Functioning via host–guest interactions

Molecular recognition is essential for realizing functional supramolecular materials. Non-covalent host–guest interactions are an effective tool to introduce switching and functional properties into materials. This review focuses on the achievement of selective molecular adhesion, self-healing, toughness, and actuation properties. These functions have been achieved by reversible bond formation with cyclodextrins (CDs). Self-healing materials with host–guest interactions involving CDs have been used to achieve redox-responsive healing properties and healing efficiency. Furthermore, the materials, which undergo self-healing by chemical and physical mechanisms, exhibit rapid and efficient self-healing properties under semi-dry conditions. To prepare a supramolecular actuator using host–guest complexes, two approaches have been introduced. The first is the functionalization of a supramolecular gel actuator by changing the cross-linking density, and the second is the functionalization of a topological gel actuator by changing distances between the cross-linking points. Both actuators exhibit contractive bending behavior. This review summarizes advancements within the past ten years in supramolecular materials that function via the chemical mechanism of host–guest interactions and the physical mechanism of the sliding motion of ring molecules.     

Lyotropic liquid crystal guest–host material and anisotropic thin films for optical applications

We propose a new approach for the production of thin film optical functional materials. The method is based on molecular design whereby two different types of lyotropic liquid crystals (LC), lyotropic LC based on columnar supramolecules and water-soluble rod-like polymer molecules are mixed. The resulting lyotropic guest–host system allows production of optical retardation films with tunable optical anisotropy controlled by composition of the guest–host system. Coatable retarders can be used in modern liquid crystal displays and TVs for optical compensation and enhancement of the LCD's performance.     

Stimuli-responsive polymeric materials functioning via host–guest interactions

Molecular recognition is essential for realizing functional supramolecular materials. Non-covalent host–guest interactions are an effective tool to introduce switching and functional properties into materials. This review focuses on the achievement of selective molecular adhesion, self-healing, toughness, and actuation properties. These functions have been achieved by reversible bond formation with cyclodextrins (CDs). Self-healing materials with host–guest interactions involving CDs have been used to achieve redox-responsive healing properties and healing efficiency. Furthermore, the materials, which undergo self-healing by chemical and physical mechanisms, exhibit rapid and efficient self-healing properties under semi-dry conditions. To prepare a supramolecular actuator using host–guest complexes, two approaches have been introduced. The first is the functionalization of a supramolecular gel actuator by changing the cross-linking density, and the second is the functionalization of a topological gel actuator by changing distances between the cross-linking points. Both actuators exhibit contractive bending behavior. This review summarizes advancements within the past 10 years in supramolecular materials that function via the chemical mechanism of host–guest interactions and the physical mechanism of the sliding motion of ring molecules.     

Enhanced ordering in polymer stabilised ferroelectric liquid crystal guest–host composites: evidence by polarised fluorescence spectroscopy

Guest–host polymer stabilised ferroelectric liquid crystal (PSFLC) composite films have been prepared by polymerisation-induced phase separation process. A small quantity (0.1, 0.25 and 0.5 wt %) of anthraquinone dye in PSFLC host matrix was homogeneously dispersed to create molecular ordering in fibrils network of guest–host composite film. Ordered twisted fibril morphology was clearly observed through optical polarising microscope and thus we determined the order parameter from the dichroism measurements with the help of polarised fluorescence spectroscopy, which impacts the significant contribution of dye molecules into the smectic layers of the host polymer stabilised ferroelectric matrix.     

SAMPL6 host–guest challenge: binding free energies via a multistep approach

In this effort in the SAMPL6 host–guest binding challenge, a combination of molecular dynamics and quantum mechanical methods were used to blindly predict the host–guest binding free energies of a series of cucurbit[8]uril (CB8), octa-acid (OA), and tetramethyl octa-acid (TEMOA) hosts bound to various guest molecules in aqueous solution. Poses for host–guest systems were generated via molecular dynamics (MD) simulations and clustering analyses. The binding free energies for the structures obtained via cluster analyses of MD trajectories were calculated using the MMPBSA method and density functional theory (DFT) with the inclusion of Grimme’s dispersion correction, an implicit solvation model to model the aqueous solution, and the resolution-of-the-identity (RI) approximation (MMPBSA, RI-B3PW91-D3, and RI-B3PW91, respectively). Among these three methods tested, the results for OA and TEMOA systems showed MMPBSA and RI-B3PW91-D3 methods can be used to qualitatively rank binding energies of small molecules with an overbinding by 7 and 37 kcal/mol respectively, and RI-B3PW91 gave the poorest quality results, indicating the importance of dispersion correction for the binding free energy calculations. Due to the complexity of the CB8 systems, all of the methods tested show poor correlation with the experimental results. Other quantum mechanical approaches used for the calculation of binding free energies included DFT without the RI approximation, utilizing truncated basis sets to reduce the computational cost (memory, disk space, CPU time), and a corrected dielectric constant to account for ionic strength within the implicit solvation model.     

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.     

The SAMPL4 host–guest blind prediction challenge: an overview

Prospective validation of methods for computing binding affinities can help assess their predictive power and thus set reasonable expectations for their performance in drug design applications. Supramolecular host–guest systems are excellent model systems for testing such affinity prediction methods, because their small size and limited conformational flexibility, relative to proteins, allows higher throughput and better numerical convergence. The SAMPL4 prediction challenge therefore included a series of host–guest systems, based on two hosts, cucurbit[7]uril and octa-acid. Binding affinities in aqueous solution were measured experimentally for a total of 23 guest molecules. Participants submitted 35 sets of computational predictions for these host–guest systems, based on methods ranging from simple docking, to extensive free energy simulations, to quantum mechanical calculations. Over half of the predictions provided better correlations with experiment than two simple null models, but most methods underperformed the null models in terms of root mean squared error and linear regression slope. Interestingly, the overall performance across all SAMPL4 submissions was similar to that for the prior SAMPL3 host–guest challenge, although the experimentalists took steps to simplify the current challenge. While some methods performed fairly consistently across both hosts, no single approach emerged as consistent top performer, and the nonsystematic nature of the various submissions made it impossible to draw definitive conclusions regarding the best choices of energy models or sampling algorithms. Salt effects emerged as an issue in the calculation of absolute binding affinities of cucurbit[7]uril-guest systems, but were not expected to affect the relative affinities significantly. Useful directions for future rounds of the challenge might involve encouraging participants to carry out some calculations that replicate each others’ studies, and to systematically explore parameter options.     

Electrochemistry and electrochemiluminescence for the host–guest system laponite–tris(2,2′-bipyridyl)ruthenium(II)

The cationic luminescence probe, tris(2,2′-bipyridyl)ruthenium(II) complex ([Ru(bpy)₃]²⁺), was incorporated into laponite-modified glassy carbon electrode (GCE) via two strategies, namely, the adsorption and intercalation methods. These two incorporation methods resulted in different microenvironment for the immobilized [Ru(bpy)₃]²⁺ within laponite as well as the different host–guest and guest–guest interactions. Herein, cyclic voltammetry and electrochemiluminescence (ECL) were innovatively performed to monitor the interactions. Tripropylamine (TPA) was used as coreactant in the electrochemical and ECL system.     

Enantioseparation of 1-(p-bromophenyl)ethanol by crystallization of host–guest complexes with permethylated β-cyclodextrin: crystal structures and mechanisms of chiral recognition

It is shown that racemic 1-(p-bromophenyl)ethanol (p-Br-PE) can be quantitatively resolved by successive recrystallizations of (1:1) supramolecular complexes formed with permethylated β-cyclodextrin (TMβ-CD). The two enantiomerically pure complexes were characterized by physical methods and their crystal structures were determined. The comparison of both inclusion geometries and packing modes in these structures revealed distinct structural features allowing the enantioseparation of the guest to be understood. Chiral discrimination mechanisms are discussed in terms of the capability of TMβ-CD to induce the formation of stereospecific host–guest complexes by simple crystallization in aqueous medium.     

Infrared spectroscopic and gravimetric studies on the cyclopropylaminemetal(II) tetracyanonickellate(II) host–aromatic guest systems

The host complexes M(Cyclopropylamine)₂Ni(CN)₄ (M = Co or Cd) have been prepared in powder form. The spectral data suggest that the structures of these compounds are similar to those of the Hofmann-type hosts. The absorption and the liberation processes of the aromatic guests (benzene, toluene, 1,2-dichlorobenzene, o-xylene, m-xylene and p-xylene) in these hosts have been examined at room temperature by gravimetric and spectroscopic measurements. The desorption of the benzene guest against time has been measured. The host structures do not change on inclusion and liberation of the guest. The host compounds have been suggested as sorbents for isomeric separations.     

Proline–calixarene thiourea host–guest complex catalyzed enantioselective aldol reactions: from nonpolar solvents to the presence of water

A proline–calix[4]arene thiourea host–guest complex catalyzed intermolecular aldol reaction of aromatic aldehydes with cyclohexanone has been developed. The anti-configured products were obtained in good yields and with high enantioselectivities. The reaction is proposed to work via a modified Houk–List model, where the carboxylate part of the proline constitutes as a supramolecular system with the thiourea. The outcome of the study indicates the influence of the calix[4]arene thiourea on both the reactivity and selectivity in a non-polar reaction medium, even in the presence of water at moderate temperatures.     

Blind prediction of host–guest binding affinities: a new SAMPL3 challenge

The computational prediction of protein-ligand binding affinities is of central interest in early-stage drug-discovery, and there is a widely recognized need for improved methods. Low molecular weight receptors and their ligands--i.e., host-guest systems--represent valuable test-beds for such affinity prediction methods, because their small size makes for fast calculations and relatively facile numerical convergence. The SAMPL3 community exercise included the first ever blind prediction challenge for host-guest binding affinities, through the incorporation of 11 new host-guest complexes. Ten participating research groups addressed this challenge with a variety of approaches. Statistical assessment indicates that, although most methods performed well at predicting some general trends in binding affinity, overall accuracy was not high, as all the methods suffered from either poor correlation or high RMS errors or both. There was no clear advantage in using explicit versus implicit solvent models, any particular force field, or any particular approach to conformational sampling. In a few cases, predictions using very similar energy models but different sampling and/or free-energy methods resulted in significantly different results. The protonation states of one host and some guest molecules emerged as key uncertainties beyond the choice of computational approach. The present results have implications for methods development and future blind prediction exercises.     

Self-assembled (pseudo)rotaxane and polyrotaxane through host–guest chemistry based on the cucurbituril family

Cucurbit[n]uril and its derivatives, a new family of macrocyclic hosts comprising n glycoluril units, have gained much attention for their exceptional application in many fields. In this review, we introduced the cucurbituril family and the development of its derivatives, which can be used in the molecular recognition and self-assembled materials such as pseudorotaxane, polyrotaxane. Moreover, cucurbituril provides the possibility to design stimulus–response devices and imitate the life secret at molecule level, such as the molecular devices controlled by pH, photochemistry, thermal and so on.     

Orientational order of guest molecules in aligned liquid crystal as measured by EPR and UV–vis techniques

Orientational order of guest molecules in aligned liquid crystal 4-cyano-4′-pentylbiphenyl (5CB) is studied via optical dichroism and electron paramagnetic resonance (EPR) spectra measurements. The guest molecules used are bifunctional molecules bearing paramagnetic nitroxide group and photochromic azobenzene moiety. The bifunctional probe with rigidly bonded nitroxide and azobenzene moieties was found to align as a whole, while flexible long spacer between the moieties provides independent alignment for the nitroxide and azobenzene parts. Intermolecular interactions responsible for the alignment of azobenzene and nitroxide moieties of the probe molecules are discussed. The molecules with cis-configuration of azobenzene moiety are able to align in the liquid-crystalline medium, but to a lesser extent than the molecules with trans-configuration. Directions of orientational axes and characteristics of rotational mobility of spin probes are determined. Second, fourth and, in some cases, sixth rank order parameter values are found.     

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.     

Overview of the SAMPL5 host–guest challenge: Are we doing better?

The ability to computationally predict protein-small molecule binding affinities with high accuracy would accelerate drug discovery and reduce its cost by eliminating rounds of trial-and-error synthesis and experimental evaluation of candidate ligands. As academic and industrial groups work toward this capability, there is an ongoing need for datasets that can be used to rigorously test new computational methods. Although protein–ligand data are clearly important for this purpose, their size and complexity make it difficult to obtain well-converged results and to troubleshoot computational methods. Host–guest systems offer a valuable alternative class of test cases, as they exemplify noncovalent molecular recognition but are far smaller and simpler. As a consequence, host–guest systems have been part of the prior two rounds of SAMPL prediction exercises, and they also figure in the present SAMPL5 round. In addition to being blinded, and thus avoiding biases that may arise in retrospective studies, the SAMPL challenges have the merit of focusing multiple researchers on a common set of molecular systems, so that methods may be compared and ideas exchanged. The present paper provides an overview of the host–guest component of SAMPL5, which centers on three different hosts, two octa-acids and a glycoluril-based molecular clip, and two different sets of guest molecules, in aqueous solution. A range of methods were applied, including electronic structure calculations with implicit solvent models; methods that combine empirical force fields with implicit solvent models; and explicit solvent free energy simulations. The most reliable methods tend to fall in the latter class, consistent with results in prior SAMPL rounds, but the level of accuracy is still below that sought for reliable computer-aided drug design. Advances in force field accuracy, modeling of protonation equilibria, electronic structure methods, and solvent models, hold promise for future improvements.     

From pharmacophore to leads: Bioactive compound discovery via computer-aided techniques

Based on the concept of Green Chemistry, a new procedure of finding bioactive compounds and their synthetic routes by computer-aided techniques was proposed. The procedure consists of pharmacophore search against a 3D structural database of natural products for lead discovery and computer-aided synthesis design for avoiding unuseful synthetic experiments. This work demonstrated that computer aided drug design and synthesis design would help us to make the consideration of environmental concerns systematically, rather than having to deal later with the unnecessary waste chemicals. Thus, it is shown that chemical computer-aided design (CAD) is an indispensable part of Green Chemistry.     

Transition metal atoms grafted on the nanodiamonds surface: Identification and guest–host spin–spin interactions

This survey describes recent achievements in creating a new type of materials – nanodiamonds grafted with atoms of transition metals. Structural features of some selected chelate complexes studied by density functional theory, their scope and limitations as well as possible applications are discussed. Using the example of copper ions, their location relative to subsurface defects of detonation diamond is investigated by the method of electron paramagnetic resonance (EPR).