Study of host–guest interaction between ß-cyclodextrin and alkyltrimethylammonium bromides in water

Cyclodextrins were found to play important roles in self-assembly systems of surfactants. The interactions between host molecule ß-cyclodextrin (CD) and model cationic surfactants, alkyltrimethylammonium bromides with different alkyl chain length: dodecyl-(C₁₂TAB), tetradecyl-(C₁₄TAB) and hexadecyl-(C₁₆TAB) are studied by means of conductivity measurements at 313.2 K. The data obtained indicate that inclusion complexes (CD:S⁺) had formed, and apparent critical micelle concentration (CMC*) is equivalent to the combined concentrations of surfactant monomers complexed with the CD and that of a free dissolved monomer in equilibrium with the micellized surfactant without CD. Inclusion complexes were characterized by an equilibrium binding constant K ₁₁, which value increases as the length of alkyl chains, and consequently the hydrophobicity, increases. From mathematical model the concentrations of the uncomplexed cyclodextrin, uncomplexed surfactant ion, and inclusion complex in the submicellar, as well as in the micellar range were calculated. The competition between the micellization and complexation processes leads to the existence of a significant concentration of free CD in equilibrium with the micellar aggregates. The percentage of uncomplexed cyclodextrin in equilibrium with the micelles is independent on cyclodextrin concentration for a particular ternary system and is 31, 37, and 34 % for C₁₂TAB/water/ß-CD, C₁₄TAB/water/ß-CD and C₁₆TAB/water/ß-CD, respectively. By using standard Gibbs free energy for micellization and surfactant complexation by CD, we can explain the observed behavior.     

Free-energy calculations of the host–guest association in grafted supramolecular assemblies

Herein, we investigate the impact of grafting macrocyclic hosts with hydrophobic cavities onto a gold surface on the association with a guest molecule of particular importance to applications for molecular machines. We establish that the increase of the grafted alkyl chain length and number of anchor points strengthens the binding of the guest with the β-cyclodextrin host. This is the opposite effect with the p-sulfonatocalix[4]arene host for which the grafting considerably reduces the strength of the host–guest association. The structural and thermodynamic characterizations, carried out with free energy simulations, are combined to rationalize the differences in the association process in both heterogeneous and homogeneous conditions.     

Needle-like supramolecular amphiphilic assembly constructed by the host–guest interaction between calixpyridinium and methotrexate disodium

In this work, the host–guest interaction between calixpyridinium and the anionic anticancer drug methotrexate disodium was explored in water. Unexpectedly, an interesting anisotropic needle-like rather than an ordinary isotropic spherical supramolecular amphiphilic assembly was fabricated by the complexation of calixpyridinium with methotrexate disodium. It is the second anionic guest to be discovered to form the non-spherical supramolecular assembly upon complexation with calixpyridinium. This discovery implies the possibility to construct various topological nanostructures based on the host–guest interactions between calixpyridinium and the anionic drugs in the future. The resulting calixpyridinium–drug assemblies with different morphologies may have the diverse potentials to adjust the efficacies of anionic drugs.     

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.     

Solid-state NMR studies of host–guest chemistry in metal-organic frameworks

Metal-organic frameworks (MOFs) are an emerging class of porous materials with potential applications in a wide variety of fields. The knowledge about the detailed interactions between MOFs and guest molecules is critical for the understanding of their structure-property relationships at working conditions. In this review, recent advances for solid-state NMR studies of host–guest chemistry of MOFs in the application fields of gaseous adsorption, chemical separation, drug delivery, chemical sensor, and heterogeneous catalysis were briefly introduced. The adsorption property and dynamic behavior of adsorbed gases confined inside the MOFs channels were elucidated from variable-temperature (VT) solid-state NMR. Moreover, the detailed mechanism of gas-phase and liquid-phase adsorptive separations on MOFs adsorbents was uncovered on the basis of solid-state NMR measurements. Multi-nuclear ¹H, ¹³C, ¹⁵N, and ³¹P MAS NMR was utilized to explore the interactions between drug molecules and MOFs at the atomic scale to monitor the controlled release process of drugs. Furthermore, the investigation of the interactions between guest molecules and MOFs in the application areas of chemical sensor, toxic chemicals removal, and catalysis using solid-state NMR was briefly discussed as well.     

The formation of host–guest complexes between surfactants and cyclodextrins

Cyclodextrins are able to act as host molecules in supramolecular chemistry with applications ranging from pharmaceutics to detergency. Among guest molecules surfactants play an important role with both fundamental and practical applications. The formation of cyclodextrin/surfactant host–guest compounds leads to an increase in the critical micelle concentration and in the solubility of surfactants. The possibility of changing the balance between several intermolecular forces, and thus allowing the study of, e.g., dehydration and steric hindrance effects upon association, makes surfactants ideal guest molecules for fundamental studies. Therefore, these systems allow for obtaining a deep insight into the host–guest association mechanism. In this paper, we review the influence on the thermodynamic properties of CD–surfactant association by highlighting the effect of different surfactant architectures (single tail, double-tailed, gemini and bolaform), with special emphasis on cationic surfactants. This is complemented with an assessment of the most common analytical techniques used to follow the association process. The applied methods for computation of the association stoichiometry and stability constants are also reviewed and discussed; this is an important point since there are significant discrepancies and scattered data for similar systems in the literature.     

Supramolecular end-group separation of linear polymers with different terminals through host–guest interaction

By increasing the hydrophobicity of end group, the complexation rate between α-cyclodextrin (α-CD) and poly(ethylene glycol) (PEG) derivative speeds up greatly. Based on such a huge difference of complexation kinetics, the PEG derivative with palmityloxy terminal (PEG-C16) can be successfully separated from a carboxylic acid end-functionalized analogue (PEG-COOH) by once supramolecular purification. Adding α-CD into the aqueous solution of PEG-C16/PEG-COOH mixture, PEG-C16 is encapsulated into α-CD cavity to form the crystalline inclusion complex in a very short time, while almost all of PEG-COOH molecules are still reserved in the aqueous solution. After dichloromethane extraction, the pure PEG-C16 is obtained. Moreover, the host CD can be recycled. Thus, it is an efficient green way to separate and purify the linear polymers with different terminal functionality.     

Interconversion of host–guest components in supramolecular assemblies of polycarboxylic acids and reduced Schiff bases

Eight supramolecular assemblies of benzene-1,3,5-tricarboxylic acid (H₃BTC) and benzene-1,2,4,5-tetracarboxylic acid (H₄BTtC) with reduced Schiff base of flexible backbone having phenolic and pyridyl groups, i.e., 1,2-bis(2-hydroxybenzylamino)ethane, 1,3-bis(2-hydroxybenzylamino)propane, 1,4-bis(2-hydroxybenzylamino)butane and 1,4-bis(4-pyridinylmethylamino)butane have been constructed by proton transfer reaction. H₃BTC forms host–guest type assemblies with amines having phenolic functionality, while a layered structure was obtained with pyridyl functionalized amine. H₄BTtC also formed host–guest assemblies with the diamines where reduced Schiff base acts as host and acid moiety acts as the guest. Different conformations of the diamines were observed in these assemblies. Theoretical studies were performed to analyze the effect of varied chain lengths of diamines on hydrogen bond interaction energy of the adducts.     

Supramolecular architectures of metal–organic host–guest compounds

Metal?Corganic frameworks are a class of materials with new and interesting properties (Angew Chem Int Ed 43:2334, 2004; Coorg Chem Rev 38:1213, 2009; Adv Mater 23:249, 2011). In particular, porous metal organic systems are attracting considerable interest because of their potential use as sensors, catalysts and, in general, in host?Cguest chemistry (Acc Chem Res 43:1115, 2010). The so-called ??wheel and axle?? compounds play an important role in the developing of supramolecular chemistry and there are a lot of studies dealing with their inclusion properties and host?Cguest chemistry (Comprehensive supramolecular chemistry, 1996). Classical ??wheel and axle?? molecules have a long, thin, central part (the axle) with two bulky ends (the wheels). Here, new compounds with host properties are described, that we called ??wheel and axle metal?Corganic?? diols (WAMOD), that are decorated with OH groups in the wheel. In particular, their clathration properties are discussed in connection with their crystal structures. A modular strategy is applied to obtain WAMODs: coordination chemistry is used together with soft interactions (H-bond, ?ШC?? interaction), with the aim to realize a dynamic framework that is able to reversibly capture and release a guest. The coordination bond is robust and permits to obtain WAMODs with different arrangements of the axle; the hydrogen bonds and/or the other soft interactions are responsible for the thin adjustments in the crystal packing that allow reversible adsorption/desorption of the guest.     

HPLC study of the host–guest complexation between fluorescent glutathione derivatives and β-cyclodextrin

RP-HPLC and the van’t Hoff law were used to study the association in which β-cyclodextrin forms inclusion complexes with aminothiol–phthaldialdehyde derivatives prepared from either glutathione (GSH) or γ-glutamylcysteine (γ-glucys) and either naphthalene-2,3-dicarboxaldehyde (NDA) or o-phthaldialdehyde (OPA). Elution was carried out at pH 8.5, the derivatization pH which gave the highest fluorescence signal during batch experiments. The variation of the retention factor (k) was monitored as a function of column temperature (10–35 °C) and β-cyclodextrin concentration (0–5 mM) in the mobile phase. Apparent binding constants, enthalpy and entropy were calculated from van’t Hoff plots for the complexation reaction. These data lay the groundwork for the improvement of high throughput GSH quantification methods using fluorimetry in biological and vegetal samples.     

Synthesis of a hexacationic cyclophane and formation of EDA-type host–guest complexes

A polycationic cyclophane with six cationic sites (three 4,4′-bipyridinium cation units) supported by a rigid cyclic skeleton was synthesized. It formed electron donor–acceptor complexes with electron-rich compounds, and their inclusion properties with pyrene and calixresorcin[4]arene were studied.     

Overview of the SAMPL6 host–guest binding affinity prediction challenge

Accurately predicting the binding affinities of small organic molecules to biological macromolecules can greatly accelerate drug discovery by reducing the number of compounds that must be synthesized to realize desired potency and selectivity goals. Unfortunately, the process of assessing the accuracy of current computational approaches to affinity prediction against binding data to biological macromolecules is frustrated by several challenges, such as slow conformational dynamics, multiple titratable groups, and the lack of high-quality blinded datasets. Over the last several SAMPL blind challenge exercises, host–guest systems have emerged as a practical and effective way to circumvent these challenges in assessing the predictive performance of current-generation quantitative modeling tools, while still providing systems capable of possessing tight binding affinities. Here, we present an overview of the SAMPL6 host–guest binding affinity prediction challenge, which featured three supramolecular hosts: octa-acid (OA), the closely related tetra-endo-methyl-octa-acid (TEMOA), and cucurbit[8]uril (CB8), along with 21 small organic guest molecules. A total of 119 entries were received from ten participating groups employing a variety of methods that spanned from electronic structure and movable type calculations in implicit solvent to alchemical and potential of mean force strategies using empirical force fields with explicit solvent models. While empirical models tended to obtain better performance than first-principle methods, it was not possible to identify a single approach that consistently provided superior results across all host–guest systems and statistical metrics. Moreover, the accuracy of the methodologies generally displayed a substantial dependence on the system considered, emphasizing the need for host diversity in blind evaluations. Several entries exploited previous experimental measurements of similar host–guest systems in an effort to improve their physical-based predictions via some manner of rudimentary machine learning; while this strategy succeeded in reducing systematic errors, it did not correspond to an improvement in statistical correlation. Comparison to previous rounds of the host–guest binding free energy challenge highlights an overall improvement in the correlation obtained by the affinity predictions for OA and TEMOA systems, but a surprising lack of improvement regarding root mean square error over the past several challenge rounds. The data suggests that further refinement of force field parameters, as well as improved treatment of chemical effects (e.g., buffer salt conditions, protonation states), may be required to further enhance predictive accuracy.     

Host–guest system of Vitamin B10 in β-cyclodextrin: characterization of the interaction in solution and in solid state

Conventional drugs are usually formulated for the immediate release of the medicinal substances and for obtaining the desired therapeutic effect. The aim of this paper was to investigate the possible interactions between Vitamin B10 and β-cyclodextrin (β-CD), to determine the physical-chemical characteristics and the interactions present in the corresponding inclusion compound. The so-obtained compounds were characterized by X-ray diffraction, DSC and FTIR spectroscopy. ¹H NMR and UV–vis spectroscopic methods were employed to study the inclusion process in aqueous solution. The X-ray powder diffraction patterns demonstrate the inclusion compound formation, especially for the lyophilized product where the amorphous phase dominates. The existence of the inclusion compounds obtained by different methods was confirmed by comparing with DSC and FTIR data of the pure compounds and the (1:1) Vitamin B10:β-CD physical mixture (pm). ¹H NMR measurements on aqueous solutions of Vitamin B10 and β-CD in D₂O allowed us to establish the corresponding Vitamin B10’s and cyclodextrin’s protons implied in the complexation process. 2D NMR spectroscopy established the geometry of the inclusion complex. ¹H NMR, UV–Vis and fluorescence data were used to obtain the stoichiometry and the stability constant of the complex.     

Complexes of TETROL with selected heterocyclics: unconventional host–guest hydrogen bonding and the correlation with host selectivity

Here we investigate and compare the more salient characteristics of host–guest complexes of (+)-(2R,3R)-1,1-4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) with four heterocyclic guests, morpholine, piperidine, pyridine and dioxane. These guests each formed inclusion compounds with TETROL, and host:guest ratios were either 1:2 or 1:1. Single crystal diffraction experiments revealed unprecedented host behaviour in the presence of both piperidine and dioxane with respect to the mode of host–guest hydrogen bonding employed. Furthermore, by utilizing ¹H-NMR spectroscopy or gas chromatography (as applicable) as methods for analysing complexes obtained from competition experiments, we were able to identify the host selectivity order, and were gratified to discover that this order correlated precisely with host–guest hydrogen bond distance.     

Cooperative binding of an anticancer drug in a guest–host–protein assembly

The supramolecular formation of an anticancer drug (6-mercaptopurine (6-MP)) in an acetate buffer solution was demonstrated through a host–guest interaction with the macrocyclic host cucurbit[7]uril (Q[7]) and bovine serum albumin (BSA). With the help of ultraviolet absorption and fluorescence spectroscopy, it was shown that a binary complex formed between 6-MP and Q[7] and/or BSA, and a specific binding interaction took place between 6-MP and Q[7] in the presence of BSA. The inclusion constants and thermodynamic parameters were determined at different temperatures. The data suggested that the formation of the binary 6-MP–Q[7] complex was driven by enthalpy in the presence of an unfavourable entropy, which was attributed to the van der Waals and hydrophobic interactions. The fluorescence quenching of BSA by 6-MP was a result of the formation of the 6-MP–BSA complex. This quenching occurred by a static quenching mechanism, and hydrophobic forces played predominant roles in the binding process. Moreover, the absorption data suggested that the interaction between 6-MP and Q[7] or BSA was a competitive process. In addition, the effect of 6-MP on BSA conformation was investigated by synchronous and 3D fluorescence spectra.     

Testing the effect of the cavity size and the number of molecular substitutions in host–guest complexes formed by 2-hydroxypropyl-cyclodextrins and n-octyl-β-d-glucopyranoside

The thermodynamic characterization of host–guest complex formation processes based on modified cyclodextrins (CDs) presents several difficulties that are absent when using native CDs. They are mainly due to the relatively wide distribution of the degree of molecular substitution and also to the indeterminacy in the location of the modified groups. A more common trouble would arise from the coexistence of coupled processes, such as CD-surfactant complexation and surfactant demicellization. In the present work a reasonable approach based on the analysis of isothermal titration calorimetric measurements is employed to assess the effect of the number of molecular substitutions as well as of the CD cavity size in supra-molecular complexes formed by 2-hydroxypropyl-CDs and n-octyl-β-d-glucopyranoside. The employed method considers both first- (1:1) and second-order (1:2 and 2:1) stoichiometries. The results were significantly different from those previously observed for native CDs. The substituted groups increase entropically the stability of 1:1 species based on α-CD, while compete with the surfactant for the CD cavity in the case of 1:1 and 1:2 species based on β- and γ-CD, respectively. Also, the modified β-CD seems to enhance the formation of non-inclusion second-order complexes.     

Simultaneous enhancement of phosphorescence and chirality by host–guest recognition of molecular tweezers

A novel type of host–guest recognition systems have been developed on the basis of a Au(III) molecular tweezer receptor and chiral Pt(II) guests. The complementary host–guest motifs display high non-covalent binding affinity (K_a: ～10⁴ L/mol) due to the participation of two-fold intermolecular π–π stacking interactions. Both phosphorescence and chirality signals of the Pt(II) guests strengthen in the resulting host–guest complexes, because of the cooperative rigidifying and shielding effects rendered by the tweezer receptor. Their intensities can be reversibly switched toward pH changes, by taking advantage of the electronic repulsion effect between the protonated form of tweezer receptor and the positive-charged guests in acidic environments. Overall, the current study demonstrates the feasibility to enhance and modulate phosphorescence and chirality signals simultaneously via molecular tweezer-based host–guest recognition.     

Physicochemical characterization and molecular modeling study of host–guest systems of aripiprazole and functionalized cyclodextrins

Journal of Thermal Analysis and Calorimetry - Aripiprazole (ARP), an innovative atypical antipsychotic drug, exhibits very low aqueous solubility, affecting its dissolution and absorption and high...     

Characterisation of azo dye and carbon nanoparticle-doped guest–host liquid crystalline matrix

During the recent years, liquid crystals (LCs) have much attention owing to their wide range of possible application and structural properties in electronics and optics. In this study, two different azo structured dyes (Disperse Yellow 3 and 7) and their mixture were separately doped to each of two different nematic LCs (E8 and E63). Their solubilities (except dye mixture), order parameters, textures and phase transition temperatures were determined. Single-walled nanotubes and fullerene C60 in a small amount were separately added to each of these solutions, and the experiments were repeated at the final stage analogously except solubilities. The solubilities of dyes in the LC E63 were lower than those of E8. The highest order parameter value was attained with Yellow 7 dye in E63 nematic host.