Guest Binding Research Articles

Comprehensive evaluation of end-point free energy techniques in carboxylated-pillar[6]arene host-guest binding: I. Standard procedure.

Despite the massive application of end-point free energy methods in protein-ligand and protein-protein interactions, computational understandings about their performance in relatively simple and prototypical host-guest systems are limited. In this work, we present a comprehensive benchmark calculation with standard end-point free energy techniques in a recent host-guest dataset containing 13 host-guest pairs involving the carboxylated-pillar[6]arene host. We first assess the charge schemes for solutes by comparing the charge-produced electrostatics with many ab initio references, in order to obtain a preliminary albeit detailed view of the charge quality. Then, we focus on four modelling details of end-point free energy calculations, including the docking procedure for the generation of initial condition, the charge scheme for host and guest molecules, the water model used in explicit-solvent sampling, and the end-point methods for free energy estimation. The binding thermodynamics obtained with different modelling schemes are compared with experimental references, and some practical guidelines on maximizing the performance of end-point methods in practical host-guest systems are summarized. Further, we compare our simulation outcome with predictions in the grand challenge and discuss further developments to improve the prediction quality of end-point free energy methods. Overall, unlike the widely acknowledged applicability in protein-ligand binding, the standard end-point calculations cannot produce useful outcomes in host-guest binding and thus are not recommended unless alterations are performed.

An Organo‐Palladium Host Built from a Dynamic Macrocyclic Ligand: Adaptive Self‐Assembly, Induced‐Fit Guest Binding, and Catalysis

AbstractArtificial hosts with rich conformational dynamics are attractive to supramolecular chemists due to their adaptive guest‐binding properties and enzyme‐like catalytic functions. We report here the adaptive self‐assembly and host‐guest catalysis of a new water‐soluble organo‐palladium host (Pd2L2) built from a pyridinium‐bonded macrocyclic ligand (L) andcis‐blocked palladium corners (Pd). While the direct self‐assembly of L with Pd gives rise to a dynamic mixture of products, both neutral polyaromatic hydrocarbons and an anionic polyoxometalate cluster (W10O324−) can template the dominant formation of the Pd2L2host. Guest‐adaptive conformational changes and induced‐fit cavity deformation of the Pd2L2host have been clearly observed in the crystal structures. Moreover, the installation of the electron‐rich W10O324−cluster within the cationic redox‐active host (W10O32⊂Pd2L2) facilitates the efficient and selective C−H photooxidation of toluene derivatives to aldehyde products under mild conditions, thus representing an ideal platform for green supramolecular catalysis.

An Organo-Palladium Host Built from a Dynamic Macrocyclic Ligand: Adaptive Self-Assembly, Induced-Fit Guest Binding, and Catalysis.

Artificial hosts with rich conformational dynamics are attractive to supramolecular chemists due to their adaptive guest-binding properties and enzyme-like catalytic functions. We report here the adaptive self-assembly and host-guest catalysis of a new water-soluble organo-palladium host (Pd2 L2 ) built from a pyridinium-bonded macrocyclic ligand (L) and cis-blocked palladium corners (Pd). While the direct self-assembly of L with Pd gives rise to a dynamic mixture of products, both neutral polyaromatic hydrocarbons and an anionic polyoxometalate cluster (W10 O32 4- ) can template the dominant formation of the Pd2 L2 host. Guest-adaptive conformational changes and induced-fit cavity deformation of the Pd2 L2 host have been clearly observed in the crystal structures. Moreover, the installation of the electron-rich W10 O32 4- cluster within the cationic redox-active host (W10 O32 ⊂Pd2 L2 ) facilitates the efficient and selective C-H photooxidation of toluene derivatives to aldehyde products under mild conditions, thus representing an ideal platform for green supramolecular catalysis.

Construction of Photo-Responsive Pd2 L4 -Type Nanocages based on Feringa's Second-Generation Motor and Its Guest Binding Ability for C60.

We present the construction of a M2 L4 -type metal-organic nanocage featuring four endohedral Feringa's motor motifs and its adaptive encapsulation towards a C60 guest molecule. The structure of the cage, though complicated on the 1 H NMR spectrum due to the adoption of mixed ligands, was unambiguously characterized with a combination of ESI-MS, 2D DOSY, 13 C NMR and particularly the SAXS technique. The molecular motor within the cage demonstrated similar photophysical properties to the uncoordinated one, indicating the motor's function was not compromised when it was anchored in such a confined nanospace. Furthermore, the nanocage showed good guest encapsulation ability towards C60 , and a guest induced-fit behavior of the cage was revealed based on the extensive SAXS analysis and molecular dynamics simulation. The adaptive motorized nanocage reported here represents one of the very few examples of integrating individual motors into a discrete nanoconfined system and offers prospects to achieve its non-equilibrium functions.

Adaptive Binding of Alkyl Glycosides by Nonpeptidic Helix Bundles in Water: Toward Artificial Glycolipid Binding Proteins.

Amphipathic water-soluble helices formed from synthetic peptides or foldamers are promising building blocks for the creation of self-assembled architectures with non-natural shapes and functions. While rationally designed artificial quaternary structures such as helix bundles have been shown to contain preformed cavities suitable for guest binding, there are no examples of adaptive binding of guest molecules by such assemblies in aqueous conditions. We have previously reported a foldamer 6-helix bundle that contains an internal nonpolar cavity able to bind primary alcohols as guest molecules. Here, we show that this 6-helix bundle can also interact with larger, more complex guests such as n-alkyl glycosides. X-ray diffraction analysis of co-crystals using a diverse set of guests together with solution and gas-phase studies reveals an adaptive binding mode whereby the apo form of the 6-helix bundle undergoes substantial conformational change to accommodate the hydrocarbon chain in a manner reminiscent of glycolipid transfer proteins in which the cavity forms upon lipid uptake. The dynamic nature of the self-assembling and molecular recognition processes reported here marks a step forward in the design of functional proteomimetic molecular assemblies.

Leveraging quantum-chemical in silico techniques to determine guest binding energies for the crystalline sponge method

Leveraging quantum-chemical <i>in silico</i> techniques to determine guest binding energies for the crystalline sponge method

Metal Organic Framework for SO2 Capture

Metal-organic framework (MOF) is a poriferous 3D framework, composed of organic ligands and central metal ions. The MOFs are often preferred for SO2 capture due to their ligand function, large pore volume, simplicity of preparation as well as their relatively low cost of reactivation. In this review, the synthesis strategies achieving the formation of MOFs with higher porosity and strengthened reversibility were introduced. The synthesis processes include conventional heating, modulated synthesis, and post-synthetic modification (PSM). Conventional heating is categorized into two different methods, including electric heating and solvothermal synthesis. Electric heating usually involves using temperature change to produce target MOF whereas solvothermal synthesis is defined as reactions in enclosed containers under autogenic pressure past the boiling point of the solvent. Modulated synthesis and PSM also guarantee low by-products and great stability. The mechanisms of SO2 adsorption were also discussed, which mainly focused on the physisorption that enables the utilizing resources to be efficiently used, as MOFs with physisorption are reusable. The adsorption site including strong hydrogen bonds and the uncoordinated atom with strong electronegativity also determines MOF’s ability. In addition, the influencing factors were interpreted to help demonstrate the mechanism of SO2 adsorption. The SO2 adsorption in the MOF is influenced by the pore structure, both the pore arrangement and the pore size, the guest binding to the SO2 and the linkers to the SO2.

Structural and Dynamic Analysis of Sulphur Dioxide Adsorption in a Series of Zirconium-Based Metal-Organic Frameworks.

We report reversible high capacity adsorption of SO2 in robust Zr‐based metal–organic framework (MOF) materials. Zr‐bptc (H4bptc=biphenyl‐3,3′,5,5′‐tetracarboxylic acid) shows a high SO2 uptake of 6.2 mmol g−1 at 0.1 bar and 298 K, reflecting excellent capture capability and removal of SO2 at low concentration (2500 ppm). Dynamic breakthrough experiments confirm that the introduction of amine, atomically‐dispersed CuII or heteroatomic sulphur sites into the pores enhance the capture of SO2 at low concentrations. The captured SO2 can be converted quantitatively to a pharmaceutical intermediate, aryl N‐aminosulfonamide, thus converting waste to chemical values. In situ X‐ray diffraction, infrared micro‐spectroscopy and inelastic neutron scattering enable the visualisation of the binding domains of adsorbed SO2 molecules and host–guest binding dynamics in these materials at the atomic level. Refinement of the pore environment plays a critical role in designing efficient sorbent materials.

Structural and Dynamic Analysis of Sulphur Dioxide Adsorption in a Series of Zirconium‐Based Metal–Organic Frameworks

We report reversible high capacity adsorption of SO2 in robust Zr-based metal–organic framework (MOF) materials. Zr-bptc (H4bptc=biphenyl-3,3′,5,5′-tetracarboxylic acid) shows a high SO2 uptake of 6.2 mmol g−1 at 0.1 bar and 298 K, reflecting excellent capture capability and removal of SO2 at low concentration (2500 ppm). Dynamic breakthrough experiments confirm that the introduction of amine, atomically-dispersed CuII or heteroatomic sulphur sites into the pores enhance the capture of SO2 at low concentrations. The captured SO2 can be converted quantitatively to a pharmaceutical intermediate, aryl N-aminosulfonamide, thus converting waste to chemical values. In situ X-ray diffraction, infrared micro-spectroscopy and inelastic neutron scattering enable the visualisation of the binding domains of adsorbed SO2 molecules and host–guest binding dynamics in these materials at the atomic level. Refinement of the pore environment plays a critical role in designing efficient sorbent materials.

Recent advances in macrocyclic arenes-based fluorescent indicator displacement assays.

Macrocyclic arenes-based fluorescent indicator displacement assays (F-IDAs) offer a unique and innovative approach to chemosensing, taking molecular recognition in host-guest chemistry to a higher level. Because of their special architecture and versatile host–guest binding properties, macrocyclic arenes, principally calix[n]arenes and, in recent years, pillar[n]arenes, in combination with various fluorophores, are widely used in F-IDAs for the specific and selective sensing of cationic, anionic, and neutral analytes. In this paper, we review recent progress in the development of F-IDAs based on macrocyclic arenes and outline the prospects and remaining challenges relating to macrocyclic arenes-based F-IDAs.

Self‐Regulated Pathway‐Dependent Chirality Control of Silver Nanoclusters

AbstractImparting chirality affords additive values, functions and responsiveness in molecular systems including nanoscale materials. Here, we report pathway‐dependent chirality control in silver nanoclusters (NCs). The use of enantiomeric ligand, α‐dihydrolipoic acid (DHLA), for the synthesis of Ag NCs leads to the preferential formation of one‐handed chiral Ag29(DHLA)12 NCs with intrinsic chirality in the exterior shell composed of a silver‐dithiolate framework. Small Lewis base molecules such as pyridine bind to silver atoms in the shell of NC as a guest. The guest binding reverses the relative stability between the right‐ and left‐handed NCs upon a steric interaction with the chiral ligand DHLA in the exterior shell in a kinetic manner, leading to unprecedented chirality inversion in the synthesis of NCs. This mechanism is further extended to the self‐regulation or self‐replication of chirality through interNC interactions dependent on the concentration in the synthesis of NCs.

Self-Regulated Pathway-Dependent Chirality Control of Silver Nanoclusters.

Imparting chirality affords additive values, functions and responsiveness in molecular systems including nanoscale materials. Here, we report pathway-dependent chirality control in silver nanoclusters (NCs). The use of enantiomeric ligand, α-dihydrolipoic acid (DHLA), for the synthesis of Ag NCs leads to the preferential formation of one-handed chiral Ag29 (DHLA)12 NCs with intrinsic chirality in the exterior shell composed of a silver-dithiolate framework. Small Lewis base molecules such as pyridine bind to silver atoms in the shell of NC as a guest. The guest binding reverses the relative stability between the right- and left-handed NCs upon a steric interaction with the chiral ligand DHLA in the exterior shell in a kinetic manner, leading to unprecedented chirality inversion in the synthesis of NCs. This mechanism is further extended to the self-regulation or self-replication of chirality through interNC interactions dependent on the concentration in the synthesis of NCs.

Host–guest binding selectivity of ethylated pillar[5]arene (EtP5A) towards octane, 1,7-octadiene, and 1,7-octadiyne: a computational investigation

Host–guest binding selectivity of ethylated pillar[5]arene (EtP5A) towards octane, 1,7-octadiene, and 1,7-octadiyne: a computational investigation

Guest-Modulated Circularly Polarized Luminescence by Ligand-to-Ligand Chirality Transfer in Heteroleptic PdII Coordination Cages.

Multicomponent metallo‐supramolecular assembly allows the rational combination of different building blocks. Discrete multifunctional hosts with an accessible cavity can be prepared in a non‐statistical fashion. We employ our shape‐complementary assembly (SCA) method to achieve for the first time integrative self‐sorting of heteroleptic PdII cages showing guest‐tunable circularly polarized luminescence (CPL). An enantiopure helicene‐based ligand (M or P configuration) is coupled with a non‐chiral emissive fluorenone‐based ligand (A or B) to form a series of Pd2L2L′2 assemblies. The modular strategy allows to impart the chiral information of the helicenes to the overall supramolecular system, resulting in CPL from the non‐chiral component. Guest binding results in a 4‐fold increase of CPL intensity. The principle offers potential to generate libraries of multifunctional materials with applications in molecular recognition, enantioselective photo‐redox catalysis and information processing.

Affinity variation in the interactions of tryptophan- β-cyclodextrin-platinum complex with G-quadruplex and duplex DNAs

DNA forms non-canonical Guanine-rich-quadruplex structures that play crucial roles such as maintenance of the telomere, transcription, and replication. Selective binding of small molecular ligands to G-quadruplexes and stabilization of them gain importance in the control of cell proliferation and development of therapeutics. In this paper, we report the synthesis of a tryptophan-β-cyclodextrin complex and its platinum complex. The binding interaction of the synthesized Trp-β-CD-Pt compound with various DNAs, including a duplex DNA and three quadruplexes, are investigated. The binding of the compound to quadruplexes shows a general increase in the binding strength compared to the strength of binding with the duplex, CT-DNA. The compound reveals the strongest binding with kit22. An enhancement of fluorescence is generally observed when the ligand binds to all the DNAs, except myc22. The structure of the host: guest complex with Berberine, a model G-quadruplex binding ligand, is investigated using 2 D ROESY spectroscopy. The host: guest binding is strong and the DNA interaction does not extract much of the Berberine molecule from the complex. The differential bindings of the ligand in free- and Berberine-loaded forms with different G-quadruplexes are discussed in detail based on binding strengths and the modulation of fluorescence. Communicated by Ramaswamy H. Sarma

CASTING: A Potent Supramolecular Strategy to Cytosolically Deliver STING Agonist for Cancer Immunotherapy and SARS-CoV-2 Vaccination

CASTING: A Potent Supramolecular Strategy to Cytosolically Deliver STING Agonist for Cancer Immunotherapy and SARS-CoV-2 Vaccination

Supramolecular Self-Assembly of Porphyrin and Metallosurfactant as a Drug Nanocontainer Design.

The combined method of treating malignant neoplasms using photodynamic therapy and chemotherapy is undoubtedly a promising and highly effective treatment method. The development and establishment of photodynamic cancer therapy is closely related to the creation of sensitizers based on porphyrins. The present study is devoted to the investigation of the spectroscopic, aggregation, and solubilization properties of the supramolecular system based on 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TSPP) and lanthanum-containing surfactant (LaSurf) in an aqueous medium. The latter is a complex of lanthanum nitrate and two cationic amphiphilic molecules of 4-aza-1-hexadecylazoniabicyclo[2.2.2]octane bromide. The mixed TSPP–LaSurf complexes can spontaneously assemble into various nanostructures capable of binding the anticancer drug cisplatin. Morphological behavior, stability, and ability to drug binding of nanostructures can be tailored by varying the molar ratio and the concentration of components. The guest binding is shown to be additional factor controlling structural rearrangements and properties of the supramolecular TSPP–LaSurf complexes.

Direct Visualization of Supramolecular Binding and Separation of Light Hydrocarbons in MFM-300(In).

The purification of light olefins is one of the most important chemical separations globally and consumes large amounts of energy. Porous materials have the capability to improve the efficiency of this process by acting as solid, regenerable adsorbents. However, to develop translational systems, the underlying mechanisms of adsorption in porous materials must be fully understood. Herein, we report the adsorption and dynamic separation of C2 and C3 hydrocarbons in the metal–organic framework MFM-300(In), which exhibits excellent performance in the separation of mixtures of ethane/ethylene and propyne/propylene. Unusually selective adsorption of ethane over ethylene at low pressure is observed, resulting in selective retention of ethane from a mixture of ethylene/ethane, thus demonstrating its potential for a one-step purification of ethylene (purity > 99.9%). In situ neutron powder diffraction and inelastic neutron scattering reveal the preferred adsorption domains and host–guest binding dynamics of adsorption of C2 and C3 hydrocarbons in MFM-300(In).

‘Pincer-tweezer’ tetraimidazolium salts as hosts for halides

In this work we describe the preparation of two tetracationic molecular tweezers that were used as hosts for the recognition of chloride, bromide and iodide. These two hosts contain a rigid bis-alkynyl spacer that connects two arms built with two pincer bis-imidazolium units. The nature of the spacer confers distinct structural features to these two molecular ‘pincer-tweezers’. The tweezer with the anthracenyl linker has a quasi-parallel disposition of the two arms of the tweezer, while in the carbazolyl-linked tweezer the two arms are significantly more separated. The study of the binding affinities of these two hosts with the three target halides showed substantial differences depending on the tetra-imidazolium tweezer used. In particular, the carbazolyl-based tweezer follows a 1:2 host:guest binding model, while the binding of the anthracenyl-linked tweezer is best explained using a 1:1 model. The different behavior is ascribed to the subtle different structural features of the two tetra-azolium receptors. The comparison of the affinities of the two tetracationic hosts with the related bis-imidazolium mono-pincer host indicates significantly enhanced association constants shown by the pincer-tweezer hosts, which are ascribed to a combination of the larger electrostatic attraction provided by the use of the tetracations together with the converging orientation of the two pincer bis-imidazoliums in the structure of the tweezers. These new tweezer-shaped tetra-imidazolium receptors are significantly different to other traditional tetrazoliums used as hosts for anions, which are mostly based on cyclic and more flexible structures. The pincer-tweezer hosts are acyclic and nevertheless more rigid than most of the poly-azolium-based receptors used until now.

Pillararenes as Versatile Building Blocks for Fluorescent Materials

ConspectusFluorescent materials have received more and more attention in the past few decades because of their great potentials in the fields of luminescent devices, sensing, data storage, bioimaging, and other optical applications. Fluorescent materials comprising organic molecules are of broad interest owing to their highly tunable emission. Initial studies on organic fluorescent materials were mainly focused on the design and covalent modification of fluorophores in order to improve their photophysical properties at the molecular level, whereas in recent decades, many studies have revealed that the intermolecular or intramolecular noncovalent interactions also play a crucial role in luminescence. For example, the modulation of noncovalent interactions in aggregates and self-assemblies was proven to be capable of adjusting aggregation-induced emission (AIE)-active fluorophores by the restriction of intramolecular motions (RIM). In addition, in the crystalline state, intermolecular noncovalent interactions are able to promote phosphorescence by decreasing nonradiative decays.Introducing supramolecular macrocycles into organic fluorescent materials is an intriguing prospect because multiple noncovalent interactions are incorporated. On one hand, the photophysical properties of fluorophores can be changed upon inclusion within the macrocycles, providing unforeseen luminescence. On the other hand, the dynamic and reversible features of host–guest recognition endow the materials with controllability and stimuli-responsiveness, which is beneficial to the fabrication of smart materials. Among numerous supramolecular macrocycles, pillararenes are promising candidates that can be included in fluorescent materials. The advantages of pillararenes are their easy functionalization and planar chirality. After modification with proper substituents, pillararene derivatives possess high solubility and stability in both organic and aqueous media, and reversible guest binding remains. Such features make pillararenes versatile hosts in different environments. Additionally, pillararenes are planar chiral, and the interconversion between enantiomers can be adjusted with different-sized substituents and external stimuli, which are favorable to the construction of chiroptical materials.In this Account, we summarize research progress in the field of pillararene-based luminescent materials, which mainly includes the contributions made by our group. Using pillararenes as building blocks can facilitate the fabrication of high-performance fluorescent materials, in solution or the solid state, with different functions and mechanisms. Therefore, we categorize pillararene-based luminescent materials as those in solution or in the solid state. The applications and the advantages of pillararenes are discussed in detail. For example, in the solid state, pillararene-based host–guest complexation is capable of minimizing the aggregation-caused quenching (ACQ) of fluorophores. This broadens the application of fluorophores in crystalline materials. In solution, the host–guest complexes of pillararenes and fluorophores can self-assemble into well-defined nanostructures, which not only adjust the photophysical properties but also enable functions such as bioimaging. The remaining challenges and future perspectives are outlined at the end. It is expected that this Account will inspire new researchers in different fields and offer new opportunities for the construction of novel luminescent materials with pillararenes and other macrocycles.