexes is quite similar, as diffusion-ordered spectroscopy (DOSY) experiments measured the diffusion coefficients of 3.9  10 10 m2 s 1 and 3.7  10 10 m2 s 1 for [Hg6L14] and [Hg6L18], respectively. Tight packing of the [Hg6L18] capsule was evident as the 1H NMR signals of the p-tolyl protons belonging to the shorter ligand arms were shifted significantly upfield relative to the situation in the free ligand, due to shielding from neighboring aromatic ligands. Interconversion between the cage and capsule structures was possible in response to the ratio of ligand to Hg2 þ and conversion was complete within a few minutes. Structural conversion by alteration of the Hg2 þ ratio could be achieved by adding [2.2.2]-cryptand, a strong Hg2 þchelating reagent. Furthermore, the structural switching caused a remarkable change in the fluorescent properties of the selfassembled structures. Irradiation of the [Hg6L18] capsule in CH3CN with 284 nm light resulted in an emission at 360 nm, whereas the [Hg6L14] cage exhibited almost no fluorescence. Thus, reversible ON/OFF switching of fluorescence between the [Hg6L18] capsule and [Hg6L14] cage was achieved. The authors surmise that the changes in coordination geometry of Hg2 þ also change the contribution of the heavy atom effect, as the structural switching causes the a change from octahedral six-coordinate geometry of [Hg6L18] (including bound counter anions) to a linear two-coordinate geometry in [Hg6L14].

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Figure 1 Schematic representation of the quantitative and reversible structural interconversion between a fluorescent [Hg6L18] capsule complex and a nonfluorescent [Hg6L14] cage complex formed from tris-monodentate ligands L1 and Hg2 þ ions. Reprinted with permission from Harano, K.; Hiraoka, S.; Shionoya, M., J. Am. Chem. Soc. 2007, 129 (17), 5300–5301. Copyright 2007 American Chemical Society.

In 2014, the group of Yoshizawa reported a system consisting of HgII hinges and bent bispyridine ligands that could be transformed between an [M2L24] coordination capsule and an [M2L22] coordination tube (Fig. 2).8 These two structures were selectively formed depending on the ratio of metal and ligand. Switching between the capsule and tube was quantitative and reversible, complete within 15 min at room temperature. The [M2L24] species was characterized extensively by NMR spectroscopy. A significant upfield shift (Dd ¼ 1.01 and 0.84 ppm) of two protons was observed in the 1H NMR spectrum; these signals belonging to the two protons directed toward the center of the cavity and thus experience shielding from the aromatic anthracene panels. DOSY

Figure 2 (A) Selective formation of [M2L24] capsule and [M2L22] upon mixing of Hg(OTf)2 and ligand in CD3CN at room temperature and (B) formation and switching between [M2L24] coordination capsule and [M2L22] coordination tube. Reprinted with permission from Kishi, N.; Akita, M.; Yoshizawa, M., Angew. Chem. Int. Ed. 2014, 53 (14), 3604–3607.

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performed on the discrete assemblies gave a diameter of 1.6 nm for the capsule. The [M2L22] tube was formed using a 1:1 metal:ligand ratio and single crystal X-ray structure analysis showed a linear N–Hg–N arrangement. Both species contain cavities as a result of their composition, and although they are of similar diameter ( 1 nm), they exhibit markedly different host–guest chemistry. In this regard, the capsule is well suited to play host to the large spherical guests C60 and C70. The addition of further amounts of the metal ion induces capsule-to-tube transformation, and as the tubes had no affinity for these guests, they were subsequently released. Interestingly, a similar system using AgI metal ions and anthracene ligands also formed capsule and tube products, although this system was less sensitive to the metal:ligand ratio and displayed no switching capacity.9 In 2012, Fujita reported that heating a tris-pyridyl ligand with 0.5 equivalents of PdII resulted in the self-assembly of a single highly symmetric species, identified as an [M12L324] cuboctahedron (Fig. 3).10 The [M12L324] cuboctahedron structure contained noncoordinating pendant pyridyl groups, which could subsequently bind with an additional metal center to form an [M18L324] cuboctahedron derivative. Formation of this unique “stellated polyhedron” involved a process of closing the pendant pyridyl “gates” of the [M12L324] species. The reversible opening and closing of these gates was shown by the addition and chelate ligand-mediated sequestration of PdII ions. Chand et al. demonstrated a tris-monodentate ligand in combination with 0.5 equivalents of PdII gave a “spiro-type” [PdL42] macrocycle, exclusively (Fig. 4).11 In contrast, mixing the ligands with 0.75 equivalents of PdII resulted in a quadruple-stranded [Pd3L44] cage. The [Pd3L44] cage architecture contains two cavities that could each accommodate a small anionic guest such as fluoride, chloride, or bromide, however no encapsulation of iodide was observed. As with the previously discussed examples, the two complexes were interconvertible by varying the relative concentrations of ligand and PdII cations.

6.13.2.2

Solvent Responsive Systems

In 2007, a pair of solvent responsive cages was reported by Fujita et al. who showed the dynamic self-assembly of 1,2-bis[2-(pyridin4-yl)ethynyl]benzene ligands and PdII into box-shaped [Pd4L58] and triangular [Pd3L56] structures (Fig. 5).12 Controlling the equilibrium between the two assemblies was possible, and interconversion was modulated simply by changing the solvent. Using DMSO as the solvent, NMR, mass spectrometry and single crystal X-ray diffraction studies identified the self-assembly product as a [Pd4L58] species. However, when mixing the ligand and metal in the same stoichiometry but using MeCN as the solvent, quantitative formation of a [Pd3L56] assembly was observed. The addition of MeCN to a DMSO solution of [Pd4L58] altered the equilibrium, and increasing the ratio of MeCN lead to the corresponding decrease of the [Pd4L58] concentration and increase of the fraction of the [Pd3L56] structure in the mixture. This transformation was reversible as evaporation of MeCN resulted in the complete reformation of the [Pd4L58] assembly. The authors attributed entropic effects as the reason the equilibrium favored the [Pd3L56] structure in MeCN, whereas the favorable enthalpic win for [Pd4L58] in DMSO seems to overcompensate entropic effects. This was supported by evidence in the crystal structure where two molecules of DMSO and two nitrate ions were encapsulated in the cavity. Indeed, the importance of NO3  counterions in the formation of [Pd4L58] was confirmed as when Pd(OTf)2 was used in DMSO, a mixture of the two products was observed. Furthermore, dilution of the [Pd4L58] DMSO solution with other solvents also elicited transformation to the [Pd3L56] cage. In 2008, Aida et al. reported that alkynylene-bridged bis-porphyrin ligands with pyridyl donors form cyclic tetrameric cages upon mixing with ZnII cations.13 The ligands with longer alkynylene bridges were found to exist as a mixture of two conformationally isomeric tetramers. When using CCl4 as the solvent the zinc-porphyrin rings of each ligand favor a coplanar/parallel arrangement, whereas in benzene the ligands twist such that the Zn-porphyrin rings are perpendicular to each other. Using other solvents, the equilibrium between the two systems could be tuned. The conformation differences in the cages also resulted in a change in the absorption spectra, and thus this phenomenon was termed “conformational” solvatochromism. Work by Severin et al. has described a ruthenium-based coordination cage that underwent a solvent-induced structural rearrangement between an octanuclear prismatic cage and a tetranuclear assembly (Fig. 6).14 Interestingly, the structural rearrangement was possible through the use of two closely related solvents, CHCl3 and CH2Cl2. The octanuclear prismatic cage was observed in chloroform, whereas the equilibrium favored a tetranuclear complex in dichloromethane. Analysis by single crystal X-ray diffraction

Figure 3 Self-assembly of [M12L324] cuboctahedron, and reversible conversion between the [M12L324] cuboctahedron and the “stellated” [M18L324] cuboctahedron. Reprinted with permission from Sun, Q.-F.; Sato, S.; Fujita, M., Nat. Chem. 2012, 4 (4), 330–333.

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Figure 4 Assembly and interconversion of the “spiro-type” [PdL42] macrocycle and quadruple-stranded [Pd3L44] cage. Reprinted with permission from Bandi, S.; Pal, A. K.; Hanan, G. S.; Chand, D. K., Chem. Eur. J. 2014, 20 (41), 13122–13126.

Figure 5 Solvent-controlled assembly and interconversion of [Pd4L58] and [Pd3L56] structures. Reprinted with permission from Suzuki, K.; Kawano, M.; Fujita, M., Angew. Chem. Int. Ed. 2007, 46 (16), 2819–2822.

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Figure 6 Assembly of cage and solvent-induced rearrangement. Reprinted with permission from Kilbas, B.; Mirtschin, S.; Scopelliti, R.; Severin, K., Chem. Sci. 2012, 3 (3), 701–704.

and NMR spectroscopy provided evidence that hydrogen bonding of CH2Cl2 with the metallo-crown of the tetranuclear complex plays a major role in this process, with two CH2Cl2 molecules encapsulated within the cavities. These interactions were proposed to be the dominating stabilization factor of the octanuclear prismatic cage. Nitschke et al. have also reported a solvent responsive system.15 Subcomponent self-assembly of linear ligand precursors with an Fe(II) salt in water gave two architectures, an [Fe4L6] tetrahedron and an [Fe10L15] pentagonal prism. Addition of MeOH to the aqueous reaction mixture resulted in the preferential formation of the [Fe10L15] pentagonal prism. Recently in 2014, Hong and coworkers showed that the reaction of a tripodal tris-pyridyl ligand with AgBF4 in MeOH/CHCl3 (1:1) forms a transient [Ag6L4] cage.16 Interestingly, high concentrations of the monomeric cage led to polycatenated chains, whereas lower concentrations lead to head-to-tail electrostatic linking of the cages. Interestingly, using a strongly polar solvent such as DMSO resulted in disassembly of the polymeric and catenated structures to give discrete monomeric cages.

6.13.2.3 6.13.2.3.1

Guest-Induced and Template Driven Changes Structural transformations

The Raymond group reported an interesting example of a guest-induced transformation. The ligand was based on a 2,6diaminoanthracene backbone with bis(bidentate) catecholamide motifs and the self-assembled product was achieved using TiIV or GaIII metal ions.17 The unique geometry of the ligands allowed the formation of both an [M2L73] helicate and [M4L76] tetrahedron (Fig. 7). Formation of the [M2L73] triple helicate was found to be the entropically favored product. However, quantitative transformation of the [M2L73] species into an [M4L76] tetrahedron could be achieved by the addition of Me4NOH. A strong host–guest interaction of the anionic cage with the shape-complementary Me4Nþ cation was the driving force for the transformation, and resulted in the equilibrium shifted strongly towards formation of the [M4L76] tetrahedron.

Figure 7 Reaction of H4-L7 with [TiO(acac)2] or [Ga(acac)3] gives an [M2L73] helicate in the absence of Me4Nþ guest and an [M4L76] tetrahedron in the presence of Me4Nþ guest. The helicate can be converted into the tetrahedron simply by addition of Me4Nþ. Reprinted with permission from Scherer, M.; Caulder, D. L.; Johnson, D. W.; Raymond, K. N., Angew. Chem. Int. Ed. 1999, 38 (11), 1587–1592.

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Fujita et al. reported the larger guest molecule dibenzoyl templated an open cone [M8L4] assembly. Smaller carbon tetrabromide templated a tetrahedral coordination cage instead.18 In other work, Fujita also reported a ligand design consisting of a square panellike (3-pyridyl)-functionalized porphyrin.19 These ligands, in combination with [PdII(en)] (en ¼ ethylenediamine) hinge units, resulted in the formation of a [Pd6(en)6L3] porphyrin box structure with D3h symmetry. Pyrene was encapsulated within the host in 1:1 stoichiometry. NMR spectroscopy showed that the guest-binding event of pyrene resulted in the desymmetrization of the prismatic host, however the guest did not experience any desymmetrization. The 1H NMR spectrum of the desymmetrized host showed the twelve pyridyl rings were in six different environments, and likewise, the twelve pyrrole rings gave rise to six sets of signals. It was concluded that the guest binding caused the hosts to transform from D3h to C2 symmetry. The encapsulation of other guests was also reported. Host desymmetrization was only observed upon encapsulation of the large aromatic guest pyrene, perylene and triphenylene, while smaller guests such as benzene did not result in a conformational change. The authors proposed that guest binding of the larger species triggered flipping of two diagonal Py–Pd–Py hinges from the apical position to equatorial positions, thus changing the overall shape of the self-assembled cage. This proposal was also supported by computational studies. In 2006, Fujita et al. also reported a solvent dependent system as an aqueous solution of 1,4-bis(3-pyridyl)benzene ligand and cis-Pd(en)(NO3)2 afforded an [M2L82] compound (Fig. 8).20 The same reaction performed in DMSO gave an equilibrium mixture of [M2L82] and an [M3L83] triangle, which was found to be concentration dependent. Furthermore, at high concentrations an [M4L84] square macrocycle was observed. When using Pd(NO3)2 in DMSO, a 1:1 mixture of the [M3L83] macrocycle and tetrahedral [M4L88] cage was observed. However when Pd(TfO)2 was used, an [M3L86] double-walled triangle was obtained with only trace amounts of the tetrahedral [M4L88] cage. Interestingly, the use of either p-tosylate or BF4  counterions resulted in exclusive formation of the latter. The Nitschke group have used dynamic subcomponent self-assembly principles to create a large number of complex selfassembled systems. In 2011, Nitschke et al. introduced an [M4L6] tetrahedral metal-organic cage.21 Due to the dynamic nature of such ligands, the periphery of the ligands can be modified via exchanging the amine components that condense with aldehyde counter parts to form bidentate coordination sites. Interesting selectivity was observed in the nature of the cage periphery, with electron-rich amines being incorporated preferentially over electron-poor ones. Similar selectivity was observed on the cage interior, with PF6  being bound preferentially over TfO or BF4  . In another example from 2012, a [Co4L96] tetrahedral cage was formed through self-assembly of p-toluidine and 6,60 -diformyl-3,30 -bipyridine moieties. A dynamic library of host– guest systems was achieved when using suitable templating anions such as TfO or PF6  (Fig. 9).22 Furthermore, the addition of LiClO4 resulted in quantitative conversion to a [Co10L915] pentagonal prism. The larger NTf 2  , however, precluded the formation of the [Co10L915] pentagonal prism. Examination of this unprecedented transformation revealed that the perchlorate anions occupy the pockets of [Co10L915], being an ideal size and favored over the [Co4L96] precursor. Furthermore, the perchlorate anions possess a complementary geometry and are stabilized by four surrounding CoII cations. Another factor leading to the formation of [Co10L915] was found in the aromatic stacking of the electron-rich toluidine and electron-poor pyridine

Figure 8 1H NMR spectra of (A) L8, (B) NO3  templated [M4L88] tetrahedron, (C) BF4  templated [M4L88] tetrahedron, and (D) double-walled [M3L83] triangle (500 MHz, [D6]DMSO, 25 C), (A)–(E): double-walled edges, (A)0 –(E)0 : single-walled edges. Reprinted with permission from Chand, D. K.; Biradha, K.; Kawano, M.; Sakamoto, S.; Yamaguchi, K.; Fujita, M., Chem. Asian J. 2006, 1 (1–2), 82–90.

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Figure 9 (i) mixture of structures from subcomponent self-assembly from Co(NTf2)2 (ii) direct formation of the [Co4L96] tetrahedron by triflate templation (iii) formation of the [Co4L96] tetrahedron by addition of triflate or hexafluorophosphate anions to dynamic library (iv) the addition of LiClO4, resulted in quantitative conversion to a [Co10L915] pentagonal prism. Reprinted with permission from Riddell, I. A.; Smulders, M. M. J.; Clegg, J. K.; Hristova, Y. R.; Breiner, B.; Thoburn, J. D.; Nitschke, J. R., Nat. Chem. 2012, 4 (9), 751–756.

groups, resulting in a more compact structure. A further observation was that a chloride anion was strongly bound in the central pocket of [Co10L915]. An array of ten CH/Cl hydrogen bonding interactions was observed in the single crystal X  ray structure, and a number of other small anions (F, Br, N 3 , OCN , and SCN ) were also found to bind in the central cavity. The preparation of chloride free cage was challenging, although using a modified ligand allowed the formation of a cage with an empty central cavity and showed that templating from the peripheral perchlorate was sufficient to form the pentagonal prism and the chloride did not play a vital role. Further studies were conducted on the same rigid ligand in order to investigate the effects of both metal and anion templation on the assembly process.23 Self-assembly of the ligand with a range of metal cations (FeII, NiII, CoII, ZnII) and anions (NO3  , BF4  , ClO4  , TfO, NTf 2  ) was studied. The outcomes varied, obtaining discrete and polymeric metal-organic complexes, some of which were not intuitively based on geometric considerations. For FeII, the BF4  and ClO4  complexes initially formed tetrahedral cages, but upon heating were slowly converted to [Fe10L15] pentagonal prisms. However, when using TfO or NTf 2  counterions, the tetrahedral cages were not converted to a new species. In addition to the previous studies on cobalt, a distorted cuboid [Co18L12] compound was also observed when using NO3  or BF4  . In the case of BF4  , both pentagonal [Co10L15] prism and [Co18L12] cuboid were formed, however, after isolation of [Co10L15], conversion between to the two structures was not observed, indicating they are both kinetically stable. Nickel also produced a range of structures including tetrahedral (TfO), pentagonal prismatic (ClO4  ) and cuboid (NO3  ) complexes. Similarly, zinc produced a range of structures including pentagonal prismatic (ClO4  ), cuboid (BF4  ) and extended circular helical (TfO) complexes. Similar systems were reported using CdII ions that resulted in the formation of a fascinating range of new supramolecular architectures capable of interconverting in the presence of different stimuli.24 Remarkably, the use of dynamic imine exchange, varying templates and pH caused changes between four assembly motifs, these being an [M2L3]4 þ triple helicate, an [M3L3]6 þ triangle, an [M4L]8 þ cryptate-like cage, and an [M12L18]24 þ hexagonal prism. Further work published in 2014 used different amine components in the assembly to produce anion-templated cages.25 The anionic templates gave rise to four distinct architectures, namely a [Cd2L3] helicate, a [Cd8L12] distorted cuboid, a [Cd10L15] pentagonal prism, and a [Cd12L18] hexagonal prism. The addition of more strongly bound anions was found to drive interconversion between the aforementioned architectures. Concentration dependence was observed in the equilibrium between the [Cd12L18] prism and the [Cd2L3] triple helicate, as higher concentrations favored the former. The [Cd10L15] pentagonal prism was formed with the hexafluoroarsenate anion template, and this proceeded through assembly of an intermediate [Cd12L18] prism. Furthermore, addition of FeII cations caused remarkable system changes depending

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on the anion template present; metal exchange in these systems promoted formation of either an [Fe4L6] tetrahedron or [Fe10L15] pentagonal prism, representing significant structural alteration. In 2013, another [Fe4L106] tetrahedral cage was prepared by the Nitschke group, synthesized from 4,40 -diaminobiphenyl, 2-formylpyridine, and FeII components (Fig. 10).26 When using Fe(NTf2)2 the 1H NMR spectrum of the cage was complex but 2D NMR experiments elucidated that the cage interconverts between three diastereomers. The equilibrium between diastereomers was independent of concentration and temperature. However the system synergistically adapts to the addition of anionic guests, thereby altering the composition of diastereomers. When other iron salts were employed with TfO, ClO4  , or PF6  anions, the mixture of diastereomers was still present. The same ratio of self-assembled structures was observed for TfO, although ClO4  and PF6  were leading to a different behavior. Interestingly, when using BF4  only a single diastereomer was evident. 1H-19F HOESY and single crystal X-ray structure analysis showed that BF4  , ClO4  , and PF6  were encapsulated inside the tetrahedral cage. Titration with NO3  , Cl, Br, and I also resulted in quantitative encapsulation of the respective anions and gave a single diastereomer. Ligand flexibility and/or rotation was found to facilitate optimal guest binding, as demonstrated by guest-dependent cavity size adaptation observed in the studies; BF4  and ClO4  anions were found to reside in cavities of 69 and 74 Å3, respectively, thus reflecting a difference in anion size. The Nitschke group also demonstrated external stimulus-based control over self-assembled ZnII complexes formed with a trigonal pyramidal ligand.27 A triangular [Zn3LA3] triple helicate assembly was transformed into a triangular [Zn3LB2] double helicate upon addition of 8-aminoquinoline, causing substitution of some subcomponents. The [Zn3LB2] assembly contained a cavity that was shown to encapsulate a range of small aromatic guests. In other recent work, the subcomponent assembly of [FeII4L6] cages containing NiII-porphyrin-based ligands and FeII metal nodes was reported.28 A fascinating transformation of the cage occurred when C60 or C70 were added, resulting in the formation of an [FeII3L4] host–guest complex. The rearrangement was proposed to maximize p–p interactions between the host porphyrin units and the encapsulated fullerene guest. The [FeII3L4] complex contains one FeII center coordinating only two bidentate pyridylimine ligands. Consequently, the replacement of the unsaturated FeII cation with a tetrahedral CuI gave a hetero-metallic [guest@CuIFeII2L4] complex.

Figure 10 (A) Formation of the [Fe4L106] tetrahedral cage and (B) schematic view of the X-ray crystal structure, (C) schematic representation of the three diastereomers. Reprinted with permission from Clegg, J. K.; Cremers, J.; Hogben, A. J.; Breiner, B.; Smulders, M. M. J.; Thoburn, J. D.; Nitschke, J. R., Chem. Sci. 2013, 4 (1), 68–76.

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Another noteworthy example reported by Li et al. in 2013 detailed the formation of neutral cubic NiII-imidazolate [Ni8L12X4] cages (where X ¼ Cl or Br).29 Synthesis of the cages proceeds via subcomponent self-assembly, with all species playing a key role in stabilizing the resulting architectures. Addition of methylamine was found to promote a transformation of the cubic cage to a larger [Ni14L24] rhombic dodecahedral cage.

6.13.2.3.2

Transformations between monomeric and dimeric cages

In 2008, Kuroda et al. reported an example of a [Pd4L118]8 þ interpenetrated dimeric cage.30 The ligand consisted of two 3-pyridylmethoxy moieties coupled to a benzophenone core. Treating ligand L11 with 0.5 equivalents of Pd(NO3)2 in DMSO at ambient temperature for 1 h resulted in the formation of the monomeric [Pd2L114]4 þ cage. However, heating the reaction mixture for 24 h at 80 C saw conversion of the monomeric species to a fourfold interlocked structure [Pd4L118]8 þ composed of two entangled [Pd2L114]4 þ subunits (Fig. 11A). The formation of both monomeric and dimeric species was supported by NMR spectroscopy, ESI mass spectrometry as well as X-ray crystallography. In the 1H NMR spectrum of the monomeric cage a significant downfield shift of most protons was observed compared to those of the ligand alone. The 1H NMR spectrum of the [Pd4L118]8 þ double cage was also characterized by downfield shifting of the proton signals, but was complicated as all protons were split into an additional set of signals in a 1:1 ratio (Fig. 11B). This splitting pattern is characteristic of interpenetrated double cages, which arises from the loss of symmetry due to the upper and lower parts of each ligand experiencing different local environments. It is interesting to note that some protons attributed to the benzophenone core exhibit a small upfield shift upon formation of the interpenetrated cage, a direct result of the adjacent monomeric subunits’ close proximity. Thermostability studies on the thermodynamically stable double-cage product demonstrated that disassembly into the monomeric components only proceeded gradually at

Figure 11 (A) Self-assembly of a ligand based on a benzophenone backbone L11 and a metal source M ¼ PdII mixed in a ratio of 2:1 into an interlocked double-cage [3NO3@Pd4L118]5 þ and control over monomerization or dimerization triggered by guest addition. (B) 1H NMR (500 MHz, 293 K, DMSO-d6) spectra of the ligand, the intermediate monomeric cage and the double cage. (C) X-ray structure of [Pd4L118]8 þ. The solvent and counter anions have been omitted for clarity. Reprinted with permission from Fukuda, M.; Sekiya, R.; Kuroda, R., Angew. Chem. Int. Ed. 2008, 47 (4), 706–710.

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elevated temperatures (> 363 K). Standing for 7 days at ambient temperature regenerated the interlocked cage species. Three internal pockets of approximately equal volume (62 Å3) were observed in the single crystal X-ray structure of the interpenetrated cage [Pd4L118]8 þ (Fig. 11C). Each of the three cavities can accommodate a small anionic guest species. In this case, these guests are one of the primary driving forces that induce dimerization by acting as auxiliary templates. More specifically, employing NO3  as the anionic guests shifts the equilibrium largely towards formation of interpenetrated species. In addition to the NO3  anion being a suitable size for the internal voids, stabilizing hydrogen bonds between the nitrate oxygens and some hydrogen atoms of the ligand benzophenone backbone also drives formation of the interpenetrated double cage. Interestingly, other anionic guest molecules such as BF4  , PF6  , and TfO shifted the equilibrium towards the monomeric cage (favorably in the case of BF4  , or completely for PF6  and TfO). This behavior was explained as the larger anions do not fit inside the pockets of the double cage, impeding the formation of favorable hydrogen bonding. To study the driving force behind the dimerization process, the independent binding of various anionic species with the monomeric cage was studied. These experiments showed that NO3  was bound the strongest, with contributions from both electrostatic interactions and also its Lewis basic character. The size of the anion is also a contributing factor towards cage stability. As the cavity volume of the monomeric cage (406 Å3) is relatively large compared to the anionic guests, the encapsulation of two anions is possible. Interestingly, the association constant of the second anion was significantly lower than the expected value. Electrostatic repulsion from the close proximity of the two encapsulated anions results in negative cooperativity. Competition experiments were also conducted, finding that the double-cage [3NO3@Pd4L118]5 þ was the predominant product that arose from mixtures containing NO3  , BF4  , PF6  , and TfO anions. It is interesting to note that mixing the ligand and metal ion initially leads to the formation of a monomeric cage as an intermediate species, before proceeding to form the double cage. Transformation of the initially produced monomeric cages into the dimeric cages was observed to follow second order kinetics. The authors postulate that collision of two monomeric cages was the rate determining step of dimerization, rather than the comparatively fast guest-binding process. Furthermore, switching from the dimeric to the monomeric cage species was induced by the addition of larger anionic species (Fig. 11A).31 For example, the addition of 2-naphthyl sulfonate (ONs) to a solution of the nitrate-templated double cage functions as a trigger causing a dimeric-to-monomeric cage transformation. This transformation process followed a pathway beginning with anion exchange of the NO3  anions in the two outer pockets with ONs anions, giving a [2ONs þ NO3@Pd4L118]5 þ double-cage intermediate before generating the [2ONs@Pd2L114]2 þ monomeric species. Although the equilibrium was shifted towards the monomeric cage, the transformation was not quantitative as an equilibrium was reached after 125h at 21 C that contained 29% of the [3NO3@Pd4L118]5 þ double cage, 59% of the [2ONs@Pd2L114]2 þ monomeric cage, and 12% of the [2ONs þ NO3@Pd4L118]5 þ complex. Furthermore, utilization of p-toluenesulfonate (OTs) as a guest molecule resulted in the facile separation of the two species, as the monomeric species precipitated from a DMSO solution after heating the [3NO3@Pd4L118]5 þ double cage with (n-Bu4N)OTs for 96 h at 60 C. In 2008, Fujita et al. reported a notable example of a triply interlocked coordination cage.32 The interlocked structure was prepared by combining trans-1,2-bis(4-pyridyl)ethene L12 pillars, triazine-based ligands L13, Pd(en)(NO3)2 and triphenylene as a template. After heating the mixture of components at 100 C for 3 h, the quantitative formation of an interlocked host–guest complex was realized, namely a [3G@Pd12(en)12L126L134]24 þ double cage (Fig. 12). Characterization of the complex by 1H NMR spectroscopy and single crystal X-ray structure analysis clearly supported formation of the interlocked structure. 1H NMR spectroscopy revealed the triphenylene template signals were split into two sets in a ratio of 2:1, indicating that two triphenylene

Figure 12 Self-assembly of ligands L12 and L13 with triphenylene into the triply interlocked double-cage [3G@Pd12(en)12L126L134]24 þ. Reprinted with permission from Sekiya, R.; Fukuda, M.; Kuroda, R., J. Am. Chem. Soc. 2012, 134 (26), 10987–10997. Copyright 2012 American Chemical Society.

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molecules occupy the outer pockets of the cage and one triphenylene is encapsulated in the inner pocket. It is worthy to note that the triphenylene template was an indispensable component required for the self-assembly of the triply interlocked double cage. Using the same reaction conditions except in the absence of the templating triphenylene, a monomeric octahedral cage [Pd6(en)6L134]12 þ and a square [Pd4(en)4L124]8 þ species were obtained rather than the interpenetrated structure. The use of a templating molecule was not limited to triphenylene as the interlocked double-cage could be attained using different aromatic templates including perylene, fluoranthene, and coronene. Intermolecular p–p stacking within the tightly packed structure, between the electron poor triazine moieties and electron rich template molecules, were presumed to be the driving force for the formation of the dimer cage. The authors also showed that cages built from elongated pillar molecules contained larger voids in the inner pocket that could accommodate two or even three templating molecules. In work by Clever et al., the structural influences on the dimerization process of [Pd2L4] cages were studied by systematic modification of ligands based on the tricyclic dibenzosuberone and structurally related backbones carrying pyridyl donors attached via alkynyl spacers. Derivatization of the dibenzosuberone-based ligand was accomplished using a variety of approaches. For example, substitution of the alkynyl linkers with 1,4-phenylene units gave rise to slightly longer ligands. Other modifications have included the fixation of pendant groups using meta-substituted pyridines. In all cases, these modifications did not hamper the dimerization of the cages. However, reduction of the inward pointing carbonyl group of the suberone core to a methylene group was demonstrated to prevent double-cage formation.33 The observation that the carbonyl group stimulates dimerization of the dibenzosuberonebased cages was postulated to arise from favorable interactions between the internal Pd(py)4-planes and the carbonyl oxygen lone pairs, and therefore stabilize the interpenetrated structure. Solvent effects have also been observed to influence the doublecage dimerization process, as the use of DMSO resulted in the formation of a monomeric cage rather than the double-cage species. In comparison to MeCN, the larger size of DMSO reduces the number of solvent molecules that can be encapsulated within the cavity of the monomeric cages. As the dimerization process would result in the expulsion of fewer DMSO molecules, it is believed this process would equate to an inconsequential entropic gain. In a comprehensive study on the factors affecting double-cage self-assembly, Clever and coworkers synthesized a series of structurally related ligands using a variety of different backbones, each displaying variation in the distance between to two pyridine N-donors. Fig. 13A presents a selection of ligands that have been studied, indicating the products obtained from

Figure 13 (A) Structures and lengths (N,N distances) of ligands L18–L20 and empirical results on the anionic templates (BF4  , Cl and Br) that are able to induce double-cage formation (R ¼ n-hexyl); (B) and (C) the affinity for the exchange of both BF4  anions in the outer two pockets with chloride (solid line) and bromide (dashed line) has been calculated as a function of the optimized [Pd(py)4]-X–[Pd(py)4] potential for all three mechanically coupled pockets and the ligand length for a series of hypothetical double cages with a general formula [BF4@Pd4L8]5 þ. Grey areas indicate a region with 1 kcal mol 1 deviation in the calculation from the minimum. The optimal ligand lengths for accommodating bromide in the outer pockets is larger than that for chloride, but the binding energy for chloride is always larger than that for bromide. Reprinted with permission from Frank, M.; Dieterich, J. M.; Freye, S.; Mata, R. A.; Clever, G. H., Dalton Trans. 2013, 42 (45), 15906–15910.

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metal-mediated self-assembly when using the templating anions of BF4  and halides Br/Cl. It can be seen that the anion occupying the central pocket plays an important templating role. For example, ligands L15 and L16 form monomeric cages when templated with BF4  , where the anion is situated inside the central void. However, the same ligands form double cages when a smaller halide anion template is employed. Interestingly, the behavior of both cages originates from two distinct factors. The N–N-distance of ligand L14 is 11.36 Å and is not long enough to facilitate double-cage formation in the presence of either BF4  or Cl counterions, invariably resulting in formation of the monomeric cage. The longer ligand L17 and similar phenothiazine-based ligands L18–L20 were all observed to form double cages when the correct templating anion was applied. The influence of ligand design on the binding selectivity of guest molecules was also investigated by Clever et al. Anion binding experiments found that the double-cage [3BF4@Pd4L178]5 þ strongly favored the uptake of chloride over bromide. The authors then set out to create systems that would reverse this discrimination and preferentially bind bromide anions. A series of ligands with elongated backbones were designed and synthesized, and the resulting double cages contained binding pockets of varying size (Fig. 13A). This design was expected to provide a cavity more complementary towards bromide anions. The binding selectivity between the two halides was examined using competitive titrations where bromide-containing double cages were treated with chloride anions and vice versa. However, these competition experiments found that cages with longer ligands and the corresponding larger cavity size did not result in the anticipated reversal of binding selectivity to favor bromide anions.34 Surprisingly, these experiments revealed that there was never a tendency for the selective binding of bromide anions, while chloride was strongly favored in the double-cage structure bearing smaller cavity sizes. Elongation of the ligands did not alter the binding preference, only decreasing the binding strength of both the chloride and bromide anions until a comparable level was reached. Computational methods were also considered and found to support the experimental results.35 The double-cage structure was truncated for computational considerations and calculations were implemented using three [Pd(py)4]-X–[Pd(py)4] fragments (Fig. 13B). Considerations concerning the mechanical coupling of the pockets were taken into account for the calculations as the anion triggers the double cage to compress along the Pd4-axis, resulting in the expansion of the inner pocket while the two outer pockets condense. The exchange of the BF4  with Cl or Br in the outer two pockets was calculated for ligand N–N distances ranging from 14 to 17 Å. Based on the aforementioned factors, the calculations affirmed that the optimized ligand length for the binding of larger bromide anions in the two outer pockets was significantly longer than for chloride (Fig. 13B). However, comparing the relative energies of each binding event showed that chloride binding is always energetically favored over bromide. The reason for this behavior was assumed to be connected to the higher charge density of the harder chloride as compared to the softer bromide, the former leading to a more pronounced Coulomb interaction with the adjacent palladium cations. Consequently, the binding of chloride is favored even for ligand lengths ideally suited to accommodate bromide. The plot of the systems’ energy shows that elongating the ligands reduces the preference of chloride binding over bromide until both are energetically indistinguishable. Examining these distances, ligands optimized for the binding of chloride were calculated to be relatively short (14.8 Å), while longer ligands were expected to have a weaker affinity for chloride. Experimental observations were in agreement with the calculations, demonstrating that cages incorporating longer ligands had a reduced affinity for chloride anions. Concerning modification of the anion binding selectivity in interpenetrated double cages, an alternative approach investigated whereby the templating anion occupied the central pocket was exchanged with that of a different size. With this in mind, a ligand appended with a bulky central moiety was prepared by a Grignard reaction on the suberone core (Fig. 14). Although ligands L17 and L16 were closely related, the propensity for dimerization and anion binding properties of the corresponding cages were profoundly different. Upon mixing with palladium tetrafluoroborate, the dibenzosuberone-based ligand L17 initially gave the [Pd2L174]4 þ monomeric species as a kinetic product, which subsequently dimerized to form the [3BF4@Pd4L178]5 þ double cage, carrying BF4  anions in all three pockets. Ligand L16, on the other hand, formed the monomeric cage exclusively, with no dimeric products observed even after heating for an extended period. The BF4  that would be situated in the central pocket of a double cage is sufficiently impeded by the bulky central substituents of the dibenzosuberone-based backbone. Incorporation of the relative large BF4  and the resulting deviation of the bulky substituents did not occur as the degree of repulsive forces would destabilize the overall double-cage structure. However, induction of the dimerization process was thought to be achievable using a small anion template such as chloride, because it would result in larger outer cavities in whose vicinity the sterically congested environments of the double cage reside. Indeed, the addition of 0.5 equivalents of (n-Bu4N)Cl to the monomeric cage [Pd2L164]4 þ effected the transformation and resulted in the new [2BF4 þ Cl@Pd4L168]5 þ double cage. Single crystal X-ray diffraction and NMR spectroscopic studies showed that a sole chloride anion occupied the central pocket, whereas disordered BF4  anions were observed in the two outer pockets of the double cage. A comparison of the crystal structures of the BF4  -templated dimer [3BF4@Pd4L178]5 þ and the chloride-templated double-cage [2BF4 þ Cl@Pd4L168]5 þ revealed that the inner Pd/Pd distance had decreased from 8.25 Å to 6.26 Å. This observation highlights the structural change induced by the smaller chloride anion. Similarly, the voids of the two outer pockets were expanded, clearly apparent as the distance between the outer palladium and its closest neighboring palladium center increased from 8.09 Å to 8.79 Å (Fig. 14). As a result, the selectivity of guest binding in the outer pockets was altered from small anionic molecules toward larger guests. The effect of enlarging the outer voids was evident in the uptake of larger anionic guests including perchlorate, hexafluorophosphate, and perrhenate. Notably, ReO4  bound in both outer pockets in a cooperative manner, with binding constants of K1 ¼ 2158 m 1 and K2 ¼ 1848 m 1, respectively. Calculations of the pocket volumes and the corresponding packing coefficients of the anions were also in agreement with these experimental findings.36 The outcome of the studies realized a number of parameters that are essential to consider for the assembly of interpenetrated double-cage systems from banana-shaped bis-monodentate ligands. The most important factors influencing the dimerization process were found to be the length, overall shape and steric factors of the ligands, the choice of the templating anion, as well

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Figure 14 Top: self-assembly of ligand L17 with PdII cations to give double-cage [3BF4@Pd4L178]5 þ via a monomeric cage intermediate. Addition of chloride to [3BF4@Pd4L178]5 þ results in the formation of the [2Cl þ BF4@Pd4L178]5 þ host–guest complex having a relatively large BF4  anion in the central pocket and small chlorides in the outer pockets. Bottom: ligand L16 carries extra steric bulk in the middle of the backbone. The sterically crowded situation does not allow for the double-cage formation using a larger BF4  template. Addition of chloride to the monomeric cage [Pd2L164]2 þ, however, results in the formation of interpenetrated dimers with a chloride anion in the central pocket. This [Cl@Pd4L168]7 þ cage featuring a small template in the central pocket is then able to incorporate bigger guests such as ReO4  in the two outer pockets. In the depicted crystal structures, the volumes of the outer pockets were calculated by the VOIDOO software. Reprinted with permission from Freye, S.; Michel, R.; Stalke, D.; Pawliczek, M.; Frauendorf, H.; Clever, G. H., J. Am. Chem. Soc. 2013, 135 (23), 8476–8479. Copyright 2013 American Chemical Society.

as the solvent and metal (i.e., PdII instead of PtII). It is noteworthy that very short ligands such as L14 do not form double cages under any circumstances. It was even shown that small monomeric cages can concurrently exist in the presence of double cages assembled from longer homologues. Social self-sorting can be observed when ligands of significantly different lengths are mixed with Pd(II) cations, although ligands of complementary size and shape have a tendency to afford statistical distributions of mixed-ligand cages when reacted under the same conditions.37

6.13.2.3.3

Halide-responsive allosteric processes in interpenetrated cages

Besides the abovementioned effects concerning cage dimerization, Clever et al. also showed that certain double cages show internal structural changes with implications for subsequent guest-binding events in response to the uptake of the first (and second) anion. The first double cage in this group featured the already mentioned bis-monodentate pyridyl ligands L17 based on a dibenzosuberone backbone (Fig. 15A).38 This ligand has a lower structural flexibility, compared to the ligand reported by Kuroda et al.,30,31 and the cage bears endohedrally oriented carbonyl groups. The double cage contains three pockets that each incorporates a BF4  anion. In this case, BF4  did not affect the dimer formation negatively, in contrast to Kuroda’s system where the use of BF4  counterions prevented quantitative dimerization. The [3BF4@Pd4L178]5 þ structure obtained from single crystal X-ray diffraction was analyzed, and the volume of the central and each outer pocket was calculated to be approximately 108.9 and 49.9 Å3, respectively. As these internal cavities were relatively small, the uptake of small anionic guests (i.e., halides) was investigated. Substantial shifting of some signals in the 1H NMR spectrum occurred upon the addition of one equivalent of (n-Bu4N)Cl per double cage, corresponding to the formation of a [2Cl þ BF4@Pd4L178]5 þ species. Interestingly, only half of the [3BF4@Pd4L178]5 þ species was transformed to the corresponding [2Cl þ BF4@Pd4L178]5 þ double cage following the addition of one equivalent of chloride. As no intermediate species containing a single halide anion was observed by 1H NMR spectroscopy or mass spectrometry, it was evident that the uptake of two chloride anions in each double cage operated via a strong cooperative binding process. Furthermore, exchange of BF4  with the smaller Cl anions induced a contraction along the Pd4-axis of the double cage. The distance between the two outer palladium atoms reduced from 24.4 Å in the [3BF4@Pd4L178]5 þ species to 23.6 Å in the [2Cl þ BF4@Pd4L178]5 þ species (Fig. 15B). These observations gave support to an allosteric binding mechanism in this interpenetrated system. Binding of the first chloride and the resulting cage-compression are proposed to preorganize the second binding site in a positively cooperative allosteric manner, tremendously enhancing the binding affinity of the second halide anion. Further analysis of the double-cage structure revealed that in addition to a 3.3% compression of the double cage along the Pd4axis, the binding of chloride also triggers a helical torsion of 8 degrees in each of the monomeric subunits. The use of DOSY also evidenced halide-induced contraction of the double cage. The inter-ligand distances of the double cage were measured using NOESY experiments, which enabled the amount of helical twisting to be determined. Furthermore, analysis of molecular models incorporating DOSY and NOESY experimental data determined the volume of the two outer cavities in [2Cl þ BF4@Pd4L178]5 þ was

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Figure 15 (A) Self-assembly of dibenzosuberone-based ligand L17 with a PdII source in a 2:1 ratio into an interlocked double-cage [Pd4L178] and temperature dependence of anion exchange processes. At low temperatures, a slow exchange of the BF4  occupying the outer pockets is observable. Upon increasing the temperature, the exchange rate for these BF4  anions increases, whereas the BF4  anion inside the central pocket stays locked. Addition of (n-Bu4N)Cl results in positive allosteric binding of two halide anions into the two outer pockets. (B) Comparison of the crystal structure of [3BF4@Pd4L178]5 þ with a DFT calculated structure of [2Cl þ BF4@Pd4L178]5 þ based on NOESY distance measurements showing a decrease in the Pdouter–Pdouter distance upon uptake of chloride anions in the two outer pockets. (C) 1H NMR spectral monitoring of the addition of solid AgCl to [3BF4@Pd4L178] in acetonitrile after 5, 10, and 15 min of vigorous stirring. Reprinted with permission from Freye, S.; Engelhard, D. M.; John, M.; Clever, G. H., Chem. Eur. J. 2013, 19 (6), 2114–2121.

decreased by 53%, while that of the inner pocket was increased by 43% relative to the single crystal X-ray structure of [3BF4@Pd4L178]5 þ. 19F NMR spectroscopy revealed the BF4  anion occupied the central pocket remained locked in position and therefore did not undergo exchange with other anions in solution. Interestingly, 19F NMR relaxation experiments could be successfully employed to monitor mobility differences of the BF4  anion within the central cavity before and after its halidetriggered expansion. In comparison, exchange of the BF4  anions that occupy the outer pockets was observed, although the exchange rate was largely influenced by solvent and temperature. As expected, the anion exchange rates were accelerated with both elevated temperatures and increasing solvent polarity (Fig. 15A). The observed halide binding preference, ordered from strongest to weakest, was chloride > bromide > fluoride (see previous section for a more detailed study of the chloride versus bromide binding). In the presence of the larger iodide anions, the cage was observed to partially disassemble, presumably due to coordination of the halide with the palladium cations and substitution of pyridyl ligands. It should be noted that in all cases, competitive coordination conditions with excess halide anions led to decomposition of the coordination assemblies. On the other hand, the affinity of the outer pockets was found to be much higher for the binding of halide anions than the direct coordination to the square-planar palladium centers. Consequently, pyridyl replacement was only observed in the presence of larger amounts of halides, long after the outer pockets had already been saturated. Extraction of halides by AgI back-titration experiments was performed to determine the net association constant of two chloride anions that bind inside the two outer cavities of [BF4@Pd4L178]7 þ, finding an extremely high value of approximately Knet ¼ 1020 M 2. The binding of chloride with the double cage was so strong that the highly insoluble AgCl in MeCN was dissolved (Fig. 15C). In contrast, larger anions such as PF6  were not encapsulated in the double-cage assembly and no significant effects were observed with respect to cage stability.38,39 Additional studies on anion binding and the role of templating molecules saw the development of another ligand that was found to give interpenetrated double cages. The acridone-based ligand L21 assembled into an interpenetrated dimer [3BF4@Pd4L218]5 þ when reacted with palladium tetrafluoroborate and subsequently into [2Cl þ BF4@Pd4L218]5 þ in the presence of two equivalents of halide anions (Fig. 16A).40 Crystals of [3BF4@Pd4L218]5 þ were grown by diffusion of benzene into an acetonitrile solution. Single crystal X-ray structure analysis revealed that the [3BF4@Pd4L218]5 þ double cage cocrystallized with benzene, which were observed to reside in the channels of the crystal lattice in-between the discrete cage structures. Surprisingly, the X-ray structure of the analogous chloride-containing double cage was found to contain one benzene molecule in place of the BF4  anion that previously occupied the central pocket. Encapsulation of a neutral benzene molecule to form the [2Cl þ benzene@Pd4L218]6 þ assembly meant the overall charge changed from a penta-cationic to a hexa-cationic species.

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Figure 16 (A) Assembly and anion binding of cage [3BF4@Pd4L218]5 þ, followed by uptake of neutral guest molecules into the halide activated species. (B) X-ray structures of [3BF4@Pd4L218]5 þ and [2Cl þ benzene@Pd4L218]6 þ. The benzene molecules are drawn in black. (C) Comparison of uptake kinetics and thermodynamics with different neutral guests and different halides. Reprinted with permission from Löffler, S.; Lübben, J.; Krause, L.; Stalke, D.; Dittrich, B.; Clever, G. H., J. Am. Chem. Soc. 2015, 137 (3), 1060–1063. Copyright 2015 American Chemical Society.

This remarkable halide-triggered transformation whereby the central BF4  anion is exchanged for a neutral molecule was also examined in solution. Fascinatingly, a variety of small neutral molecules, including cyclohexane, toluene, and norbornadiene, were found to be encapsulated inside the central pocket of the halide-activated double cage. Further experiments were performed on the chloride-activated double cage to investigate the kinetics and binding strength for benzene and cyclohexane. Additionally, the encapsulation kinetics of norbornadiene was investigated and compared between bromide and chlorideactivated cages (Fig. 16C). Interestingly, the double-cage [2Br þ BF4@Pd4L218]5 þ can be rapidly restored back to the [3BF4@Pd4L218]5 þ species via the titration with AgI cations, whereas the double cage accommodating a neutral molecule is kinetically hindered and remains unaffected by the addition of AgI unless the sample is heated or stored for longer times (Fig. 16A).

6.13.2.4

Action of Competitive Ligands

Crowley et al. have reported some stimuli-responsive [Pd2L4] cages that have pyridine units pointing toward the cavity centroid.41 This new assembly was shown to encapsulate two molecules of the anticancer drug cisplatin, all of which is mediated by concerted host–guest hydrogen bonding interactions. The single crystal X-ray structure of the [(cisplatin)2@Pd2L4] complex was determined, and the whole assembly was found to be unstable toward the introduction of a competing ligand. Although this was the case, addition of 8.0 equivalents of DMAP had the effect of triggering release of the endo-cavity cisplatin guest molecules. Subsequent reassembly of the cage was achieved by the addition of TsOH or (þ)-camphor-10-sulfonic acid, through selective protonation of the DMAP ligands. The same disassembly/reassembly process of the cage was achieved using chloride (8.0 equivalents of n-Bu4NCl) and AgSF6 as chloride scavenger, respectively. In 2015, Crowley et al. reported a followup study that demonstrated chloride-driven transformation of a metallosupramolecular [Pd2L4]4 þ cage to a [Pd2L2Cl4] metallo-macrocycle. Regeneration of the [Pd2L4]4 þ cage was achieved by treatment of the [Pd2L2Cl4] macrocycle with AgBF4. The process was reversible, and additionally, encapsulated molecules in the cavity of the [Pd2L4]4 þ cage could be released by chloride-triggered cage disassembly.42 The same disassembly and reassembly approach discussed earlier using DMAP and TsOH was also utilized by Hardie et al., where they could control the self-assembly of a [Pd6L8] cage using tripodal ligands based on a cyclotricatechylene core.43

Structural Transformations in Coordination Cages

6.13.2.4.1

347

Halide-triggered structural reorganization

During the course of studying halide encapsulation in double cages, Clever et al. prepared ligand L15, based on a carbazole backbone and designed to be of intermediate-length relative to the previously examined ligands. Size considerations and molecular modeling results obtained from previous studies were taken into account in the ligand design, and it was expected to assemble into monomeric cages when using BF4  counterions rather than forming double cages. Indeed, mixing the ligand with [Pd(CH3CN)4](BF4)2 afforded a stable [Pd2L154]4 þ monomeric cage as the sole product (Fig. 17A).44 Analysis of the structure obtained from single-crystal X-ray diffraction revealed the monomeric cage [Pd2L154]4 þ had a relatively short Pd–Pd distance of 14.31 Å (Fig. 17B). Next, the effect of halide addition was examined. Since previous studies on anion binding in various cage derivatives revealed that the optimal Pd–Pd distance for the binding of halide anions in a sandwich mode lies between 6.5 and 7.5 Å, just half of the distance found in monomeric cage [Pd2L154]4 þ, halide-triggered dimerization was assumed to be possible with this ligand. Indeed, NMR and mass spectrometry results confirmed that the addition of 1.5 equivalents of bromide or chloride to the monomeric cage initiated transformation to an interpenetrated double-cage [3X@Pd4L158]5 þ (X ¼ Cl or Br), where each pocket is filled with a halide. A DFT model (uB97XD/def2-SVP) of the [3Cl@Pd4L158]5 þ double cage was calculated as no crystal structure was attained (Fig. 17C). The palladium–palladium distances measured from the calculated structure were significantly shorter than those previously observed in double cages (Pdouter–Pdinner of 6.58 Å and Pdinner– Pdinner of 7.02 Å). The relatively short distances were reflected in the limited capacity of the cavity, which could only accommodate small anionic guests and therefore effect dimerization. Formation of the dimeric structure was observed, although it was only one component of an equilibrium mixture consisting of the monomeric cage, dimeric cage, and noncoordinated ligand in a ratio of 5:2:10 and 5:5:2 with bromide and chloride, respectively. The addition of excess halide anions did not shift the equilibrium toward the double cage but rather increased the ratio of the free ligand present, arising from the competitive metal coordination between the pyridine ligands and halides. Crystals were obtained from the equilibrium mixture containing a slight excess of bromide anions, and fortuitously a {trans-[(PdBr2)2L152]}3 triply-catenated product was discovered. The catenane is an unusual topology that not been observed in any of the previously described examples, and has the unique feature of being neutrally charged as the PdII cations, each coordinates two halide anions. The neutrally charged PdBr2(pyridine)2 moieties permit the metal atoms to reside in immediate proximity to each other, as opposed to the double cages where anions are situated inbetween each metal node. Consequently, the Pd–Pd distances in this triple catenane are much shorter, ranging from 4.08 to 4.78 Å (Fig. 17D). The six palladium atoms of the double cage were approximately linearly arranged, whereas the bromide substituents were observed to follow a helical pattern. The topology of this mechanically interlocked species seems to be related to Borromean rings, which consist of three linked rings where removal of any single ring also unlocks the remaining two rings. However, the triply catenated [(PdX2)6L156] species differs as all rings are mechanically interlocked with each other and breaking one ring leaves the two remaining rings linked.44

Figure 17 (A) Self-assembly of a carbazole-based ligand L15 with PdII into the monomeric cage [Pd2L154]4 þ, followed by halide-triggered formation of the double-cage [3X@Pd4L158]5 þ and conversion into the neutral triple-catenane [(PdX2)6L156]0 upon addition of larger amounts of halide anions. (B) X-ray structure of the monomeric cage [Pd2L154]4 þ, (C) DFT calculated structure for the double-cage [3Cl@Pd4L158]5 þ and (D) X-ray structure of the triple-catenane [(PdBr2)6L156]0. Reprinted with permission from Zhu, R.; Lübben, J.; Dittrich, B.; Clever, G. H., Angew. Chem. Int. Ed. 2015, 54 (9), 2796–2800.

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Figure 18 Formation of TiIV and heteronuclear PdII-TiIV complexes. Reprinted with permission from Hiraoka, S.; Sakata, Y.; Shionoya, M., J. Am. Chem. Soc. 2008, 130 (31), 10058–10059. Copyright 2008 American Chemical Society.

6.13.2.5

pH-Induced Changes

In 2008, Shionoya reported a switchable self-assembled system, where the transformation process was stimulated by the addition of acid and base, respectively (Fig. 18). The mixed metal TiIV and PdII-based ring assembly was shown to convert into a [Pd3Ti2L226Cl6]4  cage by modifying the basicity of the solution. The interconversion process was reversible by switching between TFA and n-Bu4NOH, although the transformation also required the addition of the respective ligand and metal.3a Lusby and coworkers demonstrated the stimuli-responsive assembly and disassembly of ring and cage-like architectures.45 Treating a dinuclear platinum complex with either ditopic or tritopic pyridyl donor ligands resulted in the formation of a molecular square or a trigonal prism, respectively. Both assemblies could be disassembled by treatment with base, as the platinum complex can interconvert between coordination modes. Reversible assembly and disassembly of the prism was demonstrated by the addition of either acid or base as required.

6.13.3

Redox-Induced Changes

In other work, Clever et al. have also investigated the use of ligands with integrated redox-active character.46 The well-studied redoxactive phenothiazine moiety was chosen as the ligand core, due to the possibility of both one- and two-electron oxidation reactions. The capacity for this chemistry makes phenothiazine a popular choice as an electron-donor when studying photoinduced charge separation. Heating the ligand with 0.5 equivalents of [Pd(CH3CN)4](BF4)2 at 70 C for 6 h resulted in the formation of an interpenetrated double-cage [3BF4@Pd4L208]5 þ. Quantitative formation of the double cage was monitored via 1H NMR spectroscopy and high-resolution ESI mass spectrometry. Exploiting the redox-active character of the phenothiazine moiety, ligand L20 was reacted in a two-electron oxidation using Cu(NO3)2 $ 3H2O as a mild oxidizing agent. Applying the oxygenation reaction conditions to ligand L20 produced the mono-S-oxygenated ligand L18, which subsequently self-assembled to form the corresponding [3BF4@Pd4L188]5 þ double cage when mixed with PdII (Fig. 19). The 1H NMR signals of the oxygenated double cage were very broad, which was not unexpected as the ligand’s sulfoxide oxygen can conform to a pseudo-equatorial or a pseudo-axial orientation. Nevertheless, the double cage has been clearly identified by ESI mass spectrometry. Employing harsher reaction conditions, whereby ligand L20 was treated with meta-chloroperoxybenzoic acid (m-CPBA), afforded a ligand with a di-S-oxygenated phenothiazine core and N-oxygenated pyridine arms. To obtain the desired ligand L19, the undesired pyridine-N-oxide groups were reduced to the corresponding pyridines by treatment with iron powder in acetic acid (Fig. 19A). As seen with the previous examples, ligand L19 also formed interpenetrated double cages. Single crystal X-ray structures were obtained for all three double cages with varying degrees of oxygenation.34,37,46 While all three dimeric assemblies presented identical topologies, each structure could be easily identified based on their differing Pd–Pd distances. It was also apparent that the endohedrally oriented oxygen substituents imparted subtle steric

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Figure 19 (A) Self-assembly of redox-active cages based on phenothiazine-based ligand L20 to give the interlocked double-cage [Pd4L208]8 þ. Oxidation of L20 by (i) copper nitrate in CH2Cl2 affords a mono-S-oxygenated ligand L18 which assembles to the corresponding double-cage [Pd4L188]8 þ. Harsher oxidation conditions using (ii) m-CPBA in CH2Cl2 followed by (iii) iron in acetic acid delivered di-S-oxygenated ligand L19 which forms double-cage [Pd4L198]8 þ. The X-ray structures of all three cages are shown in comparison under omission of the anions in the pockets. (B) Space filling top-view on the central [Pd(pyridine)4] complex extracted from the crystal structure of all three double cages showing the distances between the palladium and sulfur atoms. (C) Partial overlay of substructures of [Pd4L208]8 þ (grey), [Pd4L188]8 þ (red) and [Pd4L198]8 þ (blue) indicating the changes in the ligand bend and the Pd–Pd distances. Reprinted with permission from Frank, M.; Hey, J.; Balcioglu, I.; Chen, Y.-S.; Stalke, D.; Suenobu, T.; Fukuzumi, S.; Frauendorf, H.; Clever, G. H., Angew. Chem. Int. Ed. 2013, 52 (38), 10102–10106. Copyright 2013 American Chemical Society.

influences that resulted in a slight twist around the Pd4-axis (Fig. 19B). Similarly, the extent of oxygenation determined the amount of bending in the ligand core (Fig. 19C). It was expected that the confined environment of the eight ligands within the compact interpenetrated system would permit electronic communication among the individual ligands and thus alter the redox properties of the double cage. Therefore, the redox chemistry of the double cages was investigated. The authors showed that chemical or electrochemical oxidation of [3BF4@Pd4L208]5 þ in anhydrous conditions produced an eightfold radical-cationic species. This reacted in the presence of water to yield a double-cage product containing ligands that were mono-S-oxygenated. Isotopically labeled H18 2 O confirmed that water was indeed the source of the newly incorporated oxygen substituents. A radical disproportionation reaction was proposed to occur as the oxygenation kinetics of the double cage deviated from that of the ligand alone. Applying the oxygenation conditions to the free ligand generated the corresponding radical cation species, which reacted with water at a slower rate compared to that of the eightfold radical-cationic dimeric cage. It was postulated that the tight packing in the interpenetrated dimeric cage raises the probability that a disproportionation reaction occurs, compared to the slower reaction rate of the free ligand arising from a bimolecular process.46 Further work by Clever et al. reported mixed-ligand cages containing electron-rich phenothiazine and electron-poor anthraquinone ligands. In contrast to mixtures of the pure donor/acceptor double cages, only these mixed-ligand species show light-induced charge transfer within the densely packed double-cage framework, as evidenced by time-resolved femtosecond UV–vis spectroscopy.47 Sallé and coworkers have used pyridine-functionalized bis(pyrrolo)tetrathiafulvalene ligands to generate electroactive coordination cages. The self-assembly reaction was performed using a cis-(PEt3)2Pt(OTf)2 complex in DMSO at 75 C for 2 h, resulting in the quantitative formation of a cis-[(PEt3)2Pt6L3] trigonal prism.48a Recently, the same group reported an example of a redox-triggered

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Figure 20 Assembly of the [Pd4(dppf)4L232] cage, and schematic illustrating the redox-controlled cage disassembly/reassembly process. Reprinted with permission from Croué, V.; Goeb, S.; Szalóki, G.; Allain, M.; Sallé, M., Angew. Chem. Int. Ed. 2016, 55 (5), 1746–1750.

process from a coordination cage.48b The tetrapyridyl ligands L23 were based on an extended tetrathiafulvalene (exTTF) core. Selfassembly of the [Pd4(dppf)4L232] cages was performed by mixing the ligand L23 with cis-Pd(dppf)(OTf)2 in acetonitrile at room temperature (dppf ¼ bis(diphenylphosphino)ferrocene) (Fig. 20). The authors also showed guest binding of neutral polyaromatic guests such as perylene, as well as the dodecafluorododecaborate anion [B12F12]2  forming a 1:2 host–guest complex. The electrochemistry of the cages was investigated thoroughly. The electron-rich exTTF unit can be readily oxidized to the exTTF2 þ dication. The exTTF unit favors a bent structure although oxidation to exTTF2 þ is accompanied with a significant conformational change to a flat aromatic system. The [Pd4(dppf)4L232] cage was shown to disassemble upon selective chemical oxidation with four equivalents of the thianthrenium radical cation. The planar geometry of the oxidized exTTF2 þ ligands and the electrostatic charge repulsion between exTTF2 þ and the Pd ions were both contributing factors in disintegrating the cage structure. Interestingly, subsequent reassembly of the cage was possible by reduction with two equivalents of tetrakis(dimethylamino)ethylene. The reversible nature of the disassembly/reassembly process of the redox-active cage was also demonstrated with the [B12F12]2 -containing host–guest complex, thereby realizing a redox-switchable uptake and release system for the anionic guest (compare to the photoswitchable host for the same guest discussed below). This unique example offers insight into new supramolecular approaches for controlled guest-delivery.

6.13.4

Light-Induced Changes

Light is an excellent stimulus the one can use to induce reversible structural changes in both molecular and supramolecular systems. Photoresponsive cages can be produced by the attachment of peripheral photoactive groups or by the integration of photoactive moieties into a ligand core. Examples of both approaches will be discussed in the following sections.

6.13.4.1

Switching of Guest Binding

Fujita et al. incorporated the well-known photoswitchable azobenzene moiety into boomerang-shaped ligands. The ligands selfassemble into a [Pd12L24] spherical complex that contains an array of 24 endohedral azobenzene units. Isomerization in the form of trans-to-cis switching of the inward-facing azobenzene groups was shown to alter the hydrophobicity of the cage’s cavity. This in turn modulated the binding of a 1-pyrenecarboxaldehyde guest.49 Zhou et al. have shown ligands based on isophthalic acid with an azobenzene unit attached.50 Mixing with CuII resulted in a “paddle-wheel”-type cuboctahedral cage [Cu24L24]. As the pendant azobenzene chromophores are on the exterior of the cage, and not within the cavity of the host as in Fujita’s example, the isomerization of these groups did not affect the host–guest chemistry of the cage’s cavity in solution. Interestingly, however, it was shown that guests bound in interstitial binding sites between aggregates of the poorly soluble trans-isomer cages, but upon irradiation with UV light and isomerization to the soluble cis form, the guests were released again into solution. The capture and release process upon cis/trans isomerization was reversible by alternation between blue and UV light. Clever reported a dithienylethene (DTE)-based cage that could be controlled by light to induce structural changes within the cage framework, as opposed to switching of an appended group.51 The resulting structural change in the cage architecture was also shown to modulate guest binding. The bis-monodentate ligand L24 is based on the photochromic DTE unit, which could be reversibly interconverted between an open- and closed-ring form by irradiation with UV or white light, respectively (Fig. 21A). The openring form of the ligand o-L24 is conformationally flexible as the pyridyl arms are connected to the perfluorinated core through single

Structural Transformations in Coordination Cages

351

Figure 21 (A) The conformationally flexible bis-monodentate pyridyl ligand o-L24 based on a dithienylethene (DTE) photoswitch is converted into its rigid closed-ring isomer c-L24 upon irradiation at 365 nm. The process can be fully reversed by irradiation with white light. (B) Addition of stoichiometric amounts of PdII leads to quantitative formation of coordination cages o-C ¼ [Pd2(o-L24)4](BF4)4 and c-C ¼ [Pd2(c-L24)4](BF4)4, which again can be interconverted by the described photochemical processes. (C) Both cage isomers can encapsulate the spherical guest G ¼ [B12F12]2 . Complex G@o-C is formed by the dynamic host o-C with much higher yield than G@c-C is formed from the rigid host c-C. Thus, irradiation of the host–guest complexes results in the reversible uptake and release of the guest. Reprinted with permission from Han, M.; Michel, R.; He, B.; Chen, Y.-S.; Stalke, D.; John, M.; Clever, G. H., Angew. Chem. Int. Ed. 2013, 52 (4), 1319–1323.

bonds to the thiophene rings, thus allowing rotation and hence conformational variation of both arms. In contrast to this, the closed-ring form of the ligand c-L24 is highly rigid. Heating either the open or closed ligand with PdII in a ratio of 2:1 resulted in the quantitative self-assembly of [Pd2L244] cages (Fig. 21B). The 1H NMR spectra of both [Pd2o-L244] and [Pd2c-L244] cages showed that all pyridine and thiophene signals were shifted downfield upon coordination with PdII. Interestingly, the 1H NMR spectrum of the closed cage contained three sets of pyridyl signals in a 1:2:1 ratio. As the C2-symmetric closed ligands are chiral (P or M), the resulting cages were found to contain statistical mixtures thereof, since all possible configurations were of similar energies as indicated by DFT calculations. Surprisingly, the structure obtained from single crystal X-ray diffraction studies consisted of a single stereoisomer containing both enantiomers of the ligand in a 2:2 ratio, indicating chiral discrimination during crystallization. The difference in the dimensions of the open and closed cages was evident from DOSY NMR experiments and the hydrodynamic radii were measured to be 7.04 and 8.67 Å for the open and closed cages, respectively. As with the free ligand, the reversible photoswitching between the open [Pd2o-L244] and closed [Pd2c-L244] cage was achieved smoothly. The host–guest properties were investigated with a suitable guest such as the dodecafluorododecaborate anion [B12F12]2  (Fig. 21C). 1H NMR spectroscopic titrations showed that the addition of [B12F12]2  resulted in significant signal shifting of both the open and closed-cages, particularly the protons directed toward the cavity. In the case of the open cage, 19F NMR spectroscopy showed that the signal of [B12F12]2  is shifted downfield, corresponding to the encapsulated species. Additionally, HRMS

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supported the formation of a 1:1 host–guest complex. The association constants of both the open and closed cages were calculated, and a significant difference in their affinities was observed, with the open cage [Pd2o-L244] showing a much stronger affinity for [B12F12]2  (Kopen ¼ 3.2  104 M 1) than the closed cage [Pd2c-L244] (Kclosed ¼ 6.7  102 M 1). The structural flexibility and shorter Pd-anion distances in the open cage were thought to account for the large difference in binding strengths. Although a Van’t Hoff analysis revealed that encapsulation is endothermic (DH o-C ¼ 30 kJ mol 1, DH c-C ¼ 0.6 kJ mol 1) and entropy-driven (DS o-C ¼ 187 J K 1 mol 1, DS c-C ¼ 56 J K 1 mol 1) in both cases, this indicates that release of solvent molecules from the cavity is an important factor in the encapsulation processes. Photoswitching of the host–guest complexes was also possible, thus enabling the modulation of the host–guest equilibrium using light as an external stimulus.

6.13.4.2

Light-Triggered Structural Reorganization

Recently, the Clever group reported a light-driven complete structural rearrangement of a small self-assembled [Pd3L256] ring into a large rhombicuboctahedral [Pd24L2548] sphere (Fig. 22).52 The ligand was also based on a photochromic dithienylethene (DTE) core, but had shorter and para-substituted pyridyl donors compared to the previous ligand (meta-substituted arms). Heating the open ligand with 0.5 equivalents of [Pd(CH3CN)4](BF4)2 for 1 h at 70 C resulted in the formation of two products in a 3:1 ratio. This mixture of products was identified as three- and four-membered rings [Pd3o-L256] and [Pd4o-L258], respectively. However, when Pd(NO3)2∙ H2O was used no evidence of the [Pd4o-L258] species was observed by NMR spectroscopy and mass spectrometry, indicating anion templation was playing a role in the formation of the larger ring. Calculations suggested that the [Pd3o-L256] assembly adopts a C3-symmetric structure, with one thiophene methyl substituent directed inwards toward the adjacent ligand and the other is directed away. As the 1H NMR spectrum of [Pd3o-L256] gave a single set of signals, the ligands must undergo fast flipping between two energetically degenerate enantiomeric forms. Conversion of the open ligand to the closed form was achieved by irradiation with 313 nm light. The closed form ligand was also heated with 0.5 equivalents of [Pd(CH3CN)4](BF4)2. The anticipated downfield shift of all aromatic protons was observed in the 1H NMR spectrum, but this was accompanied with significant signal broadening. With the aid of diffusion-ordered spectroscopy, the reaction was found to give a single product with a large hydrodynamic radius of approximately 3.5 nm. A large rhombicuboctahedral sphere of the formula [Pd24c-L2548] was identified. This was in accordance with the geometric considerations of the ligands, as the bend angle of the ligand was calculated to be 138.2 degrees (DFT EDF2/ 6-31G*), and according to work by Fujita et al., the transition from smaller [Pd12L2524] to larger [Pd24L2548] spheres occurs when the ligand bend angle is 130–134 degrees. The broad 1H NMR signals of the large [Pd24c-L2548] sphere were attributed to the fact that the ligand was chiral and racemic, and therefore the self-assembly mixture contained hundreds of stereoisomers. Indeed, chiral resolution of the ligands and subsequent formation of the homochiral cage reduced the amount of signal broadening

Figure 22 (A) Self-assembly, structural conversion, and comparison of photoswitching kinetics of ligand L25 giving (B) the self-assembled ring [Pd3o-L256] and (C) the rhombicuboctahedral sphere [Pd24c-L2548]. Reprinted with permission from Han, M.; Luo, Y.; Damaschke, B.; Gómez, L.; Ribas, X.; Jose, A.; Peretzki, P.; Seibt, M.; Clever, G. H., Angew. Chem. Int. Ed. 2016, 55 (1), 445–449.

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Figure 23 (A) Synthesis of interlocked cage [Pd6(tmen)6L264]12 þ. (B) Reversible intermolecular photodimerization of two molecules of interlocked cages. Reprinted with permission from Samanta, D.; Mukherjee, P. S., J. Am. Chem. Soc. 2014, 136 (49), 17006–17009. Copyright 2014 American Chemical Society.

in the 1H NMR spectrum and scalar coupling became evident. Interconversion of the rings and spheres was possible, although switching from open to closed and the concomitant [Pd3o-L256] to [Pd24c-L2548] transformation was found to be extremely slow, whereas the reaction in the reverse direction was significantly faster. The photoisomerization rate of the free ligands as well as the previously reported [Pd2L244] cage occurs on a similar timeframe, with the photoreaction being complete within minutes. The slower photoisomerization rate of the ligands in the [Pd3o-L256] ring was attributed to the conformational restrictions imposed by this structure. The photoisomerization proceeds through a Woodward–Hoffmann-allowed antarafacial, conrotatory 6-electron electrocyclic reaction, which is only possible from the anti-parallel conformation. The ligand backbone in the [Pd3o-L256] ring adopts a twisted conformation and unfavorable orbital overlap, thus prohibiting photocyclization. However, due to the system being in equilibrium between the free ligand and ring structure, photocyclization of the trace amounts of the free ligand (steady-state equilibrium concentration) occurs, resulting in a slow shift in the equilibrium and formation of the [Pd24c-L2548] spheres, taking about 15 h. Photoisomerization of the [Pd24c-L2548] spheres was completed quickly, resulting in the [Pd24oL2548] intermediate that slowly disassembles to reform the entropically favored ring structures in a thermally controlled process. In comparable work, Yoshizawa reported an [M2L2] tube synthesized from AgI hinges and bispyridine ligands with embedded anthracene panels.9 The tube was capable of binding fullerene C60. Disassembly of the tubular host was achieved by irradiation with UV–vis light, releasing the fullerene guest. In 2014, the group of Mukherjee presented a unique interpenetrated dimeric cage that was shown to undergo a light-initiated post-assembly modification. The triply interlocked [Pd6(tmen)6L264]12 þ double cage was obtained from a two-component selfassembly reaction with a cis-protected Pd(tmen)(NO3)2 salt and an olefin-containing 1,3,5-tris[(E)-2-(pyridin-3-yl)vinyl]benzene ligand (Fig. 23A).53 Analysis of the double-cage crystal structure revealed that two adjacent double cages were arranged in a head-totail manner, where two of the neighboring alkenes directly face each other. In the solid state, these neighboring olefins were measured to 3.7 Å apart. Consequently, the interpenetrated [M3L262]2 double cage was amenable to photoreactions. Exposing crystals of the double cage to sunlight or irradiating with UV light resulted in a [2 þ 2] cycloaddition between two adjoining double cages (Fig. 23B). The cycloaddition was reversible and cleavage of the cyclobutane ring connecting the two double cages occurred under thermal conditions in water.

6.13.5

Conclusion

The emergence of highly complex self-assembled structures that are responsive to various stimuli has recently become a major point of interest in the progressing field of supramolecular chemistry. Among this diverse category of supramolecular structures, selfassembled cages take a special role due to their unusual cavity environment that is capable of binding guest molecules. As coordination-driven cages have already been studied intensively, important principles have been established, demonstrating the proper use of the ligand design as well as the coordination geometry of the metal. This has enabled the evolution of cage structures

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that demonstrate stimuli-responsive behavior. Interpenetrated double-cage architectures were shown to be among the most versatile structural motifs for the implementation of such switchable features.54 Environmental influences such as counter anions, templating guest molecules, concentration, solvent effects, competitive ligands, oxidation/reduction, and light have been shown to affect cages, their guest-binding propensities, and in some cases, result in drastic structural changes. The ongoing development that is focused on increasing the complexity of coordination cages endeavors to create and implement systems with multiple cooperative functionalities. Nanoscopic self-assembled systems are especially relevant structures as platforms for multifunctionalization due to the close proximity of the ligand and the possibility to introduce different components. Combining functionality could be implemented, for example, with ligands featuring chirality and catalytic activity, redox activity, and photochromic properties. Thus, current research in this area is moving from simpler non- and monofunctionalized compounds toward structurally and functionally more complex architectures with stimuli-responsive features that are promising candidates for applications in molecular diagnostics, nano-medicine, separation techniques, catalysis, molecular electronics, and materials science.

Acknowledgments We thank the Alexander von Humboldt Foundation and DFG (CL 489/2-1) for financial support.

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Structural Transformations in Coordination Cages

44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54.

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