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.     

Electrospray‐Ionization Mass Spectrometry for Screening the Specificity and Stability of Single‐Stranded‐DNA Templated Self‐Assemblies

Supramolecular complexes consisting of a single‐stranded oligothymine ( dTn ) as the host template and an array of guest molecules equipped with a complementary diaminotriazine hydrogen‐bonding unit have been studied with electrospray‐ionization mass spectrometry (ESI‐MS). In this hybrid construct, a supramolecular stack of guest molecules is hydrogen bonded to dTn . By changing the hydrogen‐bonding motif of the DNA host template or the guest molecules, selective hydrogen bonding was proven. We were able to detect single‐stranded‐DNA (ssDNA)–guest complexes for strands with lengths of up to 20 bases, in which the highest complex mass detected was 15 kDa; these complexes constitute 20‐component self‐assembled objects. Gas‐phase breakdown experiments on single‐ and multiple‐guest–DNA assemblies gave qualitative information on the fragmentation pathways and the relative complex stabilities. We found that the guest molecules are removed from the template one by one in a highly controlled way. The stabilities of the complexes depend mainly on the molecular weight of the guest molecules, a fact suggesting that the complexes collapse in the gas phase. By mixing two different guests with the ssDNA template, a multicomponent dynamic library can be created. Our results demonstrate that ESI‐MS is a powerful tool to analyze supramolecular ssDNA complexes in great detail.     

Cucurbiturils–a New Family of Host Molecules

The supramolecular chemistry of cucurbituril, a synthetic receptor, is fascinating because of the remarkable guest binding behavior of the host. Although cucurbituril is potentially as useful as crown ethers, cyclodextrins, and calixarenes in many applications, its chemistry has not been developed much until recently because of several shortcomings. Recently we synthesized cucurbituril homologues and derivatives. These new members of the cucurbituril family have expanded the scope further, and interest in them has grown enormously. The diversity in guest binding behavior has led to many interesting studies such as redox control of guest binding, stabilization of charge-transfer complexes inside the host cavity, encapsulation of drug molecules, formation of redox-controllable vesicles, and so on. The cucurbituril homologues and derivatives thus provide new opportunities in many areas of supramolecular chemistry including recognition, catalysis, separation, transport, and many others.     

Complexation with diol host compounds. Part 18. Structures and thermal analysis of trans-9,10-dihydroxy-9,10-di-p-tolyl-9,10-dihydroanthracene and its inclusion compounds with acetone,diethyl ether and pyridine

Abstract

The structure of the host compound trans-9,10-dihydroxy-9,10-di-p-tolyl-9,10-dihydroanthracene and those of its inclusion compounds with acetone, diethyl ether and pyridine have been elucidated. The non-porous α-phase of the host has a structure in which the molecules are packed in layers parallel to the (100) plane, but exhibit no intermolecular hydrogen bonding. The host:guest stoichiometry of each inclusion compound is 1:2, and the structures are each stabilised by O-H…O or O-H…N hydrogen bonds between host and guest. The thermal decompositions of the acetone and diethyl ether compounds are characterised by single endotherms of the guest-release reaction, but the pyridine inclusion compound has a more complex decomposition, characteristic of similar pyridine inclusion compounds.     

CH/π, CH/O弱氢键在2,6-二(α-苯基苄基)-1,5-萘二酚主体分子包结物构筑中的作用

设计、合成了一种新的主体分子2,6-二(α-苯基苄基)-1,5-萘二酚 (1). 它可与许多有机小分子形成配位包合物. 用IR和¹H NMR表征了配位包结物, 并测定了主客体分子的摩尔比: 1•DMF (1∶1), 1•DMSO (1∶2), 1•吡啶 (1∶1), 1•喹啉(1∶2), 1•N-甲基吡咯烷酮(1∶1). 用单晶X衍射分析了包结物 (1)•DMF的晶体结构, 属三斜晶系, 晶胞参数为P-1, a＝0.9085(9) nm, b＝0.9501(6) nm, c＝2.0995(6) nm, α＝99.59(3)°, β＝90.13(4)°, γ＝96.20(7)°, V＝1.776(2) nm³, D_c＝1.898 g•cm^－3. 结果表明, 主体分子间的CH/π弱氢键在决定主体分子的层状框架结构和客体分子在层间的填充方式中发挥了重要作用; 两种不等效的客体分子与主体分子的作用方式是不同的, 一种客体分子是通过CH/π, CH/O弱氢键与同层的不同主体分子相互作用, 另一种是通过CH/π, CH/O弱氢键与相邻层的不同主体分子相互作用.     

Amphiphilic Inclusion Spaces for Various Guests and Regulation of Fluorescence Intensity of 1,8‐Bis(4‐aminophenyl)anthracene Crystals

A host framework for inclusion of various guest molecules was investigated by preparation of inclusion crystals of 1,8‐bis(4‐aminophenyl)anthracene (1,8‐BAPA) with organic solvents. X‐ray crystallographic analysis revealed construction of the same inclusion space incorporating 1,8‐BAPA and eight guest molecules including both non‐polar (benzene) and polar guests (N,N‐dimethylformamide, DMF). Fluorescence efficiencies varied depending on guest molecule polarity; DMF inclusion crystals exhibited the highest fluorescence intensity (Φ_F=0.40), four times as high as that of a benzene inclusion crystal (Φ_F=0.10). According to systematic investigations of inclusion phenomena, strong host–guest interactions and filling of the inclusion space led to a high fluorescence intensity. Temperature‐dependent fluorescence spectral measurements revealed these factors effectively immobilised the host framework. Although hydrogen bonding commonly decreases fluorescence intensity, the present study demonstrated that such strong interactions provide excellent conditions for fluorescence enhancement. Thus, this remarkable behaviour has potential application toward sensing of highly polar molecules, such as biogenic compounds.     

Space filling of permethylated β‐cyclodextrin by volatile hydrophobic and hydrophilic guests in polyethylene glycol

The inclusion of volatile organic compounds of various classes in the permethylated β‐cyclodextrin in an oligomeric solution of polyethylene glycol was investigated by inverse gas–liquid chromatography methods and by a stereochemical approach. It was established that the “guest–host” complexation process is influenced by the geometrical structure of the guest molecules, their chirality, and entropy factors.     

Elucidating the mechanism of binding of chromate to cucurbit[6]uril: a DFT study

We report the binding of chromate, a toxic heavy metal ion to the macrocyclic host molecule, cucurbituril using density functional theory. Due to the anionic nature of the guest molecule and the portals of the host molecule, we propose that the binding mechanism should be assisted by cations. The calculated barrier for chromate binding to cucurbituril is found to be?~17?kcal?mol^?1. The large barrier can be attributed to portal opening of the host molecule, electrostatic repulsion between the guest molecule and the portals of the host molecule and the solvent re-organization around guest molecule.     

"Venetian blinds" mechanism of solvation/desolvation in palladium(II) wheel-and-axle organic-inorganic diols

A family of organic-inorganic wheel-and-axle diols (Pd(LOH)(2)Cl(2), Pd(LOH)(2)(CH(3))Cl, Pd(LOH)(2)(CH(3)COO)(2), LOH = alpha-(4-pyridyl)benzhydrol) and several corresponding solvates are synthesized and characterized by single-crystal X-ray diffraction analysis. Their structures are compared to investigate the factors governing the modes of solid state association, the propensity to clathration, and the structural basis of guest inclusion. In all the complexes, the palladium coordination is a slightly distorted square. The LOH ligands coordinate Pd(2+) by means of the 4-pyridyl ring. In the chloride complexes solvation occurs with a 1:2 host/guest ratio by hydrogen bonding between the terminal -OH groups of the complex diol and one acceptor atom on the guest, and it is further assisted by guest stacking between host aryl rings. All solvates are organized in layers with practically invariant metrics, while the layers may be assembled in different arrangements. The structures of the nonsolvate compounds are related to the metrics of the solvate forms by rotation of the complex molecules within the layer plane. In all cases the nonsolvates are completely converted into the corresponding crystalline solvate forms by exposure to the vapor of the guest, and conversely they are quantitatively recovered from the solvate upon removal of the guest by mild conditions. On the basis of the structural data, it is proposed that the solvation/desolvation process proceeds by a concerted rotation of the complex molecules in the layer plane. The structural analysis of Pd(LOH)(2)(CH(3)COO)(2) and of its tetrahydrofuran monosolvate form suggests that the first step of the solid/gas solvation process may imply the clathration of 1 mol of guest between the aryl rings, which successively triggers the collective reorientation of the host molecules.     

Effects of several inter-molecular interactions on the inclusion between methyl substituted β-cyclodextrin and some linear macromolecule in supercritical carbon dioxide medium

In this work, the inclusion between methyl substitute β-cyclodextrin and some linear macromolecule in supercritical carbon dioxide medium was investigated. The contributions from several factors were studied; such as the hydrogen bonding interaction between the host and guest, the hydrogen bonding interaction between the neighborhood cyclodextrin rims threaded on the polymer chain, and the matching between the host cavity and the size of the polymer axis.     

Supramolecular Assemblies of (±-2,2''''-Dihydroxy-1,1''''-binaphthyl with 2,2''''-Bipyridine and Naphthodiazine

Introduction Optically active 1,1'-bi-2-naphthol (BINOL) and its derivatives have been widely used as chiral ligands of catalysts for asymmetric reactions and effective host compounds for the isolation or optical resolution of a wide range of organic guest molecules through the for-mation of crystalline inclusion complexes.1,2 The wide-ranging and important applications of these com-pounds in organic synthesis have stimulated great inter-est in developing efficient methods for their prepara-…     

Recognition of N‐Alkyl and N‐Aryl Acetamides by N‐Alkyl Ammonium Resorcinarene Chlorides

N‐Alkyl ammonium resorcinarene chlorides are stabilized by an intricate array of intra‐ and intermolecular hydrogen bonds that leads to cavitand‐like structures. Depending on the upper‐rim substituents, self‐inclusion was observed in solution and in the solid state. The self‐inclusion can be disrupted at higher temperatures, whereas in the presence of small guests the self‐included dimers spontaneously reorganize to 1:1 host–guest complexes. These host compounds show an interesting ability to bind a series of N‐alkyl acetamide guests through intermolecular hydrogen bonds involving the carbonyl oxygen (C?O) atoms and the amide (NH) groups of the guests, the chloride anions (Cl^?) and ammonium (NH₂⁺) cations of the hosts, and also through CH ??? π interactions between the hosts and guests. The self‐included and host–guest complexes were studied by single‐crystal X‐ray diffraction, NMR titration, and mass spectrometry.     

Molecular recognition of naphthalenediamine by polyamine modified β-cyclodextrin:yttrium metal complexes

The 6-OH group of β-cyclodextrin was modified by diethylene triamine and triethylene tetramine, respectively, mono[6-diethylenetriamino]-6-deoxy-β-cyclodextrin (DTCD) and mono[6-triethylenetetraamino]-6-deoxy-β-cyclodextrin (TTCD) were synthesized, which included 1,5-naphthalenediamine and 1,8-naphthalenediamine, respectively, in the presence of rare earth metal yttrium chloride. As a result, four ternary inclusion complexes (host–guest-metal) formed, which were characterized via ¹HNMR spectroscopy. The chemical shift variations of host and guest molecules were studied. The stoichiometric proportion of host and guest molecules is 2:1 for all the complexes. Signal degeneration still exists for the guest molecules after the inclusion process, which verifies the symmetrical conformation of guest molecules inside the cavities of two host molecules. All the four complexes exhibit “sandwich”-typed structure.     

Hydrogen bonding of excited states in supramolecular host-guest inclusion complexes

Host-guest inclusion complexes represent an important type of supramolecular structure, one which finds widespread applications in diverse areas including separations science, the food industry, molecular sensors and optical devices. There are several driving forces for the formation of such inclusion complexes in solution; one of the most important is hydrogen bonding between the guest and host molecules. The nature or strength of the hydrogen bonding may change upon electronic excitation of the guest, for example during fluorescence studies or when the inclusion complex is used as an optical sensor. In this Perspective article, the impact of hydrogen bonding between excited state guests and their hosts is examined in detail, in terms of the impact on the formation and stability of such excited state complexes, the effects on guest fluorescence, changes in the stability of ground state guest complexes upon electronic excitation, the application of inclusion complexes as fluorescent sensors and materials, and the use of fluorescence spectroscopy for their study.     

Synthesis and X-ray structure of the inclusion complex of dodecamethylcucurbit[6]uril with 1,4-dihydroxybenzene

The synthesis, and X-ray crystal structure of the inclusion host-guest complex of dodecamethylcucurbit[6]uril (DDMeQ[6]) with 1,4-dihydroxybenzene (DHOBEN) are reported. The complex crystallizes in the space group P21/c (No.14) with a =12.2847(4), b = 12.6895(4), c = 15.1310(4) A, alpha = 74.6960(10), beta = 71.4090(10), gamma = 86.5090(10) degrees and Z = 1. A novel approach to dodecamethylcucurbit[6]uril synthesis is also described. To separate dodecamethylcucurbit[6]uril, 1,4-dihydroxybenzene is used as a guest molecule for crystallization of the fully methyl-substituted cucurbituril. The driving force for the self-assembled inclusion host-guest complex can be attributed to not only the cavity interaction of dodecamethylcucurbit[6]uril (host), but also to the hydrogen bonding between the carbonyl oxygen at the portals of the host and the hydroxy groups of the guest.     

Spectroscopic Observation of the Hydroxy Position in Butanol Hydrates and Its Effect on Hydrate Stability

In this study, we investigate the crystal structures and phase equilibria of butanols+CH₄+H₂O systems to reveal the hydroxy group positioning and its effects on hydrate stability. Four clathrate hydrates formed by structural butanol isomers are identified with powder X‐ray diffraction (PXRD). In addition, Raman spectroscopy is used to analyze the guest distributions and inclusion behaviors of large alcohol molecules in these hydrate systems. The existence of a free OH indicates that guest molecules can be captured in the large cages of structure II hydrates without any hydrogen‐bonding interactions between the hydroxy group of the guests and the water‐host framework. However, Raman spectra of the binary (1‐butanol+CH₄) hydrate do not show the free OH signal, indicating that there could be possible hydrogen‐bonding interactions between the guests and hosts. We also measure the four‐phase equilibrium conditions of the butanols+CH₄+H₂O systems.     

Thermoresponsive Synergistic Hydrogen Bonding Switched by Several Guest Units in a Water‐Soluble Polymer

Thermoresponsive synergistic hydrogen bonding (H‐bonding) switched by several guest units in a water‐soluble polymer is reported. Adjusting the distribution of guest units can effectively change the synergistic H‐bonding inside polymer chains, thus widely switch the preorganization and thermoresponsive behavior of a water‐soluble polymer. The synergistic H‐bonding is also evidenced by converting less polar aldehyde groups into water‐soluble oxime groups, which bring about the lowering‐down of cloud point and an amplified hysteresis effect. This is a general approach toward the wide tunability of thermosensitivity of a water‐soluble polymer simply by adjusting the distribution of several guest H‐bonding units.     

Host Perturbation in a β‐Hydroquinone Clathrate Studied by Combined X‐ray/Neutron Charge‐Density Analysis: Implications for Molecular Inclusion in Supramolecular Entities

X‐ray/neutron (X/N) diffraction data measured at very low temperature (15 K) in conjunction with ab initio theoretical calculations were used to model the crystal charge density (CD) of the host–guest complex of hydroquinone (HQ) and acetonitrile. Due to pseudosymmetry, information about the ordering of the acetonitrile molecules within the HQ cavities is present only in almost extinct, very weak diffraction data, which cannot be measured with sufficient accuracy even by using the brightest X‐ray and neutron sources available, and the CD model of the guest molecule was ultimately based on theoretical calculations. On the other hand, the CD of the HQ host structure is well determined by the experimental data. The neutron diffraction data provide hydrogen anisotropic thermal parameters and positions, which are important to obtain a reliable CD for this light‐atom‐only crystal. Atomic displacement parameters obtained independently from the X‐ray and neutron diffraction data show excellent agreement with a |ΔU| value of 0.00058 Ų indicating outstanding data quality. The CD and especially the derived electrostatic properties clearly reveal increased polarization of the HQ molecules in the host–guest complex compared with the HQ molecules in the empty HQ apohost crystal structure. It was found that the origin of the increased polarization is inclusion of the acetonitrile molecule, whereas the change in geometry of the HQ host structure following inclusion of the guest has very little effect on the electrostatic potential. The fact that guest inclusion has a profound effect on the electrostatic potential suggests that nonpolarizable force fields may be unsuitable for molecular dynamics simulations of host–guest interaction (e.g., in protein–drug complexes), at least for polar molecules.     

Three polymorphs of an inclusion compound of 2,2′‐(disulfanediyl)dibenzoic acid and trimethylamine

Polymorphism is the ability of a solid material to exist in more than one form or crystal structure and this is of interest in the fields of crystal engineering and solid‐state chemistry. 2,2′‐(Disulfanediyl)dibenzoic acid (also called 2,2′‐dithiosalicylic acid, DTSA) is able to form different hydrogen bonds using its carboxyl groups. The central bridging S atoms allow the two terminal arene rings to rotate freely to generate various hydrogen‐bonded linking modes. DTSA can act as a potential host molecule with suitable guest molecules to develop new inclusion compounds. We report here the crystal structures of three new polymorphs of the inclusion compound of DTSA and trimethylamine, namely trimethylazanium 2‐[(2‐carboxyphenyl)disulfanyl]benzoate 2,2′‐(disulfanediyl)dibenzoic acid monosolvate, C₃H₁₀N⁺·C₁₄H₉O₄S₂⁻·C₁₄H₁₀O₄S₂, (1), tetrakis(trimethylazanium) bis{2‐[(2‐carboxyphenyl)disulfanyl]benzoate} 2,2′‐(disulfanediyl)dibenzoate 2,2′‐(disulfanediyl)dibenzoic acid monosolvate, 4C₃H₁₀N⁺·2C₁₄H₉O₄S₂⁻·C₁₄H₈O₄S₂²⁻·C₁₄H₁₀O₄S₂, (2), and trimethylazanium 2‐[(2‐carboxyphenyl)disulfanyl]benzoate, C₃H₁₀N⁺·C₁₄H₉O₄S₂⁻, (3). In the three polymorphs, DTSA utilizes its carboxyl groups to form conventional O—H…O hydrogen bonds to generate different host lattices. The central N atoms of the guest amine molecules accept H atoms from DTSA molecules to give the corresponding cations, which act as counter‐ions to produce the stable crystal structures via N—H…O hydrogen bonding between the host acid and the guest molecule. It is noticeable that although these three compounds are composed of the same components, the final crystal structures are totally different due to the various configurations of the host acid, the number of guest molecules and the inducer (i.e. ancillary experimental acid).     

α‐Cyclodextrin Host–Guest Binding: A Computational Study of the Different Driving Forces

Free‐energy differences govern the equilibrium between bound and unbound states of a host and its guest molecules. The understanding of the underlying entropic and enthalpic contributions, and their complex interplay are crucial for the design of new drugs and inhibitors. In this study, molecular dynamics (MD) simulations were performed with inclusion complexes of α‐cyclodextrin (αCD) and three monosubstituted benzene derivatives to investigate host–guest binding. αCD Complexes are an ideal model system, which is experimentally and computationally well‐known. Thermodynamic integration (TI) simulations were carried out under various conditions for the free ligands in solution and bound to αCD. The two possible orientations of the ligand inside the cavity were investigated. Agreement with experimental data was only found for the more stable orientation, where the substituent resides inside the cavity. The better stability of this conformation results from stronger Van der Waals interactions and a favorable antiparallel host–guest dipole–dipole alignment. To estimate the entropic contributions, simulations were performed at three different temperatures (250, 300, and 350 K) and using positional restraints for the host. The system was found to be insensitive to both factors, due to the large and symmetric cavity of αCD, and the nondirectional nature of the host–guest interactions.