Elucidating dissociation activation energies in host–guest assemblies featuring fast exchange dynamics

The ability to mediate the kinetic properties and dissociation activation energies (E_a) of bound guests by controlling the characteristics of “supramolecular lids” in host–guest molecular systems is essential for both their design and performance. While the synthesis of such systems is well advanced, the experimental quantification of their kinetic parameters, particularly in systems experiencing fast association and dissociation dynamics, has been very difficult or impossible with the established methods at hand. Here, we demonstrate the utility of the NMR-based guest exchange saturation transfer (GEST) approach for quantifying the dissociation exchange rates (k_out) and activation energy (E_a,out) in host–guest systems featuring fast dissociation dynamics. Our assessment of the effect of different monovalent cations on the extracted E_a,out in cucurbit[7]uril:guest systems with very fast k_out highlights their role as “supramolecular lids” in mediating a guest''s dissociation E_a. We envision that GEST could be further extended to study kinetic parameters in other supramolecular systems characterized by fast kinetic properties and to design novel switchable host–guest assemblies.

GEST-NMR is utilized for quantifying the dissociation activation energy (E_a,out) in host-guest systems featuring fast dissociation dynamics.     

Catalytic electron drives host–guest recognition

Electron injection is demonstrated to trigger electrocatalytic chain reactions capable of releasing a solvent molecule and forming a redox active guest molecule. One-electron reduction of a hydroxy anthrone derivative (AQH–CH₂CN) results in the formation of an anthraquinone radical anion (AQ˙⁻) and acetonitrile (CH₃CN). The resulting fragment of AQ˙⁻ exhibits high stability under mild reducing conditions, and it has enough reducing power to reduce the reactant of AQH–CH₂CN. Hence, subsequent electron transfer from AQ˙⁻ to AQH–CH₂CN yields the secondary AQ˙⁻ and CH₃CN, while the initial AQ˙⁻ is subsequently oxidized to AQ. Overall, the reactants of AQH–CH₂CN are completely converted into AQ and CH₃CN in sustainable electrocatalytic chain reactions. These electrocatalytic chain reactions are mild and sustainable, successfully achieving catalytic electron-triggered charge-transfer (CT) complex formation. Reactant AQH–CH₂CN is non-planar, making it unsuitable for CT interaction with an electron donor host compound (U_HAnt₂) bearing parallel anthracene tweezers. However, conversion of AQH–CH₂CN to planar electron acceptor AQ by the electrocatalytic chain reactions turns on CT interaction, generating a host CT complex with U_HAnt₂ (AQ ⊂ U_HAnt₂). Therefore, sustainable electrocatalytic chain reactions can control CT interactions using only a catalytic amount of electrons, ultimately affording a one-electron switch associated with catalytic electron-triggered turn-on molecular recognition.

The reactants of AQH–CH₂CN are converted into AQ and CH₃CN in sustainable electrocatalytic chain reactions, successfully achieving catalytic electron-triggered charge-transfer (CT) complex formation.     

Boosting purely organic room-temperature phosphorescence performance through a host–guest strategy

The host–guest doping system has aroused great attention due to its promising advantage in stimulating bright and persistent room-temperature phosphorescence (RTP). Currently, exploration of the explicit structure–property relationship of bicomponent systems has encountered obstacles. In this work, two sets of heterocyclic isomers showing promising RTP emissions in the solid state were designed and synthesized. By encapsulating these phosphors into a robust phosphorus-containing host, several host–guest cocrystalline systems were further developed, achieving highly efficient RTP performance with a phosphorescence quantum efficiency (ϕ_P) of ∼26% and lifetime (τ_P) of ∼32 ms. Detailed photophysical characterization and molecular dynamics (MD) simulation were conducted to reveal the structure–property relationships in such bicomponent systems. It was verified that other than restricting the molecular configuration, the host matrix could also dilute the guest to avoid concentration quenching and provide an external heavy atom effect for the population of triplet excitons, thus boosting the RTP performance of the guest.

Several host–guest cocrystal systems with bright and persistent room-temperature phosphorescence were developed by utilizing a phosphorus-containing material as a robust host and newly developed isomeric organic phosphors as guests.     

Exploiting host–guest chemistry to manipulate magnetic interactions in metallosupramolecular M4L6 tetrahedral cages

Reaction of Ni(OTf)₂ with the bisbidentate quaterpyridine ligand L results in the self-assembly of a tetrahedral, paramagnetic cage [Ni^II₄L₆]⁸⁺. By selectively exchanging the bound triflate from [OTf⊂Ni^II₄L₆](OTf)₇ (1), we have been able to prepare a series of host–guest complexes that feature an encapsulated paramagnetic tetrahalometallate ion inside this paramagnetic host giving [M^IIX₄⊂Ni^II₄L₆](OTf)₆, where M^IIX₄²⁻ = MnCl₄²⁻ (2), CoCl₄²⁻ (5), CoBr₄²⁻ (6), NiCl₄²⁻ (7), and CuBr₄²⁻ (8) or [M^IIIX₄⊂Ni^II₄L₆](OTf)₇, where M^IIIX₄⁻ = FeCl₄⁻ (3) and FeBr₄⁻ (4). Triflate-to-tetrahalometallate exchange occurs in solution and can also be accomplished through single-crystal-to-single-crystal transformations. Host–guest complexes 1–8 all crystallise as homochiral racemates in monoclinic space groups, wherein the four {NiN₆} vertexes within a single Ni₄L₆ unit possess the same Δ or Λ stereochemistry. Magnetic susceptibility and magnetisation data show that the magnetic exchange between metal ions in the host [Ni^II₄] complex, and between the host and the MX₄ⁿ⁻ guest, are of comparable magnitude and antiferromagnetic in nature. Theoretically derived values for the magnetic exchange are in close agreement with experiment, revealing that large spin densities on the electronegative X-atoms of particular MX₄ⁿ⁻ guest molecules lead to stronger host–guest magnetic exchange interactions.

The tetrahedral [Ni^II₄L₆]⁸⁺ cage can reversibly bind paramagnetic MX₄^1/2− guests, inducing magnetic exchange interactions between host and guest.     

Modular synthesis,host–guest complexation and solvation-controlled relaxation of nanohoops with donor–acceptor structures

Carbon nanohoops with donor–acceptor (D–A) structures are attractive electronic materials and biological fluorophores, but their synthesis is usually challenging. Moreover, the preparation of D–A nanohoop fluorophores exhibiting high fluorescence quantum yields beyond 500 nm remains a key challenge. This study presents a modular synthetic approach based on an efficient metal-free cyclocondensation reaction that readily produced nine congeners with D–A or donor–acceptor–donor′ (D–A–D′) structures, one of which is water-soluble. The tailored molecular design of nanohoops enabled a systematic and detailed study of their host–guest complexation with fullerene, optical properties, and charge transfer (CT) dynamics using X-ray crystallography, fluorescence titration, steady and ultrafast transient absorption spectroscopy, and theoretical calculations. The findings revealed intriguing physical properties associated with D–A motifs, such as tight binding with fullerene, moderate fluorescence quantum yields (37–67%) beyond 540 nm, and unique solvation-controlled CT relaxation of D–A–D′ nanohoops, where two CT states (D–A and A–D′) can be effectively tuned by solvation, resulting in dramatically changed relaxation pathways in different solvents.

A modular synthetic approach based on cyclocondensation reaction is introduced to produce nine nanohoops with tunable donor–acceptor structures.     

Fluorescence detected circular dichroism (FDCD) for supramolecular host–guest complexes

Fluorescence-detected circular dichroism (FDCD) spectroscopy is applied for the first time to supramolecular host–guest and host–protein systems and compared to the more known electronic circular dichroism (ECD). We find that FDCD can be an excellent choice for common supramolecular applications, e.g. for the detection and chirality sensing of chiral organic analytes, as well as for reaction monitoring. Our comprehensive investigations demonstrate that FDCD can be conducted in favorable circumstances at much lower concentrations than ECD measurements, even in chromophoric and auto-emissive biofluids such as blood serum, overcoming the sensitivity limitation of absorbance-based chiroptical spectroscopy. Besides, the combined use of FDCD and ECD can provide additional valuable information about the system, e.g. the chemical identity of an analyte or hidden aggregation phenomena. We believe that simultaneous FDCD- and ECD-based chiroptical characterization of emissive supramolecular systems will be of general benefit for characterizing fluorescent, chiral supramolecular systems due to the higher information content obtained by their combined use.

Fluorescence-detected circular dichroism (FDCD) spectroscopy is applied for the first time to supramolecular host–guest and host–protein systems and compared to the more known electronic circular dichroism (ECD).     

Multiplexed optical barcoding of cells via photochemical programming of bioorthogonal host–guest recognition

Modern chemical and biological studies are undergoing a paradigm shift, where understanding the fate of individual cells, in an apparently homogeneous population, is becoming increasingly important. This has inculcated a growing demand for developing strategies that label individual cells with unique fluorescent signatures or barcodes so that their spatiotemporal trajectories can be mapped in real time. Among various approaches, light-regulated methods employing photocaged fluorophores have received particular attention, owing to their fine spatiotemporal control over labelling. However, their multiplexed use to barcode large numbers of cells for interrogating cellular libraries or complex tissues remains inherently challenging, due to the lack of multiple spectrally distinct photoactivated states in the currently available photocaged fluorophores. We report here an alternative multiplexable strategy based on optically controlled host–guest recognition in the cucurbit[7]uril (CB[7]) system that provides spatial control over the positioning of fluorophores to generate distinct barcodes in ‘user-defined’ cells. Using a combination of three spectrally distinct CB[7]-conjugated fluorophores and by sequentially performing cycles of photoactivation and fluorophore encoding, we demonstrate 10-color barcoding in microtubule-targeted fixed cells as well as 7-color barcoding in cell surface glycan targeted live MCF7 cells.

Barcoding provides abilities to learn about individual species within an apparently homogeneous population. We describe a light-mediated multiplexed cellular barcoding strategy through spatial programming of cucurbit[7]uril molecular recognition.     

A host–guest strategy for converting the photodynamic agents from a singlet oxygen generator to a superoxide radical generator

Type-I photosensitizers (PSs) generate cytotoxic oxygen radicals by electron transfer even in a hypoxic environment. Nevertheless, the preparation of type-I PSs remains a challenge due to the competition of triplet–triplet energy transfer with O₂ (type-II process). In this work, we report an effective strategy for converting the conventional type-II PS to a type-I PS by host–guest complexation. Electron-rich pillar[5]arenes are used as an electron donor and macrocyclic host to produce a host–guest complex with the traditional electron-deficient type-II PS, an iodide BODIPY-based guest. The host–guest complexation promotes intermolecular electron transfer from the pillar[5]arene moiety to BODIPY and then to O₂ by the type-I process upon light-irradiation, leading to efficient generation of the superoxide radical (O₂⁻˙). The results of anti-tumor studies indicate that this supramolecular PS demonstrates high photodynamic therapy efficacy even under hypoxic conditions. This work provides an efficient method to prepare type-I PSs from existing type-II PSs by using a supramolecular strategy.

A supramolecular strategy is reported for converting the conventional photodynamic agents from a singlet oxygen generator to a superoxide radical generator by the host–guest interaction enhanced electron transfer.     

Efficient and organic host–guest room-temperature phosphorescence: tunable triplet–singlet crossing and theoretical calculations for molecular packing

Organic host–guest doped materials exhibiting the room temperature phosphorescence (RTP) phenomenon have attracted considerable attention. However, it is still challenging to investigate their corresponding luminescence mechanism, because for host–guest systems, it is very difficult to obtain single crystals compared to single-component or co-crystal component materials. Herein, we developed a series of organic doped materials with triphenylamine (TPA) as the host and TPA derivatives with different electron-donating groups as guests. The doped materials showed strong fluorescence, thermally activated delayed fluorescence (τ: 39–47 ms), and efficient room temperature phosphorescence (Φ_phos: 7.3–9.1%; τ: 170–262 ms). The intensity ratio between the delayed fluorescence and phosphorescence was tuned by the guest species and concentration. Molecular dynamics simulations were used to simulate the molecular conformation of guest molecules in the host matrix and the interaction between the host and guest molecules. Therefore, the photophysical properties were calculated using the QM/MM model. This work provides a new concept for the study of molecular packing of guest molecules in the host matrix.

Molecular dynamics simulations were used to simulate the molecular conformation and interaction between hosts and guests. This work provides a new concept for the study of molecular packing for the investigation of the luminescence mechanism.     

Controlling the alignment of 1D nanochannel arrays in oriented metal–organic framework films for host–guest materials design

Controlling the direction of molecular-scale pores enables the accommodation of guest molecular-scale species with alignment in the desired direction, allowing for the development of high-performance mechanical, thermal, electronic, photonic and biomedical organic devices (host–guest approach). Regularly ordered 1D nanochannels of metal–organic frameworks (MOFs) have been demonstrated as superior hosts for aligning functional molecules and polymers. However, controlling the orientation of MOF films with 1D nanochannels at commercially relevant scales remains a significant challenge. Here, we report the fabrication of macroscopically oriented films of Cu-based pillar-layered MOFs having regularly ordered 1D nanochannels. The direction of 1D nanochannels is controllable by optimizing the crystal growth process; 1D nanochannels align either perpendicular or parallel to substrates, offering molecular-scale pore arrays for a macroscopic alignment of functional guest molecules in the desired direction. Due to the fundamental interest and widespread technological importance of controlling the alignment of functional molecules and polymers in a particular direction, orientation-controllable MOF films will open up the possibility of realising the potential of MOFs in advanced technologies.

Orientation-controlled Cu₂(Linker)₂DABCO MOF films on macroscopic scales are fabricated for the development of high-performance devices; the direction of 1D nanochannels is controllable either perpendicular or parallel to substrates.     

A pillar[5]arene-based covalent organic framework with pre-encoded selective host–guest recognition

It is highly desirable to maintain both permanent accessible pores and selective molecular recognition capability of macrocyclic cavitands in the solid state. Integration of well-defined discrete macrocyclic hosts into ordered porous polymeric frameworks (e.g., covalent organic frameworks, COFs) represents a promising strategy to transform many supramolecular chemistry concepts and principles well established in the solution phase into the solid state, which can enable a broad range of practical applications, such as high-efficiency molecular separation, heterogeneous catalysis, and pollution remediation. However, it is still a challenging task to construct macrocycle-embedded COFs. In this work, a novel pillar[5]arene-derived (P5) hetero-porous COF, denoted as P5-COF, was rationally designed and synthesized. Featuring the unique backbone structure, P5-COF exhibited selective adsorption of C₂H₂ over C₂H₄ and C₂H₆, as well as significantly enhanced host–guest binding interaction with paraquat, in comparison with the pillar[5]arene-free COF analog, Model-COF. The present work established a new strategy for developing COFs with customizable molecular recognition/separation properties through the bottom-up “pre-porous macrocycle to porous framework” design.

A novel pillar[5]arene-derived (P5) COF was rationally designed and synthesized, which exhibited superior performance in selective gas adsorption and paraquat binding.     

Polymorphism of a widely used building block for halogen‐bonded assemblies: 1,3,5‐trifluoro‐2,4,6‐triiodobenzene

After reporting the structure of a new polymorph of 1,3,5‐trifluoro‐2,4,6‐triiodobenzene (denoted BzF3I3 ), C₆F₃I₃, (I), which crystallized in the space group P 2₁/c , we perform a comparative analysis with the already reported P 2₁/n polymorph, (II) [Reddy et al. (2006). Chem. Eur. J. 12 , 2222–2234]. In polymorph (II), type‐II I…I halogen bonds and I…π interactions connect molecules in such a way that a three‐dimensional structure is formed; however, the way in which molecules are connected in polymorph (I), through type‐II I…I halogen bonds and π–π interactions, gives rise to an exfoldable lamellar structure, which looks less tightly bound than that of (II). In agreement with this structural observation, both the melting point and the melting enthalpy of (I) are lower than those of (II).     

Ferrocenylpyrazole—A versatile building block for hydrogen-bonded organometallic supramolecular assemblies

The crystal architectures of 5-ferrocenylpyrazole (1) and its metal complexes were investigated. Compound 1 can form non-solvated and chloroform-solvated crystals. In both cases, 1 forms a zigzag one-dimensional architecture via NH?N hydrogen bonds. The hydrogen bond exhibits a twofold disorder, which was shown to be static by solid-state ¹³C NMR. In the solvated crystal, the chloroform is released at 415 K, associated with melting of the crystal. The reaction of 1 with metal salts provided metal-centered ferrocenyl clusters [Zn(NO₃)₂(1)₄] (4), [Co(NO₃)₂(1)₄] (5), [CoCl₂(1)₄] (6), [Zn(NCS)₂(1)₂] (7), cis-[Pt(NH₃)₂(1)₂](PF₆)₂ (8), and trans-[Pt(NH₃)₂(1)₄](PF₆)₂ (9). In all of these complexes, 1 acts as a monodentate ligand. In 4, 5, and 7, the multinuclear units are joined via hydrogen bonds to form supramolecular chains. Two polymorphs were found for the crystals of 4. Both are composed of the same hydrogen-bonded chains, but their arrangements are different. 5-Ferrocenyl-1-tritylpyrazole (2) and 4-ferrocenyl-1-methylpyrazole (3) were also crystallographically characterized.     

Water as a building block in solid-state acetonitrile-pyrogallol[4]arene assemblies: structural investigations

Under various conditions, water molecules dramatically affect a number of solid-state C-alkylpyrogallol[4]arene assemblies. In the absence of water, hydrogen-bonded hexameric capsules are formed for the C-butyl, pentyl, hexyl, and heptyl pyrogallol[4]arenes. Introduction of water to acetonitrile solutions containing C-propyl-C-octylpyrogallol[4]arenes resulted in the formation of markedly different bilayer structures and the structural identification of two new dimer-type motifs.     

Optosensing of cationic surfactants based on host–guest chemistry

An optode membrane for cationic surfactants is presented. Plasticized poly(vinyl chloride) (PVC) membranes incorporating the hexaester of calix[6]arene and the neutral H⁺-selective chromo-ionophore (ETH5294) have proved to be excellent reversible sensing devices for cationic surfactants as exemplified by cetyltrimethylammonium bromide (CTMAB). Based on host–guest chemistry, the guest molecule CTMAB was extracted into the PVC membrane, forming a host–guest adduct with the host molecule calix[6]arene ionophore and causing a concomitant release of a proton from the protonated ETH5294 into the solution. Upon deprotonation, ETH5294 undergoes a color change which can be used as a means for the quantitation of CTMAB. Unlike small inorganic cations, such as K⁺ and Na⁺, the experimental results show that the membrane response depends to a great extent on the migration process of CTMAB from the bulk of the solution to the membrane interface. A modified theoretical equation describing the membrane response on the CTMAB concentrations has been derived and shown to be in conformity with the experimental results.     

Linear viscoelastic studies on a transient network formed by host–guest interaction

A host–guest (HG) polymer was prepared through the radical polymerization of acrylamide monomers (AAm) with a small amount of host‐guest linkers, β‐cyclodextrin‐attached AAm (βCD‐AAm) and adamantane‐attached AAm (Ad‐AAm). The linear viscoelastic and swelling measurements indicated that the resulting HG polymer swollen in water was gel‐like, although the HG polymer is conceptually a linear chain having only temporary crosslinkings. NMR measurements indicated that half of the βCD units incorporated in the HG polymer do not form the inclusion complex with Ad. Rheological analysis of the HG polymer revealed that HG interaction retarded the Rouse modes of networks but did not affect the level of the plateau modulus, which was simply described by the entanglements of AAm chains. This result was confirmed with the reference experiment, in which Ad were capped by competitive βCD molecules. Furthermore, the PAAm polymer with only βCD units (no Ad) was found to exhibit gel‐like behavior. This behavior was attributed to the formation of a small amount of rotaxane structure, which act as permanent crosslinkings, based on 2D NMR data. The HG polymer is basically an entanglement network with temporary sticky points due to the HG interaction, and a few permanent branching points. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 1109–1117     

Reconstructing reactivity in dynamic host–guest systems at atomistic resolution: amide hydrolysis under confinement in the cavity of a coordination cage

Spatial confinement is widely employed by nature to attain unique efficiency in controlling chemical reactions. Notable examples are enzymes, which selectively bind reactants and exquisitely regulate their conversion into products. In an attempt to mimic natural catalytic systems, supramolecular metal–organic cages capable of encapsulating guests in their cavity and of controlling/accelerating chemical reactions under confinement are attracting increasing interest. However, the complex nature of these systems, where reactants/products continuously exchange in-and-out of the host, makes it often difficult to elucidate the factors controlling the reactivity in dynamic regimes. As a case study, here we focus on a coordination cage that can encapsulate amide guests and enhance their hydrolysis by favoring their mechanical twisting towards reactive molecular configurations under confinement. We designed an advanced multiscale simulation approach that allows us to reconstruct the reactivity in such host–guest systems in dynamic regimes. In this way, we can characterize amide encapsulation/expulsion in/out of the cage cavity (thermodynamics and kinetics), coupling such host–guest dynamic equilibrium with characteristic hydrolysis reaction constants. All computed kinetic/thermodynamic data are then combined, obtaining a statistical estimation of reaction acceleration in the host–guest system that is found in optimal agreement with the available experimental trends. This shows how, to understand the key factors controlling accelerations/variations in the reaction under confinement, it is necessary to take into account all dynamic processes that occur as intimately entangled in such host–guest systems. This also provides us with a flexible computational framework, useful to build structure–dynamics–property relationships for a variety of reactive host–guest systems.

Encapsulation of guests in metal–organic cages allows control over chemical reactivity. Focusing on the hydrolysis of amides, here we show an effective molecular simulation approach to reconstruct reactivity in host–guest systems in dynamic regimes.     

Theoretical analyses of the host–guest interaction within chlorine hydrate

The host–guest interaction is necessary for the stabilization of hydrates. Using Density Function Theory methods, the host–guest interaction within an unconventional chlorine hydrate was investigated, in combination with typical noncovalent analyses. The host–guest interaction energy was predicted to be as high as 17.51 kcal/mol, which was stronger than the typical van der Waals (vdW) interaction, due to an involvement of up to 20 Cl…O interactions. Polarization and dispersion energies made up the main contribution to the total interaction energy. Further visualization of the host–guest interaction validated, together with the general Cl…O interaction, another vdW interaction between the guest‐Cl atom and the five‐membered H₂O cluster. Isosurfaces associated with two patterns of vdW interactions yielded a better “fit” in shape, suggesting their cooperativity in stabilizing the steric configuration. The σ‐region on the guest‐Cl atom was verified to regulate the electron redistribution over the molecular space. These results are useful for understanding specific halogen behavior, and the origin and nature of host–guest interaction in hydrates. © 2013 Wiley Periodicals, Inc.     

Positioning lithium ions by host–guest chemistry combined with self‐assembly using a thiophene‐based all‐conjugated amphiphilic block copolymer

Self‐assembly of poly(3‐hexylthiophene) ( P3HT) driven by π–π stacking, combined with “Host‐Guest Chemistry” of ethylene glycol oligomer and lithium ion is demonstrated using a thiophene‐based all conjugated amphiphilic block copolymer, containing 93 mol % of P3HT and 7 mol % of poly(3‐(2‐(2‐{2‐[2‐(2‐methoxy‐ethoxy)‐ethoxy]‐ethoxy}‐ethyl))thiophene), P3EGT blocks. An ion chelating ability of ethylene glycol oligomers with lithium ions in the P3EGT block is confirmed using ¹H‐NMR spectrometry. This method could allow positioning lithium ions at the interface between P3HT domains and PC₆₁BM clusters, confirmed using XRD and photoluminescence quenching experiments. The compact lamellar P3HT domains by side repulsion driven self‐assembly of amphiphilic block copolymer and the molecular engineering of the interface with an optimized lithium contents are resulted in the improvement of photovoltaic performance in an organic solar cell (2.1–3.0%). © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1068–1074