Encapsulation of Formaldehyde and Hydrogen Cyanide in an Open‐Cage Fullerene

Reaction of C₆₃NO₂(Ph)₂(Py) ( 1 ) with o‐phenylenediamine and pyridine produces a mixture of C₆₃H₄NO₂(Ph)₂(Py)(N₂C₆H₄) ( 2 ) and H₂O@ 2 . Compound 2 is a new open‐cage fullerene containing a 20‐membered heterocyclic orifice, which has been fully characterized by NMR spectroscopy, high‐resolution mass spectrometry, and X‐ray crystallography. The elliptical orifice of 2 spans 7.45 Å along the major axis and 5.62 Å along the minor axis, which is large enough to trap water and small organic molecules. Thus, heating a mixture of 2 and H₂O@ 2 with hydrogen cyanide and formaldehyde in chlorobenzene affords HCN@ 2 and H₂CO@ 2 , respectively. The ¹H NMR spectroscopy reveals substantial upfield shifts for the endohedral species (δ=?1.30 to ?11.30 ppm), owing to the strong shielding effect of the fullerene cage.     

Supramolecular Drug Delivery Systems Based on Water‐Soluble Pillar[n]arenes

Supramolecular drug delivery systems (SDDSs), including various kinds of nanostructures that are assembled by reversible noncovalent interactions, have attracted considerable attention as ideal drug carriers owing to their fascinating ability to undergo dynamic switching of structure, morphology, and function in response to various external stimuli, which provides a flexible and robust platform for designing and developing functional and smart supramolecular nano‐drug carriers. Pillar[n]arenes represent a new generation of macrocyclic hosts, which have unique structures and excellent properties in host–guest chemistry. This account describes recent progress in our group to develop pillararene‐based stimuli‐responsive supramolecular nanostructures constructed by reversible host–guest interactions for controllable anticancer drug delivery. The potential applications of these supramolecular drug carriers in cancer treatment and the fundamental questions facing SDDSs are also discussed.

     

Water‐Soluble Molecularly Imprinted Nanoparticles (MINPs) with Tailored,Functionalized, Modifiable Binding Pockets

Construction of receptors with binding sites of specific size, shape, and functional groups is important to both chemistry and biology. Covalent imprinting of a photocleavable template within surface–core doubly cross‐linked micelles yielded carboxylic acid‐containing hydrophobic pockets within the water‐soluble molecularly imprinted nanoparticles. The functionalized binding pockets were characterized by their binding of amine‐ and acid‐functionalized guests under different pH values. The nanoparticles, on average, contained one binding site per particle and displayed highly selective binding among structural analogues. The binding sites could be modified further by covalent chemistry to modulate their binding properties.     

Size‐Selective Encapsulation of Hydrophobic Guests by Self‐Assembled M4L6 Cobalt and Nickel Cages

Subtle differences in metal–ligand bond lengths between a series of [M₄L₆]^4? tetrahedral cages, where M=Fe^II, Co^II, or Ni^II, were observed to result in substantial differences in affinity for hydrophobic guests in water. Changing the metal ion from iron(II) to cobalt(II) or nickel(II) increases the size of the interior cavity of the cage and allows encapsulation of larger guest molecules. NMR spectroscopy was used to study the recognition properties of the iron(II) and cobalt(II) cages towards small hydrophobic guests in water, and single‐crystal X‐ray diffraction was used to study the solid‐state complexes of the iron(II) and nickel(II) cages.     

Modulating the Binding of Polycyclic Aromatic Hydrocarbons Inside a Hexacationic Cage by Anion–π Interactions

We report the template‐directed synthesis of BlueCage⁶⁺, a macrobicyclic cyclophane composed of six pyridinium rings fused with two central triazines and bridged by three paraxylylene units. These moieties endow the cage with a remarkably electron‐poor cavity, which makes it a powerful receptor for polycyclic aromatic hydrocarbons (PAHs). Upon forming a 1:1 complex with pyrene in acetonitrile, however, BlueCage?6 PF₆ exhibits a lower association constant K_a than its progenitor ExCage?6 PF₆. A close inspection reveals that the six PF₆^? counterions of BlueCage⁶⁺ occupy the cavity in a fleeting manner as a consequence of anion–π interactions and, as a result, compete with the PAH guests. This conclusion is supported by a one order of magnitude increase in the K_a value for pyrene in BlueCage⁶⁺ when the PF₆^? counterions are replaced by much bulkier anions. The presence of anion–π interactions is supported by X‐ray crystallography, and confirms the presence of a PF₆^? counterion inside its cavity.     

Self‐Assembled Hexanuclear Organometallic Cages: Synthesis,Characterization, and Host–Guest Properties

A series of iridium‐ and rhodium‐based hexanuclear organometallic cages containing 2,5‐dichloro‐3,6‐dihydroxy‐1,4‐benzoquinone, 9,10‐dihydroxy‐1,4‐anthraquinone, and 6,11‐dihydroxynaphthacene‐5,12‐dione ligands were synthesized from the self‐assembly of the corresponding molecular “clips” and 2,4,6‐tri(4‐pyridyl)‐1,3,5‐triazine ligands in good yields. These organometallic cages can form inclusion systems with a wide variety of π‐donor substrates, including coronene, pyrene, [Pt(acac)₂], and hexamethoxytriphenylene. The 1:1 complexation of the resulting supramolecular assemblies was confirmed by ¹H NMR spectroscopy. Large complexation shifts (Δδ>1 ppm) were observed in the ¹H NMR spectra of guests in the presence of cage [Cp*₆M₆(μ‐DHNA)₃(tpt)₂](OTf)₆ ( 6a ; M=Ir, tpt=2,4,6‐tri(4‐pyridyl)‐1,3,5‐triazine). The formation of discrete 1:1 donor–acceptor complexes, pyrene ?6 b (M=Rh), coronene ?6 a , coronene ?6 b , and [Pt(acac)₂] ?6 a was confirmed by their single‐crystal X‐ray analyses. In these systems, the most important driving force for the formation of guest–host complexes is clearly the donor–acceptor π???π stacking interaction, including charge‐transfer interactions between the electron‐donating and electron‐accepting aromatic components. These structures provide compelling evidence for the existence of strong attractive forces between the electron‐deficient triazine core and electron‐rich guest. The results presented here may provide useful guidance for designing artificial receptors for functional biomolecules.     

Selective Co‐Encapsulation Inside an M6L4 Cage

There is broad interest in molecular encapsulation as such systems can be utilized to stabilize guests, facilitate reactions inside a cavity, or give rise to energy‐transfer processes in a confined space. Detailed understanding of encapsulation events is required to facilitate functional molecular encapsulation. In this contribution, it is demonstrated that Ir and Rh‐Cp‐type metal complexes can be encapsulated inside a self‐assembled M₆L₄ metallocage only in the presence of an aromatic compound as a second guest. The individual guests are not encapsulated, suggesting that only the pair of guests can fill the void of the cage. Hence, selective co‐encapsulation is observed. This principle is demonstrated by co‐encapsulation of a variety of combinations of metal complexes and aromatic guests, leading to several ternary complexes. These experiments demonstrate that the efficiency of formation of the ternary complexes depends on the individual components. Moreover, selective exchange of the components is possible, leading to formation of the most favorable complex. Besides the obvious size effect, a charge‐transfer interaction may also contribute to this effect. Charge‐transfer bands are clearly observed by UV/Vis spectrophotometry. A change in the oxidation potential of the encapsulated electron donor also leads to a shift in the charge‐transfer energy bands. As expected, metal complexes with a higher oxidation potential give rise to a higher charge‐transfer energy and a larger hypsochromic shift in the UV/Vis spectrum. These subtle energy differences may potentially be used to control the binding and reactivity of the complexes bound in a confined space.     

Interpenetrated Cage Structures

This Review covers design strategies, synthetic challenges, host–guest chemistry, and functional properties of interlocked supramolecular cages. Some dynamic covalent organic structures are discussed, as are selected examples of interpenetration in metal–organic frameworks, but the main focus is on discrete coordination architectures, that is, metal‐mediated dimers. Factors leading to interpenetration, such as geometry, flexibility and chemical makeup of the ligands, coordination environment, solvent effects, and selection of suitable counter anions and guest molecules, are discussed. In particular, banana‐shaped bis‐pyridyl ligands together with square‐planar metal cations have proven to be suitable building blocks for the construction of interpenetrated double‐cages obeying the formula [M₄L₈]. The peculiar topology of these double‐cages results in a linear arrangement of three mechanically coupled pockets. This allows for the implementation of interesting guest encapsulation effects such as allosteric binding and template‐controlled selectivity. In stimuli‐responsive systems, anionic triggers can toggle the binding of neutral guests or even induce complete structural conversions. The increasing structural and functional complexity in this class of self‐assembled hosts promises the construction of intelligent receptors, novel catalytic systems, and functional materials.     

Induced Chiroptical Changes of a Water‐Soluble Cryptophane by Encapsulation of Guest Molecules and Counterion Effects

We report the synthesis of the water‐soluble cryptophanol derivative 1 and the study of the chiroptical properties of its two enantiomers (>99 % ee) by polarimetry, electronic circular dichroism (ECD), and vibrational circular dichroism (VCD). We show that cryptophanol 1 exhibits unusual chiroptical properties in water under basic conditions (pH>12). For instance, the shapes of the ECD and VCD spectra of 1 in water were strongly dependent on the nature of the alkali metal ions (Li⁺, Na⁺, K⁺, Cs⁺) surrounding the cryptophane and whether or not a guest molecule is present inside the cavity of the host. To the best of our knowledge, this is the first example in which the nature of these counterions governs the chiroptical properties of a host molecule. Moreover, specific ECD spectra were obtained depending on the size of the guest molecules. This makes 1 a good sensor for small neutral molecules in aqueous solvent. Finally, VCD experiments associated with DFT calculations show that the chiroptical changes can be directly correlated to the presence of charges close to the aromatic rings and with a conformational change of the alkyl chains upon encapsulation.     

Encapsulation of Metalloporphyrins in a Self‐Assembled Cubic M8L6 Cage: A New Molecular Flask for Cobalt–Porphyrin‐Catalysed Radical‐Type Reactions

The synthesis of a new, cubic M₈L₆ cage is described. This new assembly was characterised by using NMR spectroscopy, DOSY, TGA, MS, and molecular modelling techniques. Interestingly, the enlarged cavity size of this new supramolecular assembly allows the selective encapsulation of tetra(4‐pyridyl)metalloporphyrins (M^II(TPyP), M=Zn, Co). The obtained encapsulated cobalt–porphyrin embedded in the cubic zinc–porphyrin assembly is the first example of a catalytically active encapsulated transition‐metal complex in a cubic M₈L₆ cage. The substrate accessibility of this system was demonstrated through radical‐trapping experiments, and its catalytic activity was demonstrated in two different radical‐type transformations. The reactivity of the encapsulated Co^II(TPyP) complex is significantly increased compared to free Co^II(TPyP) and other cobalt–porphyrin complexes. The reactions catalysed by this system are the first examples of cobalt–porphyrin‐catalysed radical‐type transformations involving diazo compounds which occur inside a supramolecular cage.     

An Open‐Cage Fullerene That Mimics the C60H10 (5,5)‐Carbon Nanotube Endcap to Host Acetylene and Hydrogen Cyanide Molecules

Treatment of the open‐cage fullerene C₆₃H₄NO₂(Ph)₂(Py)(N₂C₆H₄) ( 1 ) with methanol at 150 °C results in an orifice‐enlargement reaction to give C₆₉H₈NO(CO₂Me)(Ph)(Py)(N₂C₆H₄) ( 2 ). The overall yield from C₆₀ to isolated 2 is 6.1 % (four steps). Compound 2 contains a 24‐membered elliptic orifice that spans 8.45 Å along the major axis and 6.37 Å along the minor axis. The skeleton of 2 resembles the hypothetic C₆₀H₁₀ (5,5)‐carbon nanotube endcap. The cup‐shaped structure of 2 is able to include water, hydrogen cyanide, and acetylene, forming H₂O@ 2 , HCN@ 2 , and C₂H₂@ 2 , respectively. The molecular structures of H₂O@ 2 and HCN@ 2 have been determined by X‐ray crystallography. The ¹H NMR spectra reveal substantial upfield shifts for the endohedral species, such as δ=?10.30 (for H₂O), ?2.74 and ?14.26 (for C₂H₂), and ?1.22 ppm (for HCN), owing to the strong shielding effects of the fullerene cage.     

Allyl‐Functionalized Dioxynaphthalene[38]Crown‐10 Macrocycles: Synthesis,Self‐Assembly,and Thiol‐ene Functionalization

Five dioxynaphthalene[38]‐crown‐10 ( DNP38C10 ) macrocycles bearing one, two, three, or four allyl moieties have been synthesized and their ability to spontaneously self‐assemble with methyl viologen to form [2]pseudorotaxanes has been evaluated. Association constants between methyl viologen and several of the allyl‐functionalized DNP38C10 macrocycles are found to be comparable to that of methyl viologen and unfunctionalized DNP38C10 , however, the enthalpic and entropic factors that underlie overall binding free energy vary systematically with increasing allyl substitution. These variations are explained through a combination of solution phase and solid‐state analysis of the macrocycles and their complexes. The utility of endowing DNP38C10 macrocycles with allyl moieties is further demonstrated by the ease with which they can be functionalized through thiol‐ene click chemistry.