Highly emissive supramolecular oligo(p-phenylene vinylene) dendrimers

pi-Conjugated oligo(p-phenylene vinylene) (OPV) guest molecules for interaction with dendritic hosts were synthesized and fully characterized by NMR spectroscopy, MALDI-TOF-MS, elemental analysis and optical measurements. The binding properties of the five different OPV guests to a N,N-bis[(3-adamantyl ureido) propyl] methylamine host have been investigated. The guests that contained an aryl urea glycine spacer were bound with the highest association constant. Subsequently, an adamantyl urea modified fifth generation poly(propylene imine) dendrimer was synthesized as a multivalent host which contains 32 N,N-bis[(3-adamantyl ureido) propyl] amine binding sites. Size exclusion chromatography showed that 32 of the OPV guests strongly bind to the fifth generation adamantyl functionalized dendritic host. In the case of the supramolecular dendritic host/guest system smooth homogeneous thin films could be obtained by spin coating. The dendritic guest-host complexes showed a significantly higher emission upon binding then that of the individual molecules due to the three-dimensional orientation of the OPV guest molecules. In the solid state, this enhancement in luminescence was a factor of 10. The pi-conjugated oligomers are less aggregated in the supramolecular assemblies presumably because of a shielding effect of the bulky adamantyl units present in the hosts.     

Equilibrium isotope effects on noncovalent interactions in a supramolecular host-guest system

The self-assembled supramolecular complex [Ga(4)L(6)](12-) (1; L = 1,5-bis[2,3-dihydroxybenzamido]naphthalene) can act as a molecular host in aqueous solution and bind cationic guest molecules to its highly charged exterior surface or within its hydrophobic interior cavity. The distinct internal cavity of host 1 modifies the physical properties and reactivity of bound guest molecules and can be used to catalyze a variety of chemical transformations. Noncovalent host-guest interactions in large part control guest binding, molecular recognition and the chemical reactivity of bound guests. Herein we examine equilibrium isotope effects (EIEs) on both exterior and interior guest binding to host 1 and use these effects to probe the details of noncovalent host-guest interactions. For both interior and exterior binding of a benzylphosphonium guest in aqueous solution, protiated guests are found to bind more strongly to host 1 (K(H)/K(D) > 1) and the preferred association of protiated guests is driven by enthalpy and opposed by entropy. Deuteration of guest methyl and benzyl C-H bonds results in a larger EIE than deuteration of guest aromatic C-H bonds. The observed EIEs can be well explained by considering changes in guest vibrational force constants and zero-point energies. DFT calculations further confirm the origins of these EIEs and suggest that changes in low-frequency guest C-H/D vibrational motions (bends, wags, etc.) are primarily responsible for the observed EIEs.     

Synthesis and properties of new thiourea-functionalized poly(propylene imine) dendrimers and their role as hosts for urea functionalized guests

Five generations of poly(propylene imine) dendrimers have been modified by palmityl and adamantyl endgroups via a thiourea linkage. The synthesis of the thiourea dendrimers DAB-dendr-(NHCSNHAd)(n) and DAB-dendr-(NHCSNHC(16)H(33))(n) (n = 4, 8, 16, 32, 64) proceeds smoothly via the amino-terminated DAB dendrimer and the adamantyl and palmityl isothiocyanates, respectively. The properties of the thiourea dendrimers have been studied by IR and (1)H NMR, including relaxation (T1, T2) measurements. The thiourea dendrimers are used as multivalent hosts for a number of guest molecules containing a terminal urea-glycine unit in organic solvents. The host-guest interactions have been investigated using 1D- and NOESY-NMR. These investigations show that the guest molecules bind to the dendritic host via thiourea (host)-urea (guest) hydrogen bonding, and ionic bonding between the terminal guest carboxylate moiety and the outer shell tertiary amines of the dendrimer. The ability to bind guest molecules of the adamantyl- and palmitylthiourea dendrimers has been compared with their respective urea containing dendrimer analogues, by NMR-titration, and competition experiments. Upon complexation, the thiourea dendrimer hosts show a larger downfield NH shift than the corresponding urea dendrimer hosts, indicative of stronger hydrogen bonding in the complexed state. Furthermore, microcalorimetry has been used to determine binding constants for formation of the host-guest complexes; the binding constants are typically in the order of 10(4) M(-1). Both NMR and microcalorimetric studies show that the thiourea dendrimers bind the urea containing guests with somewhat higher affinity than the corresponding urea dendrimers.     

Multicomponent host-guest chemistry of carboxylic acid and phosphonic acid based guests with dendritic hosts: an NMR study

A new way to analyze supramolecular dendritic architectures is reported by making use of (13)C NMR and (31)P NMR. Two ethylene glycol guest molecules have been synthesized containing a (13)C labeled carboxylic acid headgroup (2) and a phosphonic acid headgroup (3). The binding of these guests to urea-adamantyl modified poly(propylene imine) dendrimers has been investigated with (13)C NMR and (31)P NMR next to 1D and 2D (1)H NMR techniques. Different amounts of guest 2 have been added to fifth generation dendrimer 1e, and the observed chemical shift values in (13)C NMR were fitted to a model that assumes 1:1 binding between guest and binding site. An association constant of 400 +/- 95 M(-)(1) is obtained for guest 2 with 41 binding sites per dendrimer. When different amounts of phosphonic acid guest 3 are added to dendrimer 1e, two different signals are observed in (31)P NMR. Deconvolution gives the fractions of free and bound guest, resulting in an association constant of (4 +/- 3) x 10(4) M(-)(1) and 61 +/- 1 binding sites. A statistical analysis shows that guest 2 forms a "polydisperse supramolecular aggregate", while guest 3 is able to form a "monodisperse supramolecular aggregate" when the amount of guest is high enough. The NMR results are compared with dynamic light scattering experiments, and a remarkable agreement is found. Phosphonic acid guest 3 is able to exchange with guest 2, which is in agreement with the obtained association constants, and shows that these techniques can be used to analyze multicomponent dendritic aggregates.     

Guest–host chemistry with dendrimers: Stable polymer assemblies by rational design

A new type of guest has been designed and synthesized for the exo‐type supramolecular functionalization of adamantyl‐urea‐terminated poly(propylene imine) dendrimers. This new type of guest motif features a uriedo methane sulfonic acid moiety that binds very selectively to the surfaces of dendrimers via a combination of noncovalent interactions forming well‐defined complexes. The guest–host properties have been examined for a fifth‐generation adamantyl‐urea‐functionalized poly(propylene imine) dendrimer capable of binding 32 guest molecules and for a model host molecule that can bind only one guest molecule. The guest–host chemistry has been studied with ¹H NMR spectroscopy, nuclear Overhauser enhancement spectroscopy NMR spectroscopy, T₁‐relaxation NMR experiments, and IR spectroscopy. The 1:32 ratio with the dendrimer has been confirmed unambiguously from ¹H NMR spectra of the complex after size exclusion chromatography. Competition experiments with guests bearing a carboxylic acid instead of a sulfonic acid in the binding motif have demonstrated that the sulfonic acid has superior binding strength. Also, the importance of a combination of noncovalent interactions has been shown via competition experiments with a guest lacking the uriedo moiety. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3792–3799, 2004     

Supramolecular recognition. Terpyridyl palladium and platinum molecular clefts and their association with planar platinum complexes

Molecular receptors, consisting of either two parallel cofacially disposed terpyridyl-Pd-Cl+ or terpyridyl-Pt-Cl+ units, are described. Concerted rotation of these units about the molecular spacer can alter their separation between 6.4 and 7.2 A to accommodate the dimensions of molecular guests. Neutral and anionic planar complexes of platinum(II) were investigated as guests to determine if metal-metal interaction between the host and guest metals could stabilize host-guest association. With a neutral guest, it was found that host-guest formation is signaled by a color change from light yellow to deep red. For one of the anionic guests, a visible absorption band appears upon host-guest formation with the platinum receptor that is ascribed to transitions associated with a Pt-Pt interaction. The association constants found for the neutral guest with the palladium and platinum receptors are large, suggesting that metal-metal interaction contributes to the molecular recognition. The structures of the host-(neutral)guest complexes in solution have been determined by 1H NOESY spectra. A crystal structure of the platinum host-(neutral)guest complex is the same as that found in solution and confirms the presence of a Pt-Pt interaction. Temperature-dependent (195)Pt NMR spectra in solution provide a quantitative estimate of the conformational interconversions of the free platinum receptor.     

Synthesis of carbosilane dendritic wedges and their use for the construction of dendritic receptors

A divergent route for the synthesis of carbosilane wedges that contain either a bromine or amine as focal point has been developed. These new building blocks enable the construction of various core-functionalized carbosilane dendrimers. As a typical example carbosilane dendrimers up to the third generation containing a N,N',N'-1,3,5-benzenetricarboxamide core (G1-G3) have been synthesized. This new class of molecules has been studied as host molecules and they have been found to bind protected amino acids as guest molecules via hydrogen bonding interactions. A decrease in the association constants was observed for the higher generation dendritic hosts, which is attributed to the increased steric hindrance around the core where the binding site is located. The binding properties of the dendritic host molecules can be tuned by modifying the binding motif at the core of the carbosilane dendrimers. A higher association constant for N-CBZ-protected glutamic acid 1-methyl ester (5) was observed when the third generation N,N',N'-1,3,5-tris(L-alaninyl)benzenetricarboxamide core-functionalized carbosilane dendrimer (G3') was used as the host molecule compared to G3. Different association constants for the formation of the diastereomeric G3'.L-5(K=295 M(-1)) and G3'.(D-5)(2) (K=236 M(-1)) host-guest complexes were observed, pointing to a small enantioselective recognition effect. The difference between the association constants for the formation of the G3'.(L-5)(2) and G3'.(D-5)(2) host-guest complexes was much more pronounced, K=37 M(-1)versus K=10 M(-1), respectively.     

Acid–Base Controllable Recognition Properties of a Highly Versatile Calix[6]crypturea

Versatile concave receptors with binding properties that can be controlled by external stimuli are rare. Herein, we report on a calix[6]crypturea ( 1 ) that features two different binding sites in close proximity, that is, a tris(2‐aminoethyl)amine (tren)‐based tris‐ureido cap that provides convergent hydrogen‐bond‐donor sites and a hydrophobic cavity suitable for the inclusion of organic guests. The binding properties of this heteroditopic receptor have been evaluated by NMR spectroscopic studies. Compound 1 behaves as a remarkably versatile host that strongly binds neutral molecules, anions, or contact ion pairs. Within each family of guests, compound 1 is able to discriminate between different guests with a high degree of selectivity. Indeed, neutral molecules that possess hydrogen‐bond donor and acceptor groups, chloride anions, and linear ammonium ions associated to F^? or Cl^? are particularly well recognized. In comparison with all the related receptors, compound 1 displays several unique features: 1) charged or neutral species are also recognized in polar or protic solvents, 2) thanks to the flexibility of the calixarene structure, induced‐fit processes allow the binding of large, biologically relevant ammonium salts such as neurotransmitters, and 3) the protonation of the basic cap leads to a positively charged receptor, 1? H⁺, which is reluctant to host anions and in which host properties are now governed by strong charge–dipole interactions with the guests. In other words, compound 1 presents an acid–base controllable tris‐ureido recognition site protected by a hydrophobic corridor that can select guests through induced‐fit processes. Thus, its versatile host properties can be allosterically controlled by protonation and selective guest‐switching processes are possible. To illustrate all these remarkable features, a sophisticated three‐pole supramolecular switch, based on the interconversion of host–guest systems displaying either charged or neutral guests, is described.     

Structural elucidation of dendritic host-guest complexes by X-ray crystallography and molecular dynamics simulations

The multiple monovalent binding of adamantyl-urea poly(propyleneimine) dendrimers with carboxylic acid-urea guests was investigated using molecular dynamics simulations and X-ray crystallography to better understand the structure and behavior of the dynamic multivalent complex in solution. The results from the two methods are consistent and suggest a preferred molecular picture of this complicated aggregate of multiple components. The guest molecules can bind to the dendrimer in a variety of ways although most involve hydrogen-bonding interactions between urea groups of the dendrimer with urea and/or carboxylic acid groups of the guest. In addition, acid-base interactions between the carboxylic acid of the guest and the tertiary amine in the interior of the dendritic host are present. Our proposed structure gives important information about the predominant dynamic interactions between the host and guest and illustrates how they fit together and interact with each other.     

Molecular recognition: minimizing the acid–base interaction of a tunable host–guest system changes the selectivity of binding

Two new receptors incorporating a 4-n-butyl aniline moiety has been designed, synthesized and evaluated for their binding properties towards a series of ureido-glycine derivatives. The host design is based on an urea adamantyl host motif known from large generations of poly(propylene imine) dendrimers functionalized with urea adamantyl moieties on the periphery. The design of the host molecules was directed towards a study of the effects of basicity of an amine function versus the effect of molecular recognition on the binding strength as seen from comparing the results obtained in the present work with previously guest–host studies. The guest–host interaction features an electrostatic interaction and multiple hydrogen binding interactions, where the main difference between the hosts described here and previously described is a substitution from an amine to aniline. Anilines are weaker bases than aliphatic amines and they generally give lower binding constants when treated with acidic guest molecules. The association constants have been measured using NMR titrations and the nature of the guest–host system is discussed based on these results. A general decrease in binding affinities is observed upon changing from the trialkyl amine hosts to the dialkyl aniline based hosts. One exception was observed where the weaker base host had stronger affinity to one of the guests. Thus, when the basicity of the host is decreased other factors influence the binding such as a better geometric fit. A crystal structure of one of the receptors has been solved and it shows no intramolecular hydrogen bonding.     

Noncovalent synthesis of supramolecular dendritic architectures in water

Water‐soluble guest–host complexes are prepared in a two‐step process. For this a new, polydisperse ethylene glycol containing guest molecule is synthesized that is soluble in both chloroform and water. This guest is able to bind to urea–adamantyl‐modified poly(propylene imine) dendrimers in chloroform in a noncovalent manner. When the chloroform is slowly evaporated and D₂O is added, the hydrophobic dendrimer is solubilized in water. This is not possible when the hydrophobic dendrimer is directly added to the hydrophilic guests in water. When the unmodified poly(ethylene glycol) starting material is used, no solubilization occurs, and this indicates that the urea–acetic acid head group is necessary to solubilize the dendrimer. Approximately 26 guests are required for solubilization of the dendrimer. A lower number of guests results in aggregation and precipitation of the dendrimer. A monodisperse guest molecule has been used in NMR studies to show that the guest molecule binds with its acidic head group to the periphery of the dendrimer. This methodology opens the way to functional dendrimer aggregates in aqueous media. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 6431–6437, 2005     

Guest-controlling effects on ER behaviors of beta-cyclodextrin polymer

An effective and novel approach to obtaining electrorheological particles with high performance through the formation of host-guest complexes has been achieved. The significant preponderance of the host-guest complex formation is that the host structure can be controlled easily by adding different guests. Based on this point, six supramolecular complexes of beta-cyclodextrin cross-linking polymer with salicylic acid (beta-CDP-1), 5-chlorosalicylic acid (beta-CDP-2), 3,5-dichlorosalicylic acid (beta-CDP-3), 5-nitrosalicylic acid (beta-CDP-4), 3,5-dinitrosalicylic acid (beta-CDP-5), or 3-hydroxy-2-naphthoic acid (beta-CDP-6) particles were synthesized. The electrorheological yield stresses of the suspensions of these particles in silicone oil have been investigated under DC electric fields. It was found that the yield stress of the typical beta-CDP-1 ER fluid was 5.6 kPa in 4 kV/mm, which is much higher than that of pure beta-cyclodextrin polymer (beta-CDP), that of pure salicylic acid as well as that of the mixture of the host with the guest. It is clearly indicated that the formation of supramolecular complexes between beta-CDP and salicylic acid can enhance the ER properties of the host. The similar results for other supramolecular complexes with different guests have also been obtained under the same DC electric fields. The yield stress of supramolecular complexes is strongly affected by the structure of guests. Among the six investigated guests, 3-hydroxy-2-naphthoic acid gave the highest ER property having a yield stress of 9.8 kPa under 4 kV/mm DC while cross-linked with beta-CDP to form beta-CDP-6. The yield stress of beta-CDP-6 was significantly increased by 72% in comparison with that of the pure beta-CDP. However, the yield stress of beta-CDP-1-5 slightly increased by 34-41% as compared with that of the pure beta-CDP. The achieved results indicate that the ER effect of host-guest complexes can be greatly affected by the changes of the tremendous guest structure, whereas the slight guest structural transposition, such as altering different groups of a guest, can only obtain the adjacent electrorheological behavior. The dielectric properties of these host-guest complexes also proved that the ER effect can be affected by the properties of guest.     

Dendrimer-tetrachloroplatinate precursor interactions. 2. Noncovalent binding in PAMAM outer pockets

Density functional theory is used to investigate the complexation ability of dendrimer outer pockets--in both tertiary amine protonated and unprotonated scenarios--toward molecular guests, particularly tetrachloroplatinate(II) and its mono- and diaquated derivatives as well as competing counterions. The effect of the outer pocket (host) on the binding affinity of guest molecules is analyzed and it is found that is more feasible for the host to accept species, particularly charged ones, inside an unprotonated pocket rather than outside; unlike the protonated pocket where the opposite is more likely to occur. Conformational changes triggered by the hosting of particular guests can have an impact in the global configuration of the larger dendrimer the pockets are part of.     

A cucurbit[6]uril analogue: host properties monitored by fluorescence spectroscopy

This paper describes the host properties of a new cucurbit[6]uril analogue, studied by fluorescence and 1H NMR spectroscopy. This host has an elongated cavity with oval-shaped portals. It is intrinsically fluorescent, and more importantly, this fluorescence is sensitive to guest encapsulation, allowing for the study of the inclusion of nonfluorescent guests by fluorescence spectroscopy. In the case of benzene as guest, significant enhancement of the cucurbit[6]uril analogue host fluorescence was observed upon addition of benzene; this allowed for the determination of the binding constant for 1:1 host-guest complexation, yielding a value of K = 6900 +/- 1100 M(-1). This complexation was also studied by 1H NMR, yielding a similar value of K = 8980 +/- 500 M(-1). The binding of a much larger guest, the dye Nile Red, was also studied, but in this case using guest fluorescence. Significant suppression of the Nile Red fluorescence was observed upon 1:1 complexation with the cucurbit[6]uril analogue, with an extremely large binding constant of 8.2 +/- 0.5 x 10(6) M(-1), indicating a very strong host-guest interaction and an excellent size and shape match. In both cases, binding was much stronger than in the case of the same guests with cucurbit[6]uril itself, and in the case of Nile Red, binding was also much stronger than with modified beta- or gamma-cyclodextrins. This is partly a result of the partial aromatic nature of the host walls, which allow for pi-pi interactions not possible in cucurbiturils or cyclodextrins. The ability to study its inclusion complexes using either host or guest fluorescence, and the very high binding constants observed, illustrates the versatility and potential usefulness of this new host compound.     

Shape-Adaptability and Redox-Switching Properties of a Di-Gold Metallotweezer

The use of a carbazolyl-connected di-gold(I) metallotweezer for the encapsulation of several electron-poor organic substrates, and a planar Au(III) complex containing a CNC pincer ligand, is described. The binding affinity of the receptor depends on the electron-deficient character of the planar guest, with larger association constants found for the more electron-poor guests. The X-ray diffraction molecular structures of two host:guest adducts show that the host approaches its arms in order to facilitate the optimum interaction with the surface of the planar guests, in a clear example of an guest-induced fit conformational arrangement. The electrochemical studies of the encapsulation of N,N’-dimethyl-naphthalenetetracarboxy diimide (NTCDI) show that the redox active guest is released from the receptor upon one electron reduction, thus constituting an example of redox-switchable binding.     

(Thio)ureido anion receptors based on a 1,3-alternate oxacalix[2]arene[2]pyrimidine scaffold

In pursuit of highly preorganized macrocyclic host molecules for the complexation of anions, a series of oxacalix[2]arene[2]pyrimidine-based bis(thio)ureido receptors were synthesized and fully characterized. The pincer-like 1,3-alternate conformation of the oxacalix[4]arene scaffold, essential for an efficient host-guest interaction, was visualized by single-crystal X-ray analysis and supported by variable-temperature NMR studies. The anion binding properties of the receptors were evaluated via (1)H NMR titration experiments, showing intermolecular interactions with H(2)PO(4)(-), AcO(-), BzO(-), and Cl(-) ions. The host molecule bearing 4-nitrophenyl substituents on the bisurea binding pocket showed association constants in the range of 200-400 M(-1) in the strongly competitive solvent mixture of DMSO/0.5% H(2)O.     

Cucurbit[7]uril host-guest complexes with small polar organic guests in aqueous solution

The host-guest stability constants for the inclusion of a series of small neutral polar organic guests in cucurbit[7]uril (CB[7]) have been determined in aqueous solution by (1)H NMR titrations. The dependence of the stability constant on the nature of the guests indicates that hydrophobic and dipole-quadrupole interactions are responsible for the binding. The complexation-induced chemical shift changes in the guest proton resonances, coupled with energy-minimization calculations, suggest that the guests are located such that their dipole moment is aligned perpendicular with the quadrupole moment of the CB[7] host. The stability constants for acetone and acetophenone decrease in the presence of Na(+) or K(+) cations as a result of cation capping of the CB[7] portals.     

Encapsulated guest-host dynamics: guest rotational barriers and tumbling as a probe of host interior cavity space

The supramolecular host assembly [Ga(4)L(6)](12-) (1; L = 1,5-bis[2,3-dihydroxybenzamido]naphthalene) encapsulates cationic guest molecules within its hydrophobic cavity and catalyzes a variety of chemical transformations within its confined interior space. Despite the well-defined structure, the host ligand framework and interior cavity are very flexible and 1 can accommodate a wide range of guest shapes and sizes. These observations raise questions about the steric effects of confinement within 1 and how encapsulation fundamentally changes the motions of guest molecules. Here we examine the motional dynamics (guest bond rotation and tumbling) of encapsulated guest molecules to probe the steric consequences of encapsulation within host 1. Encapsulation is found to increase the Ph-CH(2) bond rotational barrier for ortho-substituted benzyl phosphonium guest molecules by 3 to 6 kcal/mol, and the barrier is found to depend on both guest size and shape. The tumbling dynamics of guests encapsulated in 1 were also investigated, and here it was found that longer, more prolate-shaped guest molecules tumble more slowly in the host cavity than larger but more spherical guest molecules. The prolate guests reduce the host symmetry from T to C(1) in solution at low temperatures, and the distortion of the host framework that is in part responsible for this symmetry reduction is observed directly in the solid state. Analysis of guest motional dynamics is a powerful method for interrogating host structure and fundamental host-guest interactions.     

A simple method for the determination of enantiomeric excess and identity of chiral carboxylic acids

The association between an achiral copper(II) host (1) and chiral carboxylate guests was studied using exciton-coupled circular dichroism (ECCD). Enantiomeric complexes were created upon binding of the enantiomers of the carboxylate guests to the host, and the sign of the resultant CD signal allowed for determination of the configuration of the studied guest. The difference in magnitudes and shapes of the CD signals, in conjunction with linear discriminant analysis (LDA), allowed for the identity of the guest to be determined successfully. A model was created for the host-guest complexes which successfully predicts the sign of the observed CD signal. Further, Taft parameters were used in the model, leading to rationalization of the observed magnitudes of the CD signals. Finally, the enantiomeric excess (ee) of unknown samples of three chiral carboxylic acid guests was determined with an average absolute error of ±3.0%.     

Mechanism of host-guest complexation by cucurbituril

The factors affecting host-guest complexation between the molecular container compound cucurbit[6]uril (CB6) and various guests in aqueous solution are studied, and a detailed complexation mechanism in the presence of cations is derived. The formation of the supramolecular complex is studied in detail for cyclohexylmethylammonium ion as guest. The kinetics and thermodynamics of complexation is monitored by NMR as a function of temperature, salt concentration, and cation size. The binding constants and the ingression rate constants decrease with increasing salt concentration and cation-binding constant, in agreement with a competitive binding of the ammonium site of the guest and the metal cation with the ureido carbonyl portals of CB6. Studies as a function of guest size indicate that the effective container volume of the CB6 cavity is approximately 105 A(3). It is suggested that larger guests are excluded for two reasons: a high activation barrier for ingression imposed by the tight CB6 portals and a destabilization of the complex due to steric repulsion inside. For example, in the case of the nearly spherical azoalkane homologues 2,3-diazabicyclo[2.2.1]hept-2-ene (DBH, volume ca. 96 A(3)) and 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO, volume ca. 110 A(3)), the former forms the CB6 complex promptly with a sizable binding constant (1300 M(-1)), while the latter does not form a complex even after several months at optimized complexation conditions. Molecular mechanics calculations are performed for several CB6/guest complexes. A qualitative agreement is found between experimental and calculated activation energies for ingression as a function of both guest size and state of protonation. The potential role of constrictive binding by CB6 is discussed.