Crystallization-controlled dynamic self-assembly and an on/off switch for equilibration using boronic ester formation

Macrocyclic boronic esters of different sizes can be prepared selectively from the same starting diboronic acid and 1,2-diol by means of an interesting dynamic self-assembly phenomena. More specifically, two kinds of macrocyclic boronic esters could be formed diastereoselectively and nearly quantitatively under neutral conditions by the addition of an appropriate guest molecule that acts as a template. Although a mixture of tetrol 1 and di(boronic acid) 2 in methanol gave only insoluble polymeric boronic esters, a soluble macrocyclic boronic ester, homo-[2+2], was obtained selectively in the presence of toluene as a guest molecule. Furthermore, when benzene was employed as a guest molecule, the selective formation of another macrocyclic boronic ester, hetero-[3+3], occurred. Interestingly, each of these macrocycles could be converted into the other in the presence of methanol and the appropriate guest molecule; however, under aprotic conditions, guest molecules encaged by the macrocyclic boronic ester could be exchanged without affecting its structure. Thus the presence or absence of a protic solvent could be used as a regulator to switch on or off the dynamic equilibrium of the system. In addition, investigation of the effect of reaction time, direct observation of the reaction mixture by NMR spectroscopy, and carrying out the reaction using optically active tetrol suggested that precipitation plays an essentially important role in the selective formation of the macrocyclic boronic esters. Thus, although both of [2+2] and [3+3] were present as solutes in the reaction mixture, the type of added guest molecule induced the selective precipitation of only one form of macrocyclic boronic ester, hence displacing the equilibrium of the system.     

Kinetic study for the inclusion complex of carboxylic acids with cyclodextrin by the ultrasonic relaxation method

Ultrasonic absorption coefficients in the frequency range of 0.8-95 MHz were measured in aqueous solutions containing both beta-cyclodextrin (beta-CD) (host) and butanoic acid (in its dissociated form and undissociated one) (guest). A single relaxational phenomenon was observed only when the solutes were coexisting, although no relaxation was found in the beta-CD solution or in the acid solutions. The absorption was also measured in a solution of pentanoic acid (dissociated form) with beta-CD, and single relaxation was detected. The ultrasonic relaxation observed in these solutions was due to a perturbation of a chemical equilibrium related to a reaction of an inclusion complex formed by the host and guest. The equilibrium constant was obtained from the dependence of the maximum absorption per wavelength on the guest concentration. The rate constant for the inclusion process of the guest into a cavity of beta-CD and that for the leaving process from the cavity were determined from the obtained relaxation frequency and the equilibrium constant. The standard volume change of the reaction was also computed from the maximum absorption per wavelength. These results were compared with those in solutions containing both beta-CD and different guest molecules. It was found that the hydrophobicity of guest molecules played an important role in the formation of the inclusion complex and also that the charge on the carboxylic group had a considerable effect on the kinetic characteristics of the complexation reaction.     

Effects of guest microparticles on the swelling behavior of polyacrylamide gels

We report the effects of guest particles on the swelling properties of bulk polyacrylamide gels. The guest particles were the spheres of poly(N‐isopropylacrylamide) gel with submicrometer diameter, which were synthesized by an emulsion‐polymerized reaction in water. Polyacrylamide gels were prepared by a free radical polymerization reaction, immobilizing the gel microparticles with different concentrations at gelation. The macroscopic swelling ratio of this hybrid gel in a cylindrical shape was measured as functions of temperature and acetone concentration. The presence of guest particles was found to strongly affect the swelling behavior in the bulk gels when the concentration of incorporated particles exceeded a threshold. The experimental results indicated that the macroscopic volume in response to the temperature change should be determined by the guest particles above the threshold. On the other hand, the hybrid gel could not evidently shrink by adding acetone when the concentration of guest particles exceeded the threshold. To make clear the distribution of guest particles in the bulk networks, the fractured surfaces of dried gels were imaged by tapping mode atomic force microscopy. The guest particles were found to aggregate in the bulk homogeneous networks to form microdomains with densely connected structure, which became larger with increasing particle concentration. The roles of bulk networks as well as guest particles on the swelling behavior of hybrid gels were qualitatively discussed on the basis of the incorporated structure of guest particles, depending on the concentration of guest particles. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 1696–1704, 2005     

Influence of Equilibration Time in Solution on the Inclusion/Exclusion Topology Ratio of Host–Guest Complexes Probed by Ion Mobility and Collision‐Induced Dissociation

Host–guest complexes are formed by the creation of multiple noncovalent bonds between a large molecule (the host) and smaller molecule(s) or ion(s) (the guest(s)). Ion‐mobility separation coupled with mass spectrometry nowadays represents an ideal tool to assess whether the host–guest complexes, when transferred to the gas phase upon electrospray ionization, possess an exclusion or inclusion nature. Nevertheless, the influence of the solution conditions on the nature of the observed gas‐phase ions is often not considered. In the specific case of inclusion complexes, kinetic considerations must be taken into account beside thermodynamics; the guest ingression within the host cavity can be characterized by slow kinetics, which makes the complexation reaction kinetically driven on the timescale of the experiment. This is particularly the case for the cucurbituril family of macrocyclic host molecules. Herein, we selected para‐phenylenediamine and cucurbit[6]uril as a model system to demonstrate, by means of ion mobility and collision‐induced dissociation measurements, that the inclusion/exclusion topology ratio varies as a function of the equilibration time in solution prior to the electrospray process.     

Molecular dynamics simulation of laser desorption of a fragment of protein kinase A from two MALDI matrices

We have carried out molecular dynamics simulations to study the desorption of a dephosphorylated fragment of protein kinase A from two matrices, sinapic acid (SA) and 2,5-dihydroxybenzoic acid (DHB), after laser excitation. We have examined the results as a function of the laser fluence and of the burial depth of the guest peptide in the matrices. In most cases, we found that the energy transferred from the matrix to the guest peptide was not sufficiently large to fragment the peptide. Exceptions occurred when the peptide was more buried. This finding suggested that protein analytes might be less likely to break into smaller fragments if they were placed closer to the surface of the matrix. We have also examined how likely the guest peptide could form small clusters with the matrix molecules and found that the results depended on the degree of burial of the peptide, on the laser fluence, and on which matrix was used. Generally, stable clusters were more likely to be formed for guest peptides that were more buried, at a lower laser fluence, and in the SA rather than the DHB matrix. In addition, we found that the DHB matrix was broken down more easily by the laser than the SA matrix.     

The big squeeze: guest exchange in an M4L6 supramolecular host

Guest exchange in an M4L6 supramolecular host has been evaluated to determine whether host rupture is required for guest ingress and egress. Two mechanistic models were evaluated: one requiring partial dissociation of the host structure to create a portal for guest passage and one necessitating deformation of the host structure to create a dilated aperture for guest passage without host rupture. Three related lines of inquiry support the nondissociative guest exchange mechanism. (a) Equally facile guest exchange is observed in labile ([Ga4L6]12-) and inert ([Ti4L6]8- and [Ge4L6]8-) hosts. (b) Molecular mechanics calculations demonstrate that the structural deformations required for enlargement of an M4L6 aperture in a nonrupture or nondissociative guest exchange mechanism are plausible. (c) As predicted by the calculations, CoCp*2+, a sterically demanding guest, significantly inhibits guest exchange. These results bring new insight to the application of the M4L6 supramolecular host for encapsulated reaction chemistry for which there are now several examples.     

Guest-to-host proton transfer in melatonin-beta-cyclodextrin inclusion complex by ionspray, fast atom bombardment and tandem mass spectrometry.

Ionspray (IS) and fast atom bombardment (FAB) positive ionization mass spectrometry (MS) of 1 : 1 beta-cyclodextrin (beta-CD)-melatonin (MLT) host-guest complex allowed the detection of gaseous protonated 1 : 1 beta-CD-MLT. Tandem MS collision-induced dissociation (CID) of such protonated 1 : 1 beta-CD-MLT species showed the proton (charge) to be retained to a significant extent by the host and by its cage fragmentation products, in spite of the higher proton affinity of MLT with respect to that of beta-CD. This requires an endothermic guest-to-host proton transfer to occur within the gaseous association. Collisional activation could be accounted for by the promotion of such an endothermic process; however, the proton affinity decrease of the guest determined by the loss of the elements of acetamide, which is a dominant MS dissociation reaction of pure protonated MLT, could also provide a rationale for such an endothermic guest-to-host proton transfer. This proposal parallels the reaction scheme we had previously formulated for the analogous MS and tandem MS behaviour of 1 : 1 beta-CD-5-methoxytryptamine inclusion complex with the protonated 5-methoxytryptamine guest undergoing deamination.     

Control of Surface Barriers in Mass Transfer to Modulate Methanol-to-Olefins Reaction over SAPO-34 Zeolites

Mass transfer of guest molecules has a significant impact on the applications of nanoporous crystalline materials and particularly shape-selective catalysis over zeolites. Control of mass transfer to alter reaction over zeolites, however, remains an open challenge. Recent studies show that, in addition to intracrystalline diffusion, surface barriers represent another transport mechanism that may dominate the overall mass transport rate in zeolites. We demonstrate that the methanol-to-olefins (MTO) reaction can be modulated by regulating surface permeability in SAPO-34 zeolites with improved chemical liquid deposition and acid etching. Our results explicitly show that the reduction of surface barriers can prolong catalyst lifetime and promote light olefins selectivity, which opens a potential avenue for improving reaction performance by controlling the mass transport of guest molecules in zeolite catalysis.     

Conditional Copper-Catalyzed Azide–Alkyne Cycloaddition by Catalyst Encapsulation

Supramolecular encapsulation is known to alter chemical properties of guest molecules. We have applied this strategy of molecular encapsulation to temporally control the catalytic activity of a stable copper(I)–carbene catalyst. Encapsulation of the copper(I)–carbene catalyst by the supramolecular host cucurbit[7]uril (CB[7]) resulted in the complete inactivation of a copper-catalyzed alkyne–azide cycloaddition (CuAAC) reaction. The addition of a chemical signal achieved the near instantaneous activation of the catalyst, by releasing the catalyst from the inhibited CB[7] catalyst complex. To broaden the scope of our on-demand CuAAC reaction, we demonstrated the protein labeling of vinculin with the copper(I)–carbene catalyst, to inhibit its activity by encapsulation with CB[7] and to initiate labeling at any moment by adding a specific signal molecule. Ultimately, this strategy allows for temporal control over copper-catalyzed click chemistry, on small molecules as well as protein targets.     

Conformationally imprinted receptors: atropisomers with "write", "save", and "erase" recognition properties

[reaction: see text] An atropisomeric receptor with "write", "save", and "erase" recognition properties is presented. The receptor adopts a complementary conformation when heating in the presence of an ethyl adenine-9-acetate guest molecule. This complementary hydrogen bonding conformation is "saved" upon cooling to room temperature due to the reestablishment of restricted rotation and is stable even upon removal of the guest. Finally, the atropisomeric receptor can be "erased" by heating in the absence of the guest.     

Impact of Multimeric Ferrocene-containing Cyclodecapeptide Scaffold on Host-Guest Interactions at a β-Cyclodextrin Covered Surface

Among non-covalent bonds, the host-guest interaction is an attractive way to attach biomolecules to solid surfaces since the binding strength can be tuned by the nature of host and guest partners or through the valency of the interaction. For that purpose, we synthesized cyclodecapeptide scaffolds exhibiting in a spatially controlled manner two independent domains enabling the multimeric presentation of guest molecules on one face and the other face enabling the potential grafting of a biomolecule of interest. In this work, we were interested in the β-cyclodextrin/ferrocene inclusion complex formed on β-CD monolayers functionalized surfaces. By using surface sensitive techniques such as quartz crystal microbalance and surface plasmon resonance, we quantified the influence of the guest valency on the stability of the inclusion complexes. The results show a drastic enhancement of the affinity with the gradual increase of guest valency. Considering that the sequential binding events are equal and independent, we applied the multivalent model developed by the Huskens group to extract intrinsic binding constants and an effective concentration of host.     

Activating Versatile Mechanoluminescence in Organic Host–Guest Crystals by Controlling Exciton Transfer

Mechanoluminescence (ML) materials are attracting increasing interest owing to promising applications in various areas. However, to date, it remains a major challenge to develop a precise and universal route to achieving organic ML materials. Herein, we show that ML can be easily realized in organic piezophotonic host–guest crystals, under conditions in which neither the host nor the guest is ML-active. The experimental and theoretical results reveal that excitons of the host generated by piezoelectricity can be harvested effectively by the guest for light emission, owing to the restraint of intersystem crossing process. Moreover, different host–guest crystals are constructed, wherein the emission color, intensity, color purity, and emission duration of ML can be manipulated. This work deepens our understanding of organic ML generation in piezophotonic host–guest crystals and provides an inspiring principle to design more organic ML materials.     

Artificial light-harvesting systems fabricated by supramolecular host–guest interactions

Recent progress on artificial light-harvesting systems fabricated by supramolecular host-guest interaction was summarized.     

Supramolecular control of split-GFP reassembly by conjugation of beta-cyclodextrin and coumarin units

The design of proteins whose structure and function can be manipulated by binding with specific ligands has been of great interest in the field of protein engineering. Some successful examples of small-molecule-dependent proteins have been reported, but their ligand-binding domains have mainly been limited to those derived from natural proteins. The introduction of synthetic components for ligand responsiveness may expand the versatility of small-molecule-dependent proteins. In this study, we designed and constructed a fragmented green fluorescent protein (split GFP) whose reassembly could be modulated by the non-natural supramolecular interaction. In the design of split GFP, beta-cyclodextrin (betaCDx) and coumarin units were introduced into a C-terminal fragment (residues 214-230) of split GFP. The C-terminal peptide with betaCDx and coumarin, DC-M2-betaCDx, which contains both host and guest moieties in the same peptide chain, formed an intramolecular inclusion complex in the absence of exogenous guest molecules. This interaction strongly inhibited reconstitution with the GFP N-terminal fragment (residues 2-214) (GFP 1-10 OPT). However, the addition of suitable guest molecules for betaCDx terminated the intramolecular host-guest interaction in the C-terminal peptide, leading to reassembly of the protein fragments and concomitant fluorescence recovery due to the formation of mature GFP. These results successfully demonstrated direct control of protein structure and function by application of synthetic supramolecular interaction to a fragmented protein. The combined system of fragmented protein and synthetic supramolecular elements is expected to be a useful and flexible strategy for regulation of protein structure and function via binding to synthetic ligands.     

Conditional Copper‐Catalyzed Azide–Alkyne Cycloaddition by Catalyst Encapsulation

Supramolecular encapsulation is known to alter chemical properties of guest molecules. We have applied this strategy of molecular encapsulation to temporally control the catalytic activity of a stable copper(I)–carbene catalyst. Encapsulation of the copper(I)–carbene catalyst by the supramolecular host cucurbit[7]uril (CB[7]) resulted in the complete inactivation of a copper‐catalyzed alkyne–azide cycloaddition (CuAAC) reaction. The addition of a chemical signal achieved the near instantaneous activation of the catalyst, by releasing the catalyst from the inhibited CB[7] catalyst complex. To broaden the scope of our on‐demand CuAAC reaction, we demonstrated the protein labeling of vinculin with the copper(I)–carbene catalyst, to inhibit its activity by encapsulation with CB[7] and to initiate labeling at any moment by adding a specific signal molecule. Ultimately, this strategy allows for temporal control over copper‐catalyzed click chemistry, on small molecules as well as protein targets.     

High-density chemical intercalation of zero-valent copper into Bi2Se3 nanoribbons

A major goal of intercalation chemistry is to intercalate high densities of guest species without disrupting the host lattice. Many intercalant concentrations, however, are limited by the charge of the guest species. Here we have developed a general solution-based chemical method for intercalating extraordinarily high densities of zero-valent copper metal into layered Bi(2)Se(3) nanoribbons. Up to 60 atom % copper (Cu(7.5)Bi(2)Se(3)) can be intercalated with no disruption to the host lattice using a solution disproportionation redox reaction.     

Toward Expanded Diversity of Host–Guest Interactions via Synthesis and Characterization of Cyclodextrin Derivatives

Researchers developing software to predict the binding constants of small molecules for proteins have, in recent years, turned to host–guest systems as simple, computationally tractable model systems to test and improve these computational methods. However, taking full advantage of this strategy requires aqueous host–guest systems that probe a greater diversity of chemical interactions. Here, we advance the development of an experimental platform to generate such systems by building on the cyclodextrin (CD) class of hosts. The secondary face derivative mono-3-carboxypropionamido-β-cyclodextrin (CP-β-CD) was synthesized in a one-pot strategy with 87% yield, and proved to have much greater aqueous solubility than native β-CD. The complexation of anionic CP-β-CD with the cationic drug rimantadine hydrochloride was explored using one- and two-dimensional nuclear magnetic resonance; NOESY analysis showed secondary face binding of the ammonium moiety of the guest, based on cross-correlations between the amic acid functionality and the side-chain of rimantadine. Isothermal titration calorimetry was furthermore used to determine the standard Gibbs energy and enthalpy for this binding reaction, and the results were compared with those of rimantadine with native β-CD.     

Vine-twining polymerization: a new preparation method for well-defined supramolecules composed of amylose and synthetic polymers

In this article we describe a new method of polymerization called "vine-twining polymerization" for preparation of well-defined supramolecules, which are amylose-polymer inclusion complexes. The method was achieved by enzymatic polymerization of alpha-D-glucose-1-phosphate catalyzed by phosphorylase in the presence of various synthetic polymers such as polyethers, polyesters, poly(ester-ether), and amphiphilic block copolymer. Powder X-ray diffraction (XRD) and 1H-NMR measurements determined the structures of the products to be inclusion complexes. The XRD patterns were completely different from those of amylose and guest polymers. The 1H-NMR spectra of the products indicated that the structures were composed of amylose and guest polymers. The formation process of the inclusion complexes during the enzymatic polymerization was also evaluated. In addition, we revealed that the bulkiness of the end groups and the hydrophobicity of the guest polymers strongly affected the formation of the inclusion complexes. By means of this method of polymerization, a graft polymer having inclusion complexes as side chains was prepared. Furthermore, as an evolution of the "vine-twining polymerization," we attempted a system of parallel polymerization to form an inclusion complex of amylose with a strongly hydrophobic guest polymer.     

Modulation of Protein Dimerization by a Supramolecular Host–Guest System

Two sets of cyan and yellow fluorescent proteins, monomeric analogues, and analogues with a weak affinity for dimerization were functionalized with supramolecular host–guest molecules by expressed protein ligation. The host–guest elements induce selective assembly of the monomeric variants into a supramolecular heterodimer. For the second set of analogues, the supramolecular host–guest system acts in cooperation with the intrinsic affinity between the two proteins, resulting in the induction of a selective protein–protein heterodimerization at a more dilute concentration. Additionally, the supramolecular host–guest system allows locking of the two proteins in a covalent heterodimer through the facilitated and selective formation of a reversible disulfide linkage. For the monomeric analogues this results in a strong increase of the energy transfer between the proteins. The protein heterodimerization can be reversed in a stepwise fashion. The trajectory of the disassembly process differs for the monomeric and dimerizing set of proteins. The results highlight that supramolecular elements connected to proteins can both be used to facilitate the interaction between two proteins without intrinsic affinity and to stabilize weak protein–protein interactions at concentrations below those determined by the actual affinity of the proteins alone. The subsequent covalent linkage between the proteins generates a stable protein dimer as a single species. The action of the supramolecular elements in concert with the proteins thus allows the generation of protein architectures with specific properties and compositions.     

Phenethylamine@Pillar[5]arene Biointerface for Highly Enantioselective Adsorption of Protein

In the life system, the biointerface plays an important role in cell adsorption, platelet adsorption and activation. Therefore, the study of protein adsorption on the biointerface is of great significance for understanding life phenomena and treatment in vitro. In this paper, a chiral biointerface was constructed by the virtue of host‐guest interaction between a water‐soluble pillar[5]arene (WP5) and phenethylamine (PEA) over a gold surface for adsorption of lysozyme proteins. From the experimental results it was identified that the host‐guest biointerface has a high adsorption capacity and strong chiral selectivity. Furthermotre, it was identified that the host‐guest interaction plays the decisive role in the enhancement of chirality of the interface, which was much beneficial for increasing protein adsorption and amplifying the capacity of chiral discrimination. Therefore, this work provides a new idea for the construction of biointerface materials with high protein adsorption capacity and high chiral selectivity through supramolecular interaction, which will have potential applications in the fields of biosensors, biocatalysts, biomaterials.