Efficient synthesis of calix[6]tmpa: a new calix[6]azacryptand with unique conformational and host-guest properties

A new C(3v)-symmetrical calix[6]azacryptand, that is, calix[6]tmpa (11), was synthesized by efficient [1+1] macrocyclization reactions. Remarkably, both linear and convergent synthetic strategies that were applied lead to equally good overall yields. Calix[6]tmpa behaves as a single proton sponge and appeared reluctant to undergo polyprotonation, unlike classical tris(2-pyridylmethyl)amine (tmpa) derivatives. It also acts as a good host for ammonium ions. Interestingly, it strongly binds a sodium ion and a neutral guest molecule, such as a urea, an amide, or an alcohol, in a cooperative way. A (1)H NMR study indicated that the ligand, as well as its complexes, adopt a major flattened cone conformation that is the opposite of that observed with the previously reported calix[6]cryptands. Characterization of the monoprotonated derivative 11H(+) by X-ray diffraction also revealed the presence of a 1,3-alternate conformation, which is the first example of its kind in the calix[6]arene family. This conformer is probably also present in solution as a minor species. The important covalent constraint induced by the polyaromatic tmpa cap on the calixarene skeleton, and conversely from the calix core onto the tmpa moiety, is the likely basis for the unique conformational and chemical properties of this host.     

Guest binding and orientation within open nanoscale hosts

The synthesis of three different nanoscale molecular hosts is reported. These cavitands each possess a highly preorganized cavity with an open portal (nearly 1 nm wide), by which guests can enter and egress the cavity. Additionally, these hosts are deep-functionalized with a crown of weakly acidic benzal C-H groups which can form a variety of noncovalent interactions with guest molecules residing within the cavity. Thirty-one guests were examined for their propensity to form complexes with the hosts. Guests that possess halogen atoms were the strongest binders, suggesting the formation of polydentate C-H triplebond X-R hydrogen bonds with the deep crown of benzal hydrogens. Exchange rates between the free and bound states were noted to be dependent on the size of the guest and the solvent used to study complexation. In general, stronger binding and slower exchange were noted for complexations carried out in DMSO with highly complementary guests. The orientation of each guest within the cavity was determined using either EXSY NMR spectroscopy or (1)H NMR shift data. Cumulatively these results showed that the principal factors directing orientation were interactions with the benzal groups and the type of solvent. Van't Hoff analyses of selected complexations were also carried out. As well as revealing that all complexations were entropically unfavorable, these experiments provided support for guest orientation determinations, and gave an estimation that the formation of a C-H triplebond I-R hydrogen bond releases between 1 and 1.5 kcal mol(-1).     

Electrochemically controlled formation/dissociation of phosphonate-cavitand/methylpyridinium complexes

The phosphorus-bridged cavitand 1 self-assembles very efficiently in CH2Cl2 with either the monopyridinium guest 2+ or the bispyridinium guest 3(2+). In the first case a 1:1 complex is obtained, whereas in the second case both 1:1 and 2:1 host-guest complexes are observed. The association between 1 and either one of the guests causes the quenching of the cavitand fluorescence; in the case of the adduct between 1 and 3(2+), the fluorescence of the latter is also quenched. Cavitand complexation is found to affect the reduction potential values of the electroactive guests. Voltammetric and spectroelectrochemical measurements show that upon one-electron reduction both guests are released from the cavity of 1. Owing to the chemical reversibility of such redox processes, the supramolecular complexes can be re-assembled upon removal of the extra electron from the guest. Systems of this kind are promising for the construction of switchable nanoscale devices and self-assembling supramolecular materials, the structure and properties of which can be reversibly controlled by electrochemical stimuli.     

Solvent exchange in thermally stable resorcinarene nanotubes

The assembly of C-methyl resorcinarene into a tubular supramolecular solid-state structure, its thermal stability, and its hosting properties are reported. Careful control of the crystallisation conditions of C-methyl resorcinarene and 1,4-dimethyl-1,4-diazoniabicyclo[2.2.2]octane (1,4-dimethyl DABCO) dibromide leads to a formation of two crystallographically different, but structurally very similar, solid-state nanotube structures. These structures undergo a remarkable variety of supramolecular interactions, which lead to the formation of 0.5 nm diameter nonpolar tubes through the crystal lattice. The formation of these tubes is templated by suitably sized small alcohols, namely, n-propanol, 2-propanol, or n-butanol. The self-assembly involves close pi...pi interactions between the adjacent resorcinarenes, and C--H...pi and cation...pi interactions between the resorcinarenes and the guest 1,4-dimethyl DABCO dications. The crystals of these supramolecular tube structures are thermally very stable and the included solvent alcohol can be removed from the tubes without breaking the single-crystalline structure of the assembly. After removal of the solvent molecules the tubes can be filled with other small, less polar solvent molecules such as dichloromethane.     

Nanofibers of fullerene C60 through interplay of ball-and-socket supermolecules

Mixing solutions of p-tBu-calix[5]arene and C(60) in toluene results in a 1:1 complex (C(60)) intersection(p-tBu-calix[5]arene), which precipitates as nanofibers. The principle structural unit is based on a host-guest ball-and-socket nanostructure of the two components, with an extended structure comprising zigzag/helical arrays of fullerenes (powder X-ray diffraction data coupled with molecular modeling). Under argon at temperatures above 309 degrees C, the fibers undergo selective volatilization of the calixarenes to afford C(60)-core nanostructures encapsulated in a graphitic material sheath, which exhibits a dramatic increase in surface area. Above 650 degrees C the material exhibits an ohmic conductance response, due to the encapsulation process.     

Supramolecular sensing with phosphonate cavitands

Phosphonate cavitands are an emerging class of synthetic receptors for supramolecular sensing. The molecular recognition properties of the third-generation tetraphosphonate cavitands toward alcohols and water at the gas-solid interface have been evaluated by means of three complementary techniques and compared to those of the parent mono- and diphosphonate cavitands. The combined use of ESI-MS and X-ray crystallography defined precisely the host-guest association at the interface in terms of type, number, strength, and geometry of interactions. Quartz crystal microbalance (QCM) measurements then validated the predictive value of such information for sensing applications. The importance of energetically equivalent multiple interactions on sensor selectivity and sensitivity has been demonstrated by comparing the molecular recognition properties of tetraphosphonate cavitands with those of their mono- and diphosphonate counterparts.     

Allosteric tuning of the intra-cavity binding properties of a calix[6]arene through external binding to a ZnII center coordinated to amino side chains

Molecular recognition by calix[6]arene-based receptors bearing three primary alkylamino side chain arms (1) is described. Complexation of Zn(II) ion provides the dinuclear mu-hydroxo complex 2G(OH), XRD characterization of which, together with solution studies, provided evidence of its hosting of neutral polar organic guests G. Treatment of this complex with a carboxylic acid or a sulfonamide (XH) results in the formation of mononuclear species 3G(X), one of which (X = Cl) has been characterized by XRD. A dicationic complex 3G(RNH2) is obtained upon treatment of 2G(OH) with a mixture of an alkylamine and a strong acid. Each of these Zn(II) complexes features a tetrahedral metal ion bound to the three amino arms of ligand 1 and to an exogenous ligand (either HO-, X-, or RNH2) sitting outside of the cavity. As a result, the metal ion structures the calixarene core, constraining it in a cone conformation suitable for guest hosting. The receptor properties of these compounds have been explored in detail and are compared with those of the trisammonium receptor 1G(3H+), based on the same calixarene core, as well as those of the trisimidazole-based dicationic Zn funnel complexes. This study reveals very different host properties, in spite of the common hydrophobic, pi-basic, and hydrogen-bonding acceptor properties of the calixarene cores. A harder external ligand produces a less polarized receptor that is consequently particularly sensitive to the hydrogen-bonding ability of its guest. The less electron-rich the apical ligand, and a fortiori the trisammonium host, the more sensitive the receptor to the dipole moment of the guest. All this stands in contrast with the funnel Zn complexes, in which the coordination link plays a dominant role. It is also shown that the asymmetry of an exo-coordinated enantiopure amino ligand is sensed by the guest. This supramolecular system nicely illustrates how the receptor properties of a hydrophobic cavity can be allosterically tuned by the environment.     

Cycloalkane and alicyclic heterocycle complexation by new switchable resorcin[4]arene-based container molecules: NMR and ITC binding studies

The synthesis and structural characterization of novel, "molecular basket"-type bridged cavitands is reported. The resorcin[4]arene-based container molecules feature well-defined cavities that bind a wide variety of cycloalkanes and alicyclic heterocycles. Association constants (K(a)) of the 1:1 inclusion complexes were determined by both (1)H NMR and isothermal titration calorimetry (ITC). The obtained K(a) values in mesitylene ranged from 1.7×10(2) M(-1) for cycloheptane up to 1.7×10(7) M(-1) for morpholine. Host-guest complexation by the molecular baskets is generally driven by dispersion interactions, C-H···π interactions of the guests with the aromatic walls of the cavity, and optimal cavity filling. Correlations between NMR-based structural data and binding affinities support that the complexed heterocyclic guests undergo additional polar C-O···C=O, N-H···π, and S···π interactions. The first crystal structure of a cavitand-based molecular basket is reported, providing precise information on the geometry and volume of the inner cavity in the solid state. Molecular dynamic (MD) simulations provided information on the size and conformational preorganization of the cavity in the presence of encapsulated guests. The strongest binding of heterocyclic guests, engaging in polar interactions with the host, was observed at a cavity filling volume of 63 ± 9%.     

Exploiting Cavities in Supramolecular Gels

Endowing supramolecular gelators with cavities opens up a number of opportunities not possible with other gel systems. The well‐established host–guest chemistry of cavitands can be utilized to build up and break down gel structures, introduce responsive functionalities, or enhance selectivity in applications such as catalysis and extraction. Cavity‐containing gelators provide an excellent case study for how different aspects of supramolecular chemistry can be used intelligently to create responsive materials.     

A combined experimental and theoretical study of the molecular inclusion of organometallic sandwich complexes in a cavitand receptor

We describe herein a detailed study of the inclusion processes of several positively charged organometallic sandwich complexes inside the aromatic cavity of the self-folding octaamide cavitand 1. In all cases, the binding process produces aggregates with a simple 1:1 stoichiometry. The resulting inclusion complexes are not only thermodynamically stable, but also kinetically stable on the (1)H NMR spectroscopy timescale. The binding constants for the inclusion complexes were determined by different titration techniques. We have also investigated the kinetics of the binding process and the motion of the metallocenes included in the aromatic cavity of the host. Using DFT-based calculations, we have evaluated the energies of a diverse range of potential binding geometries for the complexes. We then computed the proton chemical shifts of the included guest in each one of the binding geometries. The agreement between the averaged computed values and the experimentally determined chemical shifts clearly supports the proposed binding geometries that we assigned to the inclusion complexes formed in solution. The combination of experimental and theoretical results has allowed us to elucidate the origins of the distinct features detected in the complexation process of the different guests, as well as their different motions inside the host.     

Simulations of p-tert-butylcalix[4]arene with multiple occupancies of small guest molecules

Classical molecular dynamics simulations were used to study low-density beta(0)-phase p-tert-butylcalix[4]arene inclusion compounds with multiple calix occupancies of xenon, carbon dioxide, methane, and hydrogen guest molecules with guest-host ratios ranging from 1:4 to 4:1. Custom parameterized force fields were used for the guests and the AMBER force field for the calixarene units was validated in our previous work (Chem. Eur. J. 2006, 12, 5231). The inclusion energy and unit cell volume of the calixarene inclusion compound were determined for various guest occupancies and for occupancies greater than 1:1, strong guest-guest interaction effects are observed. The structure and energetics of the 2:1 CO(2)/beta(0)-phase inclusion compound were compared to those of the low-temperature 2:1 CO(2)/calixarene in which the guest molecules occupy both cage and interstitial sites.     

Host-guest-driven copolymerization of tetraphosphonate cavitands

The outstanding complexing properties of tetraphosphonate cavitands towards N‐methylpyridinium salts were exploited to realise a new class of linear and cyclic AABB supramolecular polymers through host–guest interactions. The effectiveness of the selected self‐association processes was tested by ¹H NMR studies, whereas microcalorimetric analyses clarified the binding thermodynamics and revealed the possibility of tuning entropic contributions by acting on the flexibility of the guest linker. Although the formation of linear polymeric chains for a rigid system was demonstrated by X‐ray analysis, the presence of a concentration‐dependent ring–chain equilibrium was indicated by solution viscosity measurements in the case of a very flexible ditopic BB guest co‐monomer.