Effect of <Emphasis Type="Italic">ortho</Emphasis>-methyl groups in the benzene rings of the macrocyclic frame on the chemistry of phosphacavitands

Effect of ortho-methyl groups in the benzene rings of the macrocyclic matrix on the chemistry of cavitands with phosphorous amide bridges in the upper rim is studied. The presence of ortho-methyl groups is shown to prevent formation of phosphacavitands of C _4v symmetry and favor formation of macrocyclic systems of C _2v symmetry, enhance solubility of phosphacavitands in organic solvents, hinder oxidation of phospha(III)cavitands and decrease the yield of phospha(V)cavitands, prevent formation of binuclear molybdenum complexes of phosphorous amide cavitands, and favor formation of their tetranuclear analogs.     

Solvent effects in thermodynamically controlled multicomponent nanocage syntheses

The solvent effects on the condensation reaction between tetraformylcavitand 2 and ethylene-1,2-diamine 3 are reported. Earlier, it was found that the trifluoroacetic acid-catalyzed condensation of 2 and 2 equiv of 3 in CHCl(3) provides in 82% yield an octahedral nanocage 1 composed of 6 cavitands that are linked together by 12 -CH=N-CH(2)CH(2)-N=CH- linker groups (Liu, X.; Liu, Y.; Li, G.; Warmuth, R. Angew. Chem., Int. Ed. 2006, 45, 901). In tetrahydrofuran, the same reactants yield a tetrameric nanocage 4 (35% yield), which resembles a distorted tetrahedron built up from four cavitands that occupy the apexes. Each cavitand is doubly linked to one other cavitand and singly linked to the other two cavitands via -CH=N-CH(2)CH(2)N=CH- connectors. In CH(2)Cl(2), the reaction between 8 2 and 16 3 yields a square antiprismatic nanocage 5 (65% yield), in which each cavitand occupies one of the eight corners and is connected to four neighboring cavitands via -CH=N-CH(2)CH(2)-N=CH- linkers. Nanocage 5 is also the main product in CH(2)ClCH(2)Cl (26% yield) and CHCl(2)CHCl(2) (33% yield). Reduction of all imine bonds in 4 and 5 yields polyaminonanocontainers 7 and 8, respectively, which were isolated as trifluoroacetate salts. Contrary to the formation of larger capsules composed of four, six, or eight cavitands in the reaction between 2 and 3, the acid-catalyzed reaction of 2 with 2 equiv of H(2)N-X-NH(2) (X = (CH(2))(n)(=3,4,5), 1,3-C(6)H(4), 1,4-(CH(2))(2)C(6)H(4), or 1,3-(CH(2))(2)C(6)H(4)) quantitatively yields octaiminohemicarcerands 9-14, in which two cavitands are connected with four -CH=N-X-N=CH- linkers. The outcomes of these condensation reactions are rationalized with the different diamine structures and the relative orientation of cavitands in 1, 4, 5, and 9-14.     

Pore formation in phospholipid bilayers by amphiphilic cavitands

Five new cavitands were prepared that have four pendant n-undecyl chains and "headgroups" connected by 2-carbon spacers. The headgroups were ~OCH(2)CONH-Ala-OCH(3), 1; ~OCH(2)CONH-Phe-OCH(3), 2; ~OCH(2)CONH-Ala-OH, 3; ~OCH(2)CONH-Phe-OH, 4; and ~OCH(2)CONHCH(2)CH(2)-thyminyl, 5. Pore formation by each cavitand was studied by use of the planar bilayer conductance experiment. All five compounds were found to form pores in asolectin bialyer membranes. Compounds 1-3 behaved in a generally similar fashion and exhibited open-close dynamics. Compounds 4 and 5 formed pores more rapidly, were more dynamic, and led more quickly to membrane rupture. Differences in the ion transport activity are rationalized in terms of structure and aggregate cavitand assemblies.     

Self-complexed deep cavitands: alkyl chains coil into a nearby cavity

[structure: see text]. A series of self-complexing tetrabenzimidazole cavitands have been synthesized. Alkyl chains appended to the rim helically coil into the cavity in competitive organic solvents. These "flexible arms" exchange with each other, a process shown by 2D NMR to proceed via an intermediate solvent-containing species.     

Synthesis, structure, fullerene-binding and resolution of C3-symmetric cavitands with rigid and deep cavities

An efficient palladium-catalyzed Suzuki-Miyaura coupling method involving the reaction between CTV-Br(3) and a variety of aryl and heteroaryl boronic acids in the presence of indolyl phosphane ligands has been developed. This reaction procedure provided a series of C(3)-symmetric aryl-extended rigid cavitands for the first time. X-ray crystal structure analysis revealed that the phenyl substituted cavitand 5a has much larger rim edges and cavity height. This macrocyclic host adopts a linear head-to-tail "hand-shake" self-inclusion arrangement in the crystalline state. The fluorescence of 5a was considerably quenched upon the addition of C(60), with a binding constant of 78,700 ± 2300 dm(3) mol(-1) and a 1:1 stoichiometry according to the Job's plot. The interaction of C(60) with 5a in the excited state is stronger than that with CTV, which could be attributed to more binding sites in the extended arms of 5a. Moreover, optically active C(3)-symmetric cavitands (+)- and (-)-6 were easily obtained with high efficiency through chemical resolution.     

Cyclic Phosphorochloridites and Phosphorochloridates Derived from Bromocalix[4]resorcinolarenes

Reactions of bromocalix[4]resorcinolarenes with PCl₃ and POCl₃ in the presence of triethylamine give the corresponding phosphorochloridito and phosphorochloridato cavitands in good yields. Phosphorochloridito cavitands were converted into phosphoramidito cavitands by treatment with piperidine.     

A new [4]carceplex, and a crystal structure and dynamic combinatorial chemistry of a [5]carceplex

A new [4]carceplex (2·guest) is reported. It is composed of two cavitands linked by four disulfide bonds. It forms twistomers, which interconvert on a millisecond timescale. The energy barrier for interconversion of twistomers is guest-dependent. Formation of [4]carceplex 2·guest is template dependent. The selectivity in templates is flat relative to most previous related template work. Larger kin [5]carceplex 1·guests were reinvestigated. A crystal structure confirms the twist between the hemispherical cavitands. Use of a redox buffer allowed dynamic combinatorial chemistry to be performed between pairs of templates.     

‘Cloverleaf’ crown ether resorcin[4]arenes

Crown ether resorcin[4]arenes 1a, 1b, and 2b with a novel connectivity have been prepared from diquinoxaline cavitands in yields of 68%, 73%, and 25%, respectively. The reaction involves bridging the contiguous oxygen atom pairs with tri-, tetra- or pentaethylene glycol ditosylates.     

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.     

A versatile and modular approach to functionalisation of deep-cavity cavitands via"click" chemistry

The surface modification of deep-cavity cavitands has been demonstrated by using the azide-alkyne "click" coupling to attach dendritic macromolecules or linear polymers onto their periphery. The resulting set of macromolecular cavitands exhibited tuneable solubility yet retained the ability to encapsulate guest molecules.     

Gold nanoparticles functionalized with deep-cavity cavitands: synthesis, characterization, and photophysical studies

In this report, we present methods of functionalization of AuNP's with deep-cavity cavitands that can include organic molecules. Two types of deep-cavity cavitand-functionalized AuNP's have been synthesized and characterized, one soluble in organic solvents and the other in water. Functionalized AuNP soluble in organic solvents forms a 1:1 host-guest complex where the guest is exposed to the exterior solvents. The one soluble in water forms a 2:1 host-guest complex where the guest is protected from solvent water. Phosphorescence from thiones and benzil included within heterocapsules attached to AuNP was quenched by gold atoms present closer to the guests included within deep-cavity cavitands. During this investigation, we have synthesized four new deep-cavity cavitands. Of these, two thiol-functionalized hosts allowed us to make stable AuNP's. However, AuNP's protected with two amine-functionalized cavitands tended to aggregate within a day.     

Synthesis and Conformational Switching of Partially and Differentially Bridged Resorcin[4]arenes Bearing Fluorescent Dye Labels. Preliminary Communication

We report the synthesis of modified Cram‐type cavitands bearing one or two fluorescent labels for single‐molecule spectroscopic studies of vase? kite conformational switching (Scheme 3). Syntheses were performed by stepwise bridging of the four couples of neighboring H‐bonded OH groups of resorcin[4]arene bowls (Schemes 2 and 3). The new substitution patterns enable the construction of a large variety of future functional architectures. ¹H‐NMR Investigations showed that the new partially and differentially bridged cavitands feature temperature‐ and pH‐triggered vase? kite conformational isomerism similar to symmetrical cavitands with four identical quinoxaline bridges (Table). It was discovered that vase? kite switching of cavitands is strongly solvent‐dependent.     

Expanding cavitand chemistry: the preparation and characterization of [n]cavitands with n>=4

The preparation of cavitands composed of 4, 5, 6, and 7 aromatic subunits ([n]cavitands, n=4-7) is described. The simple, two-step synthetic procedure utilized readily available starting materials (2-methylresorcinol and diethoxymethane). The two cavitand products having 4 and 5 aromatic subunits exhibited highly symmetric cone conformations, while the larger cavitands (n = 6 and 7) adopt conformations of lower symmetry. 1H NMR spectroscopic studies of [6]cavitand and [7]cavitand revealed that these hosts undergo exchange between equivalent conformations at room temperature. The departure of these two cavitands from cone conformations is related to steric crowding on their Ar-O-CH2-OAr bridges and is predicted by simple molecular mechanics calculations (MM2 force field). X-ray diffraction studies on single crystals of the [4]cavitand, [5]cavitand, and [6]cavitand hosts afforded additional experimental support for these conclusions.     

State-of-the-art and recent progress in resorcinarene-based cavitand

Compartmentalization in the biological world brings excellent efficiency and specificity to the formation of complex compounds, inspiring supramolecular chemists to continuously search for defined spaces that can mimic such natural binding sites. Bowl-shaped cavitands built up from resorcinarenes (RA) present rigid and preorganized concave surfaces, which are capable of mimicking the molecular recognition properties of enzymes. The versatile scaffold of RA endows the cavitand with terrific variety and excellent binding behavior. This review provides a comprehensive overview over the structural modification to date in the high attention field of RA-based cavitands development. Different strategies for synthesizing diverse cavitands, such as small cavity cavitands, wider cavity cavitands, deep cavity cavitands, biscavitands, and asymmetric cavitands, are discussed in details. Furthermore, insights into their applications including catalysis, separations and sensing are provided.     

One-dimensional void-space arrays constructed from a coordination polymer with bowl-like frameworks of cavitands

A one-dimensional coordination polymer of [Mn(II)(hfac)2] bridged by new bowl-like ligands of cavitands was prepared and the crystal structure was determined by X-ray crystal analysis. Ethyl acetate molecules are necessarily included as guest molecules in each of the void-space cavities of the cavitands, and then are held by weak interaction forces.     

Synthesis of calixarene-based cavitands and nanotubes by click chemistry

The synthesis of a variety of calixarene-based cavitands (capped and functional calixarenes) and calix nanotubes is easily performed in good to high yields using "click chemistry" methodology through the Cu(I)-catalyzed ligation of adequate bis-alkyne and bis-azide derivatives.     

Diastereoselective formation of host-guest complexes between a series of phosphate-bridged cavitands and alkyl- and arylammonium ions studied by liquid secondary-ion mass spectrometry

The reactions occurring between a new class of cavitands that carry up to four dioxaphosphocin binding units and alkyl- and arylammonium ions was investigated by liquid secondary-ion mass spectrometry (LSIMS). As the cavitands existed as distinct diastereomers with different spatial orientation of their binding groups, these geometrical differences proved to have a dramatic influence on their chemical properties, including their ability to form host-guest complexes. In practice, only the cavitands that carry at least three P=O groups oriented toward the inside of the cavity were demonstrated to be strong ligands toward organic ammonium ions, whereas those with only two converging binding groups (either adjacent or opposite in the cavitand structure) still formed host-guest complexes, but they were much weaker. Adjacent binding sites proved to be more effective in interacting with organic ammonium ions than those lying in opposite positions. The isomers with no converging P=O groups did not act as molecular receptors. Even the isomer with one group oriented toward the inside of the cavity did not form host-guest complexes, as the absence of synergistic hydrogen bonding made the interaction from inside the cavity energetically equivalent (or even less favorable) to the outside binding. The presence in the cavitand structure of substituents with an electron-donating character proved to increase the proton affinity of the P=O binding groups and, consequently, their binding energy. The strong proton affinity of the cavitands led to the formation of stable host-guest complexes, as confirmed by the collisionally activated dissociation experiments. Effects of steric hindrance were weak, at least for the cavitands with three converging P=O groups. This confirmed that the cavity has a wide and readily accessible opening. The relative complexation constants were measured for the various guests, yielding scales of relative affinity toward each cavitand. These relative constants may represent thermodynamic values referred to the matrix used in LSIMS experiments, namely 3-nitrobenzyl alcohol (NBA), provided that kinetically controlled selvedge processes are negligible. Absolute complexation constants could not be obtained on account of the unknown pH and the protonation constant in the NBA matrix.     

Highly selective palladium-catalyzed aminocarbonylation and cross-coupling reactions on a cavitand scaffold

Palladium-catalyzed aminocarbonylation and cross-coupling reactions (Suzuki-, Sonogashira-, Stille-coupling) served as highly efficient synthetic tools for the synthesis of novel, functionalized deepened cavitands. Unexpectedly high chemoselectivities towards tetrafunctionalized cavitands have been observed for all of these reactions even using coupling partners much below the stoichiometric amount. No significant formation of either the mono-, di- or trifunctionalized products was observed.     

Triptycene‐Roofed Quinoxaline Cavitands for the Supramolecular Detection of BTEX in Air

Two novel triptycene quinoxaline cavitands ( DiTriptyQxCav and MonoTriptyQxCav ) have been designed, synthesized, and applied in the supramolecular detection of benzene, toluene, ethylbenzene, and xylenes (BTEX) in air. The complexation properties of the two cavitands towards aromatics in the solid state are strengthened by the presence of the triptycene moieties at the upper rim of the tetraquinoxaline walls, promoting the confinement of the aromatic hydrocarbons within the cavity. The two cavitands were used as fiber coatings for solid‐phase microextraction (SPME) BTEX monitoring in air. The best performances in terms of enrichment factors, selectivity, and LOD (limit of detection) values were obtained by using the DiTriptyQxCav coating. The corresponding SPME fiber was successfully tested under real urban monitoring conditions, outperforming the commercial divinylbenzene–Carboxen–polydimethylsiloxane (DVB–CAR–PDMS) fiber in BTEX adsorption.     

Retention behavior of resorcinarene‐based cavitands on C8 and C18 stationary phases

The understanding of the retention behavior of large molecules is an area of interest in liquid chromatography. Resorcinarene‐based cavitands are cavity‐shaped cyclic oligomers that can create host–guest interactions. We have investigated the chromatographic behavior of two types of cyclic tetramers as analytes in high‐performance liquid chromatography. The experiments were performed at four different temperatures (15, 25, 35, 45°C) on two types of reversed stationary phases (C₈ and C₁₈) from two different manufacturers. We have found a huge difference between the retention of resorcinarenes and cavitands. In some cases, the retention factor of cavitands was even a hundred times larger than the retention factor of resorcinarenes. The retention of methylated derivates was two to four times larger compared to that of demethylated compounds on every column. The opposite retention behavior of the resorcinarenes and cavitands on the two types of stationary phases showed well the difference of the selectivity of the XTerra and BDS Hypersil columns. The retention mechanism was studied by the thermodynamic parameters calculated from the van't Hoff equation.