Form and function of molecular cups and capsules

Molecular cups and capsules are fascinating species that continue to attract significant attention due to their versatility and wide-ranging applications. The most common approach to their synthesis or construction involves the use of pre-existing and at least semi-rigid cups, often in connection with metal coordination and guest encapsulation. Advanced multicomponent strategies for obtaining such compounds are presented in this issue, in addition to examples of cups and capsules assembled in a “de novo” fashion from 2D elements.

Starting from closely related building blocks such as calixarenes, cucurbiturils or porphyrins, as well as topologically directing metalloligands, the authors have obtained amazing structural variety and diversity in applications; the latter range from recognition, through unusual magnetic properties, to biological applications. With respect to the papers included in this issue, the application of cups and capsules typically relies on the exploitation of their inherent concave structural features, for example to form containers capable of complexation, or to create permanent porosity in solids. However, a second trend that uses cups as a reliable structural motif for further design is also evident. For example, the value of the external cup-shape of calixarenes and their tendency to form micelle-like aggregates has been exploited in the shrouding of elaborate metal-clusters. Additional features such as semi-rigidity or chemically dynamic character are of great value, as they allow the structures to modulate their properties “on demand”. A short summary of each paper is presented below, but we would like to take this opportunity to thank all of the authors for their outstanding contributions.

Ling, Sobolev and Raston (DOI: 10.1039/c5ce01920f) present multicomponent complexes based on p-sulfonatocalix[4]arenes that, depending on the guest molecule present, form capsules or semi-open cavities. In the presence of the small 1-butyl-3-methylimidazolium cation, the p-sulfonatocalix[4]arenes are bridged with Gd^III ions, forming a capsule that effectively confines the guest. In the presence of a bis-imidazolium cation, only one imidazole ring is included in the calixarene cavity without incorporation of Gd^III in the resulting assembly.

Gaeta and co-workers (DOI: 10.1039/c6ce00802j) have extended their work with resorcin[6]arene, presenting a structural study in which the molecule adopts a pinched-cone conformation akin to that found for the p-^tBu- and p-sulfonatocalix[6]arenes (amongst others). Crystallisation from ethyl acetate and toluene results in the formation of bis-molecular capsules, the assembly of which is facilitated by concerted H-bonding interactions.

Utilisation of calixarene cups for the complexation of cationic species is also presented by the groups of Ugozzoli and Secchi (DOI: 10.1039/c6ce00268d). In their paper, the authors present the synthesis of calix[4]arene semitubes, species constructed by lower-rim bridging of the host building blocks. These were then studied for the complexation of N-alkyl pyridinium ion pairs through ¹H NMR and UV-vis spectroscopy, proving their homoditopic character.

Lhoták and co-workers have continued their investigations concerning the bridging of calix[4]arenes via the upper-rim (DOI: 10.1039/c6ce00314a). In their paper, the authors show that bis-meta-mercuration enables double bridging at the upper-rim of calix[4]arenes locked in the cone conformation. The result of this is the isolation of unique, highly distorted host molecules capable of interacting with small guest molecules in markedly different ways.

The paper by Dalcanale and co-workers describes the study of two isomeric diphosphonate cavitands as hosts for L-lactic acid in solution and the solid state (DOI: 10.1039/c6ce00270f). Several techniques were used to elucidate the occurrence of multiple complementary host–guest interactions, all of which act in tandem to afford stable one-to-one complexes. As a result, these cavitands have potential applications in nanomechanical sensing devices.

The sensing of biogenic polyamines is of high importance, and the paper by Gattuso, Geremia, Parisi and co-workers explores the use of carboxylcalix[5]arenes as hosts for spermine and norspermine (DOI: 10.1039/c6ce00468g). Through elegant design, synthesis and assembly, the authors show that these guests fit snugly within dimeric capsules; this is facilitated by a highly regioselective proton-transfer mediated recognition/binding process.

In the highlight article by Ariga and co-workers, the authors discuss two major themes concerned with the concept of cavity nanoarchitectonics (DOI: 10.1039/c6ce00432f). The first focuses on manipulation of the cyclodextrin cavity with a particular emphasis on biomedical applications. The second theme discusses future challenges in the area with a general focus on constructing arrays/networks and mechanical motion, prior to discussion of the potential for these systems to act in molecule delivery or uptake.

Liao and co-workers (DOI: 10.1039/c6ce00028b) used the pre-existing cup of p-tert-butylthiacalix[4]arene for lower-rim coordination of Co^II ions. Further coordination of this secondary building unit (SBU or metalloligand) to bifunctional linkers led to the formation of nanoscale cages with tetrahedral or truncated octahedral geometry; these were obtained at different pH. Interestingly, the frameworks are anionic and have uncoordinated pyridyl N atoms. The authors have shown interesting sorption properties, not only towards N₂ gas, but also selective absorption of the cationic dye methylene blue versus rhodamine-B.

A similar synthetic strategy of using a pre-formed cup and subsequent lower-rim coordination chemistry has been applied by the groups of Wu and Hong in order to obtain high-nuclearity Nd^III clusters (DOI: 10.1039/c6ce00092d). In this case, lower-rim coordination of Nd^III ions is performed with p-tert-butylsulfonylcalix[4]arene, and these building units are connected through the additional coordination of phosphonates. Thanks to the unique shape of the calixarene, the polymetallic core is discrete and effectively shielded from the external environment. Oval-shaped Nd^III₁₀, rugby ball-like Nd^III₁₁ and irregular Nd^III₁₉ nanoscale clusters were synthesised, all of which show characteristic emissions in the NIR region and magnetic properties dominated by antiferromagnetic interactions.

Sanz, Lusby, Brechin and co-workers have used a different strategy to facilitate the assembly of several nanoscale (and in some cases heterometallic) metal–organic cubes possessing large internal volumes (DOI: 10.1039/c6ce00654j). Their approach involves the synthesis of a [CrL₃] metalloligand (where HL = 1-(4-pyridyl)butane-1,3-dione) that possesses the correct topologically directing character to allow it to act as the vertex of a cube. Reaction of this metalloligand with M^II cations (M = Cu or Co) results in the formation of the desired polyhedron with a secondary metal atom residing on each face. These spectacular new assemblies are proposed as hosts for a wide variety of guest species.

Cucurbituril has a structure containing a persistent disc-shaped cavity and is therefore an excellent platform for the construction of void-containing systems. The groups of Lindoy and Wei (DOI: 10.1039/c6ce00255b) have shown that the interaction of alkaline-earth metal ions with the symmetrical octamethyl-substituted cucurbituril, in the presence of [CdCl₄]²⁻/[Cd₂Cl₈]⁴⁻ anions, leads to the formation of coordination polymers in which all structure-driving interactions are outside the internal cavity of cucurbituril. The absorption profiles of vacuum-activated samples showed maximum absorption for methanol among other volatile solvents.

Redshaw, Wei, Xiao and co-workers (DOI: 10.1039/c6ce00134c) have investigated the coordination and interaction of a symmetrical tetramethyl-cucurbit[6]uril with a series of Ln^III ions under both neutral and acidic conditions. Through screening a variety of parameters, it was found that more acidic media promoted the formation of crystals of either complexes or adducts. The trends observed also suggest that these systems may be used to separate heavier Ln^III ions from their lighter counterparts and vice versa under neutral and acidic conditions, respectively.

Although the internal cavity of cucurbituril is not suitable for the complexation of complex metal-containing species, it is well suited for organic ions. For example, the group of Danylyuk demonstrated cavity complexation of a degradation product of the drug diminazene, namely the 4-aminobenzamidinium cation, whilst magnesium cations and even the original diminazene drug molecule were complexed externally (DOI: 10.1039/c6ce00257a).

Adaptability is a main advantage of semi-rigid architectures and allows for the adjustment of a host structure in order to facilitate the encapsulation of different guests at relatively low energetic cost. One such architecture, based on two rigid triptycene moieties bridged with flexible crown ether chains, is reported by Chen and co-workers (DOI: 10.1039/c6ce00204h). The authors show that “Russian doll”-like complexes are formed by a triptycene-polyether macrocycle that entraps two paraquat cations, which themselves are able to “sandwich” aromatic hydrocarbons.

The flexibility of a ligand can be a real advantage if its functionality relies on wrapping around the guest. Cup-shaped tripodal ligands that wrap around an anion are reported by Das and co-workers (DOI: 10.1039/c6ce00220j). It is interesting to note that the ligands are able to wrap around spherical anions such as Cl⁻ and F⁻, while, at least in the solid state, tetrahedral anions like SO₄²⁻ reside outside the cups.

Adaptability is also observed for a more rigid scaffold, in this case resorcin[4]arene with a very short lower-rim alkyl chain. The host C-methylresorcin[4]arene is seen to adapt the shape of its cavity to suit that of the guests in a more facile manner than other resorcin[4]arenes. Indeed, for complexation of aromatic N-oxides, the group of Rissanen (DOI: 10.1039/c6ce00240d) reports a range of host conformations depending on guest shape.

Nissinen and co-workers show that resorcin[4]arenes decorated at their upper-rims with thiacrown bridges form coordination polymers with silver ions via classical coordination and through argentophilic contacts (DOI: 10.1039/c6ce00243a). Solvent-occupied channels and discrete pockets were found between the polymer layers in the structures of the prevailing coordination polymers.

Biological activity is of central interest in papers from Therrien, Archibald and Redshaw and their respective groups. Therrien and co-workers synthesised large octanuclear metalla-assemblies in solution, which incorporate porphyrin panels, embelin-derived linkers and half-sandwich complexes of rhodium (DOI: 10.1039/c6ce00139d), the main interest being the potential application of such compounds as anticancer agents. This work took advantage of the size of the assemblies (potential EPR effect) and the presence of rhodium, which in recent years has been seen as a less toxic alternative to platinum-based drugs. Indeed, all complexes showed IC₅₀ values in the nanomolar range, inducing apoptosis in cancer cells. Because the complexes possess hydrophobic cavities, it can be envisioned that they may be used as hybrid drugs, as in addition to their anticancer activity, they could complex (and deliver) another hydrophobic drug molecule.

Water soluble complexes of lanthanides, especially Gd^III, are used in magnetic resonance imaging (MRI) contrast, so their toxicity is therefore of primary interest. Archibald, Redshaw and co-workers studied the biological properties and structures of complexes consisting of p-sulfonatocalix[4]arene, lanthanide ions (Tb^III, Gd^III and Eu^III) and cyclen-based macrocycles (DOI: 10.1039/c6ce00209a). The multicomponent complexes formed coordination polymers and proved to be relatively non-toxic.

De novo construction of cages in the solid state is a more demanding and therefore less popular approach. Such an approach is presented by the Kondo group, using flexible bis-benzimidazole-type neutral ligands coordinated to Cu^II ions (DOI: 10.1039/c6ce00267f). These compounds form M₂L₄-type cationic cages, incorporating an anion in the interior. An interesting finding is that the complexes exhibit exchange of the anions located outside the cage, therefore showing dynamic character. Although the compounds are insoluble in water, they are able to exchange anions between the solid and the aqueous solution. This way, the hydrophobic ClO₄⁻ anion can be removed from aqueous solution.

Exchange processes in pre-formed solids were also of interest to Kumari, Deakyne, Atwood and co-workers (DOI: 10.1039/c6ce00639f). In their paper, the authors investigate the in situ exchange of metal centres in zinc-seamed dimeric pyrogallol[4]arene capsules, a study inspired by a) the potentially interesting magnetic properties of mixed-metal nanocapsules and b) the success of similar work on gallium-seamed systems. However, in this case the zinc analogue was found to be very robust and resisted exchange.

Finally, an interesting and very unique example of generating chirality-dependent capsular voids in the solid state was reported by the groups of Janiak and Kwit (DOI: 10.1039/c6ce00256k). These voids were constructed using calixsalens, macrocycles synthesised by a reversible [3+3] reaction between trans-1,2-diaminocyclohexane and 2-hydroxy-1,3-isophthaldehydes. The authors report that, for a racemic diamine, the reaction proceeds with high fidelity chiral self-sorting, leading to the exclusive formation of homochiral macrocycles. This finding is already very unique, however interesting findings also arise from comparison of the crystal packing of racemic calixsalens with the optically pure analogues. Optically pure calixsalens form stacks of interpenetrating macrocycles in the solid state. Racemic calixsalens also form stacks in the solid state, however with alternating motifs: homochiral interpenetrated dimer/heterochiral capsule. Because the macrocycles possess well-defined inner cavities, the heterochiral capsule has a pocket that was found to contain two dichloromethane molecules.

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