Micromolar Affinity and Higher: Synthetic Host–Guest Complexes with High Stabilities

The design of high-affinity synthetic host–guest complexes is of paramount importance because they are key elements in constructing unprecedented supramolecular assemblies, functional materials, molecular probes, artificial signal transduction events, and interfaces with the biological world. The present review article collects recent achievements in the design of 1 : 1 host–guest complexes with outstanding stabilities, i.e., exceeding 10⁶ M⁻¹. The relationships between the measured thermodynamic constants and the structural parameters of the interacting species are analyzed. The design features of high-affinity hosts are discussed in light of their binding properties. Different solvents and different types of noncovalent interactions are considered for the stabilization of the complexes. Finally, some hints are provided for the design of future synthetic receptors displaying high affinity and selectivity.     

Square Grid Metal–Chloranilate Networks as Robust Host Systems for Guest Sorption

Reaction of the chloranilate dianion with Y(NO₃)₃ in the presence of Et₄N⁺ in the appropriate proportions results in the formation of (Et₄N)[Y(can)₂], which consists of anionic square-grid coordination polymer sheets with interleaved layers of counter-cations. These counter-cations, which serve as squat pillars between [Y(can)₂] sheets, lead to alignment of the square grid sheets and the subsequent generation of square channels running perpendicular to the sheets. The crystals are found to be porous and retain crystallinity following cycles of adsorption and desorption. This compound exhibits a high affinity for volatile guest molecules, which could be identified within the framework by crystallographic methods. In situ neutron powder diffraction indicates a size-shape complementarity leading to a strong interaction between host and guest for CO₂ and CH₄. Single-crystal X-ray diffraction experiments indicate significant interactions between the host framework and discrete I₂ or Br₂ molecules. A series of isostructural compounds (cat)[M^III(X-an)₂] with M=Sc, Gd, Tb, Dy, Ho, Er, Yb, Lu, Bi or In, cat=Et₄N, Me₄N and X-an=chloranilate, bromanilate or cyanochloranilate bridging ligands have been generated. The magnetic properties of representative examples (Et₄N)[Gd(can)₂] and (Et₄N)[Dy(can)₂] are reported with normal DC susceptibility but unusual AC susceptibility data noted for (Et₄N)[Gd(can)₂].     

Voltammetric Investigation of Host–Guest Systems in the Absence of a Supporting Electrolyte

Journal of Inclusion Phenomena and Macrocyclic Chemistry - In the classic voltammetric approach to host--guest systems the investigations are carried out in excess of a supporting electrolyte,...     

Electrochemical Detection of Host–Guest Interactions of Dicarboximide Pesticides with Cyclodextrins

Electrochemical methods sensitively detect the formation of host–guest complexes of cyclodextrins and three redox-active pesticides: vinclozoline (3-(3,5-dichlorophenyl)-5-methyl-5-vinyl-1,3-oxazolidine-2,4-dione), iprodione (3-(3,5-dichlorophenyl)-N-(1-methylethyl)-2,4-dioxo-1-imidazolidinecarboxamide), and procymidone (3-(3,5-dichloro-phenyl)-1,5-dimethyl-3-azabicyclo[3.1.0]hexane-2,4-dione). The protecting environment of the CD cavity allows a four-electron heterogeneous reaction leading to a preferential cleavage of the C–Cl bonds and conservation of the heterocycle structure for a further second electron transfer step. This interpretation is supported by numerical simulation of the voltammetric curves and by quantum-chemical calculations of the LUMO changes of vinclozoline. Electrochemical detection of these host–guest interactions is far superior to the spectral methods.     

Structural Analysis of Host–Guest Systems. Methyl-substituted Phenols in beta;-Cyclodextrin

Complexation trajectories and the variation ofinduced circular dichroism are calculated for thedocking of phenol and 2,4,6-trimethyl-phenol with-cyclodextrin. The results are compared toexperimental chirality data to elucidate themechanism of nonspecific molecular recognitionprocesses in aqueous solution. Large geometricalchanges along nearly isoenergetic Dynamic Monte Carlotrajectories show the conformational flexibility ofsuch host–guest systems. This proves diffuseintermolecular interactions, van der Waals orelectrostatic in nature, as the main contributions to thebinding energy. The number and position of the methylsubstituents of the guest reduces the complexityof the conformational space as the guests positionbecomes fixed by steric constraints.The solvation free energy is calculated from thesolvent accessible surface area weighted byrespective atomic solvation parameters. Consideringthe solvation term in the dynamic simulationsrestricts the conformational flexibility of themacromolecular system. The relative importance ofvarious contributions to the solvation energy isdiscussed and it is shown that those terms arisingfrom the interaction of hydrophobic groups with theaqueous environment are essential for thedetermination of the complex structure. Consideringthese terms in the dynamic simulation model, the signand strength of the calculated rotatory strength isin perfect agreement with induced circular dichroismobtained from experimentally determined averagedspectra. The results demonstrate the accuracy of thegeometrical properties of host–guest systems obtainedfrom these simulations.     

Photoregulation of Gene Expression with Amantadine-Modified Caged siRNAs through Host–Guest Interactions

RNA interference is an essential and powerful tool for targeting and verifying specific gene functions. Conditional control of small interfering RNA (siRNA) activity, especially using light activation, is a potential method for regulating target gene expression and functions. In this study, a series of photolabile siRNAs with amantadine modification have been rationally designed and developed through host–guest interactions between amantadine and β-cyclodextrin derivatives to enhance the blocking effect of siRNA binding and/or RNA-induced silencing complex processing. These caged siRNAs with amantadine modification at the 5′ end of antisense-strand RNA were efficiently inactivated through the host–guest interactions between amantadine and β-cyclodextrin. Photomodulation of the gene silencing activity of these amantadine-modified caged siRNAs targeting both exogenous and endogenous genes was successfully achieved, which indicates that host–guest interactions could be a new strategy for developing new caged siRNAs for gene photoregulation with low leaking activity.     

Regression Analysis for the Host–Guest Interaction of β-Cyclodextrin with Mono- and 1,4-Disubstituted Benzenes

A multiple regression model was generated, which can satisfactorily estimate the association constants (K _a ) for the inclusion complexation of -cyclodextrin with mono- and 1,4-disubstituted benzenes. It was found that lnK K _a was correlated with the substituent molar refraction (R _m ), hydrophobic constant () and Hammett constant ) of the guest compounds with a correlation coefficient of 0.95. The main driving forces for -cyclodextrin complexation was concluded to consist of van der Waals forces and hydrophobic interactions, while the influence of electronic effects was small.     

Phase Diagram of the Benzene–Dinitratotetrapyridinecopper(II) (Guest–Host) System and Thermodynamic Parameters for the Hostβ2Guest Clathrate Dissociation

In the first part of the work, thephase diagram of the benzene -ndash;[CuPy⁴(NO³)²] system has beendetermined in the -100 to +200 °C temperaturerange using DTA and solubility techniques. The onlycompound found in the system is the[CuPy⁴(NO³)²] 2C⁶H⁶clathrate. It is stable up to a temperature of+104.2(5) °C at which it melts incongruently togive liquid and the solid [CuPy⁴(NO³)²]host phase. At 146.1(5) °C exfoliation into twoliquid phases is observed, with the composition of themonotectic point being close to that of the clathrate.In the second part of the work, thermodynamicparameters of the clathrate dissociation have beendetermined from benzene vapour pressure strainmeasurements. For the process1/2 [CuPy⁴(NO³)²]2C⁶H⁶(solid) = 1/2 [CuPy⁴(NO³)²] (solid) +C⁶H⁶ (gas) H° = 45.3(3) kJ/mole; S₂₉₈° = 126(1) J/(mole K); G₂₉₈° = 7.7(5) kJ/mole.     

Physical and Chemical Properties of the Guest–Host Inclusion Complexes of Cyprofloxacin with β-Cyclodextrin Derivatives

Moscow University Chemistry Bulletin - We study the effect of the nature of the substituent in the β-cyclodextrin derivative on the physicochemical properties of the antibacterial drug...     

NMR Spectra of Guest–Host Complexes of Boron and Silicon Fluorides with Crown Ethers in Nonaqueous Solutions

¹⁹F, ¹¹B, and ²⁹Si NMR spectroscopy was used to examine the behavior of the guest–host complexes (BF₃· H₂O)₂· 18-crown-6 · 2H₂O, (BF₃· H₂O)₂· DCH-6B, and (DCH-6A · H₃O)SiF₅in acetone (DCH-6B and DCH-6A are the cis-anti-cis- and cis-syn-cis-isomers of dicyclohexano-18-crown-6, respectively). It was shown that molecular boron fluoride complexes undergo partial solvolysis in acetone to yield BF₃· acetone as the main product; the ionic pentafluorosilicate complex does not experience significant solvolysis transformations.     

A Microcalorimetric Study of Host–Guest Complexes of α-Cyclodextrin with Alkyl Trimethyl Ammonium Bromides in Aqueous Solutions

Interactions between α-CD and three alkyl trimethyl ammonium bromides, a homologues series of surfactants, in aqueous solutions have been investigated with titration microcalorimetry at 298.15 K. The results are discussed in the light of the amphiphilic interaction and the iceberg structure of water molecules existing around the hydrophobic tail of the surfactant. The stoichiometry of the host–guest complex changes from 1:1 to 2:1, as the number of carbon atoms (n) in the hydrophobic chain, C_nH_2n+1, increases from 8 to 14. All the complexes are quite stable, with the apparent experiential stability constants being β₁ = 2.65 × 10³ dm³-mol⁻¹, β₂ = 4.85 × 10⁶ dm⁶-mol⁻², β₂ = 6.50 × 10⁶ dm⁶-mol⁻², respectively for n = 8, 12, 14. All the complexation processes are shown to be enthalpy driven, and the standard enthalpy effect (−ΔH⁰) increases while standard entropy change (ΔS⁰) decreases with elongation of the hydrophobic chain.     

Host–Guest Complexation Using Pillar[5]arene Crystals: Crystal-Structure Dependent Uptake,Release, and Molecular Dynamics of an Alkane Guest

Host–guest complexation has been mainly investigated in solution, and it is unclear how guest molecules access the assembled structures of host and dynamics of guest molecules in the crystal state. In this study, we studied the uptake, release, and molecular dynamics of n-hexane vapor in the crystal state of pillar[5]arenes bearing different substituents. Pillar[5]arene bearing 10 ethyl groups yielded a crystal structure of herringbone-type 1:1 complexes with n-hexane, whereas pillar[5]arene with 10 allyl groups formed 1:1 complexes featuring a one-dimensional (1D) channel structure. For pillar[5]arene bearing 10 benzyl groups, one molecule of n-hexane was located in the cavity of pillar[5]arene, and another n-hexane molecule was located outside of the cavity between two pillar[5]arenes. The substituent-dependent differences in molecular arrangement influenced the uptake, release, and molecular dynamics of the n-hexane guest. The substituent effects were not observed in host–guest chemistry in solution, and these features are unique for the crystal state host–guest chemistry of pillar[5]arenes.     

Selective Arylation of β-Cyclodextrin with an Ethylenediamino Group and Characteristics of Arylated β-Cyclodextrin Derivatives in Host–Guest Complexation

Mono-3-deoxy-(N-benzoyl-ethylenediamino)--CD, mono-3-deoxy-(N-benzylidene-ethylenediamino)--CD and mono-3-deoxy-(N-salicylidene-ethylenediamino)--CD, each having a flexible chain that bonds the aryl moiety on the secondary side of -CD, were prepared. The reaction processes might involve the formation of mono-(2,3-manno-epoxide)--CD as an intermediate under our reaction conditions. Further experiments showed that the aryl moiety which was bonded as a functional group on the primary side of -CD or on the secondary side of -CD with or without an ethylenediamino chain show remarkably different complexation properties in the complexation with small molecular guests such as alkanes, cycloketones etc.     

Polarographic Studies on Anion Coordination Chemistry. Host–Guest Interactions of Hexacyclen and Pentacyclen with Pyrophosphate, Selenite, Selenate, Molybdate and Tungstate Anions

The complexation of protonated hexacyclen and pentacyclen with pyrophosphate, selenite, selenate, molybdate and tungstate anions was studied by differential pulse polarography at 25 °C. The stoichiometry and stability of the resulting anion complexes were evaluated from the pH and concentration-dependence of the peak potentials, respectively. The results established 1 : 1 anion receptor complexation in all cases. In the case of all anions studied, hexacyclen was found to form more stable anion complexes than pentacyclen. The fact that the anion-receptor complexation depends on the structural features of both the anions and the macrocycles used is indicative of a steric controlled interaction.     

Host–Guest Chemistry in the Gas Phase: Complex Formation of Cucurbit[6]uril with Proton-bound Water Dimer

The hydration of cucurbit[6]uril (CB[6]) in the gas phase is investigated using electrospray ionization traveling wave ion mobility mass spectrometry (ESI-TWIM-MS). Highly abundant dihydrated and tetrahydrated species of diprotonated CB[6] are found in the ESI-TWIM-MS spectrum. The hydration patterns of the CB[6] ion and the dissociation patterns of the hydrated CB[6] ion indicate that two water molecules are bound to each other, forming a water dimer in the CB[6] complex. Ion mobility studies combined with the structures calculated by density functional theory suggest that the proton-bound water dimer is present as a Zundel-like structure in the CB[6] portal, forming a hydrogen bond network with carbonyl groups of the CB[6]. When a large guest molecule is bound to a CB[6] portal, water molecules cannot bind to the portal. In addition, the strong binding energy of the water dimer blocks the portal, hindering the insertion of the long alkyl chain of the guest molecule into the CB[6] cavity. With small alkali metal cations, such as Li⁺ and Na⁺, a single water molecule interacts with the CB[6] portal, forming hydrogen bonds with the carbonyl groups of CB[6]. A highly stable Zundel-like structure of the proton-bound water dimer or a metal-bound water molecule at the CB[6] portal is suggested as an initial hydration process for CB[6], which is only dissolved in aqueous solution with acid or alkali metal ions.

Anion Binding Properties of Alkynylplatinum(II) Complexes with Amide-Functionalized Terpyridine: Host–Guest Interactions and Fluoride Ion-Induced Deprotonation

Molecular sensors able to detect ions are of interest due to their potential application in areas such as pollutant sequestration. Alkynylplatinum(II) terpyridine complexes with an amide-based receptor moiety have been synthesized and characterized. Their anion binding properties based on host–guest interactions have been examined with the use of UV-vis absorption and emission spectral titration studies. Spectral changes were observed for both complexes upon the addition of spherical and nonspherical anions. Their titration profiles were shown to be in good agreement with theoretical results predicting a 1:1 binding model, and the binding constants were determined from the experimental data. Drastic color changes from yellow to orange–red were observed for one of the complexes upon titration with fluoride (F⁻) ion in acetone. These changes were ascribed to the deprotonation of the amide functionalities induced by F⁻ ion, and this was confirmed by the restoration of spectral changes upon addition of trifluoroacetic acid to the F⁻ ion–complex mixture as well as by electrospray ionization mass spectrometry (ESI-MS) data.     

An Aggregation-Induced Emission-Based Fluorescence Turn-On Probe for Efficient Detection of HS− in Water,Wine, and Living Cells

Hydrogen sulfide (H₂S), as one of the important endogenous biological regulators, plays a critical role in mediating a wide range of physiological processes. The development of rapid, sensitive, and reliable detection techniques for H₂S would be highly appealing. In this paper, a new type of AIE-based fluorescence turn-on probe TPA-M for the detection of H₂S has been constructed, involved the rapid release of AIE-based fluorophore TPA-CHO with a remarkable fluorescence turn-on phenomenon in THF/H₂O (2/8, v/v, HEPES=20 μM, pH=7.3) medium, exhibiting the attractive advantages such as high sensitivity with the detection limit as low as 1.92×10⁻³ ppm, excellent selectivity over other anion analytes and biothiols, significant anti-interference ability and fast response time (within 10 min). What's more, the practical application evaluation indicated that the probe TPA-M could be efficiently employed in imaging exogenously added H₂S in living MCF-7 cells and detecting H₂S in actual water and wine samples.     

Supramolecular Photocatalysis by Utilizing the Host–Guest Charge-Transfer Interaction: Visible-Light-Induced Generation of Triplet Anthracenes for [4+2] Cycloaddition Reactions

Supramolecular photocatalysis via charge-transfer excitation of a host–guest complex was developed by use of the macrocyclic boronic ester [2+2]_BTH-F containing highly electron-deficient difluorobenzothiadiazole moieties. In the presence of a catalytic amount of [2+2]_BTH-F, the triplet excited state of anthracene was generated from the charge-transfer excited state of anthracene@[2+2]_BTH-F by visible-light irradiation, and cycloaddition of the excited anthracene with several dienes and alkenes proceeded in a [4+2] manner in high yields.     

Visualization of Host–Guest Interactions Between a Modified Nucleoside and Organic Moieties. Crystal Structures of 2'-Deoxy 5'-O-trityluridine and 2'-Deoxy 5'-O-tritylthymidine with Benzene, Toluene, Xylene, Trimethylbenzene, Cyclohexane and Water

This paper describes the crystal structures of 2'-deoxy 5'-O-trityluridine(5'-TU) and 2'-deoxy 5'-O-tritylthymidine (5'-TT) containing different organic moieties. There are two crystallographically independent nucleoside molecules present in the asymmetric units of all the structures. Uracil and thymine bases of the 2'-deoxy 5'-trityl uridine(5'-TU) and all the 2'-deoxy 5'-tritylthymidine structures are in an anti conformation with respect to their furanose rings. Thymine bases of molecules A and B form symmetric self pairs through N(3)-–O(2) hydrogen bonds, whereas uracil bases are not engaged in hydrogen bonding between themselves. Ribose moieties of both molecules of 2'-deoxy 5'-trityithymidine with benzene and toluene are in the C(2')-endo conformations while molecules A and B of 2'-deoxy 5'-tritylthymidine containing xylene, trimethylbenzene, cyclohexane and water are in the C(3')-endo and C(1')-exoconformations, respectively. Both ribose moieties of 5'-TU show C(3')-endo puckering. The conformation about the C(4')-–C(5') bond for all the 2'-deoxy 5'-tritylthymidine structures is g⁺, contrasting with the g^- for the 5'-TU structure. Benzene and toluene molecules stack between TT base pairs, while xylene, trimethylbenzene and cyclohexane are oriented obliquely to the base pairs. 2'-Deoxy 5'-tritylthymidine containing toluene shows a type V C-–H interaction between the methyl group of toluene and the thymine base. Remarkably, the 2'-deoxy 5'-tritylthymidine-containing xylene, trimethylbenzene, cyclohexane and water structures demonstrate a strong type I O-–H interaction between the ribose O(3') and the thymine base seen only in 1.25% of the structures. Molecular packing and hydrogen bonding are discussed.