Guest Complexes Research Articles

Encapsulation of an Au25 Nanocluster inside a Porphyrin Nanoring Enhances Singlet Oxygen Generation and Photo‐Electrocatalytic CO2 Reduction

AbstractThe synthesis of molecular host–guest complexes with enhanced performance, relative to those of their components, is a central theme in supramolecular chemistry. Here we explore a host‐guest system consisting of an atomically precise gold nanocluster bound inside a zinc porphyrin nanoring. UV/Vis absorption and fluorescence titrations with different sized nanorings revealed strong binding between a pyridinethiol‐coated Au25 nanocluster and a nanoring consisting of six zinc porphyrin units, and complexation is confirmed by mass spectrometry. Formation of this assembly enhances the stability of the gold nanocluster. The host‐guest complex also exhibits remarkable activity and selectivity for photochemical CO2 to CO conversion and singlet oxygen generation.

Investigating Nanoscale Interactions of Host–Guest Complexes Formed Between CB[7] and Atenolol by Quantum Chemistry and Ultrasensitive Vibrational Spectroscopy

Investigating Nanoscale Interactions of Host–Guest Complexes Formed Between CB[7] and Atenolol by Quantum Chemistry and Ultrasensitive Vibrational Spectroscopy

Pillar[5]arene stabilized gold nanoparticles for the enhanced light-triggered nitric oxide release with antibacterial and antibiofilm activities

The reactivity of guests confined in well-defined host cavities act significantly different from that in bulk systems. In this work, pillar[5]arene not only works as a stabilizer for the fabrication of gold nanoparticles, but also act as an accelerator for the enhanced photo-triggered release of gaseous nitric oxide (NO) from encapsulated NO donor. The host–guest complex can dramatically improve the photoactivity of loaded guest molecule to generate antibacterial NO molecules through the confinement effect of pillar[5]arene cavity. The synergistic photo-triggered localized NO release and photo-thermal effect of host–guest complex demonstrated impressive antibacterial behaviors against Gram-negative bacterial strain Escherichia coli, Gram-positive bacterial strain Staphylococcus aureus and methicillin-resistant Staphylococcus aureus. Moreover, this biocompatible photo-responsive complex can also inhibit bacterial biofilm formation and disrupt the pre-existing biofilms.

Cyclodextrin-activated porphyrin-DNA nanofibers with AS1411/Hemin toehold for enhanced and targeted photodynamic therapy

Targeted photodynamic therapy is considered superior to conventional photodynamic therapy due to the enhanced uptake of photosensitizers by tumor cells. However, porphyrin-based photodynamic therapy is still limited due to the low hydrophilicity, poor biocompatibility and susceptibility to quenching of photosensitizers. Herein, we report cyclodextrin-activated porphyrin-DNA nanofibers with AS1411/Hemin toeholds, which enable targeted cancer cells recognition and catalytic oxygenation for enhanced photodynamic therapy. The nanofibers are formed through the self-assembly of the host–guest complex of cyclodextrin and porphyrin-DNA amphiphiles, and can be further functionalized on the surface with AS1411/Hemin. AS1411/Hemin can specifically target nucleolin-overexpressing cancer cells and catalyze conversion of excessive H2O2 into O2 within tumor cells, thereby alleviating tumor hypoxia and further cascaded enhancing PDT efficacy. These results suggest that the programmable and multifunctional nanofiber provided an effective nanoplatform for enhanced and targeted photodynamic therapy.

Supramolecular Polymerization of Pseudo[2]rotaxanes Formation of per‐Imidazole Pillar[5]arene‐based Host–Guest Complexations and Halogen Bonding Interactions

AbstractIn this study, we reported the construction of 3D supramolecular polymeric networks using per‐imidazole pillar[5]arene (DIMP5) as a host and 1,4‐diiodotetrafluorobenzene (L) as a halogen bond donor in chloroform. The supramolecular polymerization process was characterized by 1H NMR, 19F NMR spectroscopy, and X‐ray single crystal analysis. The C─I⋯N distance (2.78 Å) and C─I⋯N angle (177°) clearly indicated the formation of halogen bonds in the crystal structure. Meanwhile, by introducing adiponitrile (G) as the guest, a supramolecular polymerization of pseudo[2]rotaxanes was also prepared, which was driven by DIMP5‐based host–guest complexations and halogen bonding interactions.

Generation of Triplet States by Host‐Stabilized Through‐Space Conjugation for the Construction of Efficient Supramolecular Photocatalysts

AbstractPromoting the generation of triplet states is essential for developing efficient photocatalytic systems. This research presents a novel approach of host‐stabilized through‐space conjugation via the combination of covalent and non‐covalent methods. The designed building block, 4,4′‐(1,4(1,4)‐dibenzene cyclohexaphane‐1,4‐diyl)bis(1‐phenylpyridinium) chloride, features inherently stable through‐space conjugation. When this block forms a 1 : 1 host–guest complex with cucurbit[8]uril, the through‐space conjugation is further stabilized within the confined cavity. Both the generation and lifetime of triplet state are significantly increased, resulting from the host‐stabilized through‐space conjugation. Additionally, the ultrahigh binding constant of 6.58×1014 M−1 ensures the persistence of host‐stabilization effect. As a result, the host–guest complex acts as a highly efficient catalyst in the photocatalytic oxidation of thioether and aromatic alcohol. In the photodegradation of lignin, a complex natural product, the host–guest complex also exhibits high efficiency, demonstrating its robustness. This line of research is anticipated to enrich the toolbox of supramolecular photochemistry and provide a strategy for fabricating efficient supramolecular photocatalysts.

Color-Tunable Thermally Activated Delayed Fluorescence Polymeric Materials Constructed by Host–Guest Complexation Revealing Rewritable Advanced Information Encryption

Color-Tunable Thermally Activated Delayed Fluorescence Polymeric Materials Constructed by Host–Guest Complexation Revealing Rewritable Advanced Information Encryption

A Double‐walled Noncovalent Carbon Nanotube by Columnar Packing of Nanotube Fragments

Herein, we report the synthesis of double‐walled noncovalent carbon nanotubes (CNTs) through host–guest complexation of nanotube fragments and tube‐forming crystal engineering. As the smallest fragment of double‐walled CNTs, a host–guest complex of perfluorocycloparaphenylene (PFCPP) and carbon nanobelt (CNB) was synthesized by mixing them in solvents. The immediate complexation of the PF[12]CPP⊃(6,6)CNB complex with a remarkably high association constant (Ka) of 2×105 L/mol was observed. Time‐dependent 1H NMR and thermogravimetry measurements revealed that the stability of (6,6)CNB was significantly improved by encapsulation. X‐ray crystallography confirmed the robust belt‐in‐ring structure of this complex. As indicated by the short distance between PF[12]CPP and (6,6)CNB (2.8 Å), intermolecular orbital interactions exist between the belt and the ring, which were further supported by theoretical calculation and phosphorescence quenching experiments. While the PF[12]CPP⊃(6,6)CNB complex adopts various crystal packing structures, chloroform was discovered to be a magic “glue” solvent inducing one‐dimensional alignment of the PF[12]CPP⊃(6,6)CNB complex to build an unprecedented double‐walled noncovalent CNT structure.

A combination of covalent and noncovalent restricted‐intramolecular‐rotation strategy for supramolecular AIE‐type photosensitizer toward photodynamic therapy

AbstractPhotodynamic therapy (PDT) is a promising noninvasive method for targeted cancer cell destruction. Still, its effectiveness is often hindered by the aggregation‐caused quenching effect of organic photosensitizer (PS) in aqueous environments. Here, we have employed a combination of covalent and noncovalent restricted‐intramolecular‐rotation strategies to develop supramolecular PSs with aggregation‐induced emission (AIE) characteristics. Firstly, a water‐soluble octacationic molecular cage (1) with a bilayer tetraphenylethene (TPE) structure has been designed and synthesized, which minimizes intramolecular rotation of TPE moieties and achieves the single‐molecule‐level aggregation by the covalent restriction of intramolecular rotation (RIR) via molecular engineering synthesis. Compared with its single‐layer TPE analog, 1 exhibits superior efficiency in generating reactive oxygen species (ROS) including superoxide radical (O2−•) and singlet oxygen (1O2) upon white‐light irradiation. Subsequently, by forming a 1:4 host–guest complex (1@CB[8]4) between 1 and cucurbit[8]uril (CB[8]), O2−• generation can be further enhanced by the noncovalent RIR via the host–guest assembly. Additionally, 1@CB[8]4 as a photocatalyst promotes rapid oxidation of nicotinamide adenine dinucleotide (NADH) in water. Given its Type‐I ROS generation and catalytic activity for NADH oxidation, 1@CB[8]4 acts as a supramolecular AIE‐type PS to exhibit strong photo‐induced cytotoxicity upon white‐light irradiation under hypoxic conditions, showcasing its potential for synergistic PDT.

Nature of host–guest interaction of cyclic alcohols in β-Cyclodextrin: A molecular view of its structural features

Host- guest complexes are commonly found in several disciplines such as biochemistry, cosmetics, food, pharmaceuticals, and the environment. Studying the relationships between host and guest is essential in this context to understand their physicochemical behavior. This study aimed to examine the intermolecular interactions of cyclic alcohols within β-cyclodextrin (β-CD). The experimental spectroscopic results demonstrated the formation of the studied complexes. In this work, two orientations were used: orientation A (hydroxyl group toward the primary hydroxyl of β-CD) and orientation B (hydroxyl group toward the secondary hydroxyl of β-CD). The results indicate that regardless of the orientation used, the profile energy is thermodynamically favorable. However, there are differences in terms of greater or less stability in terms of the thermodynamic parameters studied. Physicochemical properties demonstrate that the host–guest complex forms spontaneously, and exothermic mode. The interaction between cyclic alcohols and β-CD in orientation A promotes a more pronounced deformation of the secondary edge of β-CD. Moreover, the arrangement of moleculesdemonstrates that intramolecular hydrogen bonds are less stable between the glycosidic units of β-CD. This arrangement may help or hinder the development of intermolecular hydrogen bonds.

Unusual Metal–organic Multicomponent Ni(II) and Mononuclear Zn(II) Compounds Involving Pyridine dicarboxylates: Supramolecular Assemblies and Theoretical Studies

In the present work, we reported the synthesis and characterization [single crystal X-ray diffraction technique, spectroscopic, etc.] of two new Ni(II) and Zn(II) coordination compounds, viz. [Ni(2,6-PDC)2]2[Ni(en)2(H2O)2]2[Ni(en)(H2O)4]·4H2O (1) and [Zn(2,6-PDC)(Hdmpz)2] (2) (where 2,6-PDC = 2,6-pyridinedicarboxylate, en = ethylene-1,2-diamine, and Hdmpz = 3,5-dimethyl pyrazole). Compound 1 is found to crystallize as a multicomponent Ni(II) compound with five discrete complex moieties, whereas compound 2 is isolated as a mononuclear Zn(II) compound. A deep analysis of the crystal structure of 1 unfolds unusual dual enclathration of guest complex cationic moieties within the supramolecular host cavity stabilized by anion–π, π-stacking, N–H⋯O, C–H⋯O, and O–H⋯O hydrogen bonding interactions. Again, the crystal structure of compound 2 is stabilized by the presence of unconventional C–H⋯π(chelate ring) interactions along with C–H⋯O, C–H⋯N hydrogen bonding, π-stacking, and C–H⋯π(pyridyl) interactions. These non-covalent interactions were further studied theoretically using density functional theory (DFT) calculations, molecular electrostatic potential (MEP) surfaces, non-covalent interaction (NCI) plot index, and quantum theory of atoms in molecules (QTAIM) computational tools. The computational study displays that π-stacking or H bonds greatly tune the directionality of compound 1, although non-directional electrostatic forces dominate energetically. For compound 2, a combined QTAIM/NCI plot analysis confirms the presence of unconventional C–H⋯π(chelate ring) interactions along with other weak interactions obtained from the crystal structure analysis. Further, the individual energy contributions of these weak yet significant non-covalent interactions have also been determined computationally.

Light-Controlled Interconvertible Self-Assembly of Non-Photoresponsive Suprastructures

Achieving light-induced manipulation of controlled self-assembly in nanosized structures is essential for developing artificially dynamic smart materials. Herein, we demonstrate an approach using a non-photoresponsive hydrogen-bonded (H-bonded) macrocycle to control the self-assembly and disassembly of nanostructures in response to light. The present system comprises a photoacid (merocyanine, 1-MEH), a pseudorotaxane formed by two H-bonded macrocycles, dipyridinyl acetylene, and zinc ions. The operation of such a system is examined according to the alternation of self-assembly through proton transfer, which is mediated by the photoacid upon exposure to visible light. The host–guest complexation between the macrocycle and bipyridium guests was investigated by NMR spectroscopy, and one of the guests with the highest affinity for the ring was selected for use as one of the components of the system, which forms the host–guest complex with the ring in a 2:1 stoichiometry. In solution, a dipyridine and the ring, having no interaction with each other, rapidly form a complex in the presence of 1-MEH when exposed to light and thermally relax back to the free ring without entrapped guests after 4 h. Furthermore, the addition of zinc ions to the solution above leads to the formation of a polypseudorotaxane with its morphology responsive to photoirradiation. This work exemplifies the light-controlled alteration of self-assembly in non-photoresponsive systems based on interactions between the guest and the H-bonded macrocycle in the presence of a photoacid.

Host–Guest Complexations of a Diastereoisomeric Mixture of cis- and trans-1,4-Bis(diphenylhydroxymethyl)cyclohexane in Pyridine and Methylpyridine Solutions: Significant Inclusion Selectivities and an Uncommon Host Conformation

Host–Guest Complexations of a Diastereoisomeric Mixture of <i>cis-</i> and <i>trans</i>-1,4-Bis(diphenylhydroxymethyl)cyclohexane in Pyridine and Methylpyridine Solutions: Significant Inclusion Selectivities and an Uncommon Host Conformation

Ring‐Size Control and Guest‐Induced Circularly Polarized Luminescence in Heteroleptic Pd3A3B3 and Pd4A4B4 Assemblies

AbstractTwo new structural motifs within the class of heteroleptic PdnAnBn assemblies, namely syn‐cis‐Pd3A3B3 bowls and bowl‐ (syn) or saddle‐ (anti) shaped cis‐Pd4A4B4 rings are introduced. All of the ten examples share a common longer fluorenone‐based bis‐monodentate ligand, equipped with meta‐pyridine donor groups. The ring size (3‐ vs. 4‐membered) and conformational preference (bowl vs. saddle) are controlled by the choice of the shorter ligand. These carry para‐pyridine donors, different aromatic backbones (benzene, thiophene or selenophene) and either no or small or bulky endohedral substituents, serving to control the nuclearity of the heteroleptic rings through different effects (ligand angle, charge distribution or backbone bulk). Moreover, the luminescence of the fluorenone ligand is conserved in the formed architectures. Emission intensity as well as host–guest properties vary depending on the inward‐pointing functions. All Pd3A3B3 assemblies are shown to bind chiral guest BINOL bis‐sulfonate which imparts its chirality to the entire host–guest complex. This results in a guest‐induced circular dichroism (CD) and circularly polarized luminescence (CPL) with dissymmetry factor glum up to 10−3.

Manifold Fluorescence Enhancement of a Styryl(pyridinium)-chromene Hybrid Dye upon Binding with an Elongated β-Cyclodextrin Cavity.

The interaction of a styryl(pyridinium)-chromene hybrid dye (DSP-C) with the 2-hydroxypropyl-β-cyclodextrin (HPβCD) macrocycle leads to a remarkably large increase (∼310-fold) in its fluorescence intensity, in contrast to the relatively smaller (∼45-fold) enhancement observed with native β-cyclodextrin (βCD). Both macrocycles (βCD and HPβCD) bind with the styryl(pyridinium) as well as the chromene fragments of the hybrid dye, with the simultaneous formation of 1:1 and 2:1 host:guest complexes. However, the binding constant (Keq1) is more than an order of magnitude higher for HPβCD than for βCD. The improved binding affinity of HPβCD is attributed to its elongated and deeper hydrophobic cavity. This is supported well by the optimized geometries of the host-guest complexes. Theoretical calculations also reveal that the energy change due to the release of high-energy water molecules from the host nanocavity is more favorable for HPβCD than βCD, resulting in greater stability of the HPβCD:DSP-C complex. Interestingly, though the fluorescence of DSP-C arises from its styryl(pyridinium) fragment, the complexation of the chromene unit with the host plays a major role in augmenting the fluorescence enhancement of the hybrid dye. The large fluorescence change in the HPβCD:DSP-C system has been utilized for the detection of bile salts by the indicator displacement strategy.

Ligand‐Directed Synthesis of a Self‐Organized Chloro‐Bridged Cubic Pd(II) Cage Showing Selective Encapsulation of Phenols

AbstractThe synthesis and guest recognition properties of a neutral Pd24‐cubic cage, [{Pd3(NiPr)3PO}8(μ2‐Cl)24] 1 are reported. The formation of the cubical assembly takes place by an exclusive one‐pot ligand‐assisted pathway directed by an oximido linker. The initial coordination of the oximido ligand pre‐organizes the [Pd3(NiPr)3PO]3+ polyhedral building units into a tetrameric intermediate, which then transforms into an oximido‐tethered tetrahedral assembly and to the cubical cage 1 in the presence of chloride ions. In the absence of the directing oximido linker, no cage formation was observed, and the Pd6‐precursor was found to undergo self‐condensation, giving rise to a new pentameric polyhedral cluster, [Pd5{(NiPr)3PO}2(OAc)2(OH)2] 2. The central cavity of the cube has been probed for guest encapsulation studies, which shows a high binding with phenolic guest molecules with association constants of the order of 104–105 M−1. The favorable formation of host–guest complexes was attributed to the strong hydrogen bonding interactions between the host and guest functional groups.

A Bis(Acridino)-Crown Ether for Recognizing Oligoamines in Spermine Biosynthesis.

Oligoamines in cellular metabolism carry extremely diverse biological functions (i.e., regulating Ca2+-influx, neuronal nitric oxide synthase, membrane potential, Na+, K+-ATPase activity in synaptosomes, etc.). Furthermore, they also act as longevity agents and have a determinative role in autophagy, cell growth, proliferation, and death, while oligoamines dysregulation is a key in a variety of cancers. However, many of their mechanisms of actions have just begun to be understood. In addition to the numerous biosensing methods, only a very few simple small molecule-based tests are available for their selective but reversible tracking or fluorescent labeling. Motivated by this, we present herein a new fluorescent bis(acridino)-crown ether as a sensor molecule for biogenic oligoamines. The sensor molecule can selectively distinguish oligoamines from aliphatic mono- and diamino-analogues, while showing a reversible 1:2 (host:guest) complexation with a stepwise binding process accompanied by a turn-on fluorescence response. Both computational simulations on molecular docking and regression methods on titration experiments were carried out to reveal the oligoamine-recognition properties of the sensor molecule. The new fluorescent chemosensor molecule has a high potential for molecular-level functional studies on the oligoamine systems in cell processes (cellular uptake, transport, progression in cancers, etc.).

Supramolecular Chemistry of Polymer-Based Molecular Tweezers: A Minireview

Polymer-based molecular tweezers have emerged as a prominent research area due to their enhanced ability to form host–guest complexes, driven by advancements in their design and synthesis. The impact of the spacer structure on the tweezers is predominant. They can be rigid, flexible, and stimuli-responsive. Herein, a new generation of molecular tweezers is introduced as polymer-based molecular tweezers. The integration of molecular tweezers onto biopolymers has significantly expanded their potential applications, making them promising candidates, especially in drug delivery, owing to their biocompatibility, adaptive structural features, and versatile interaction capabilities. The unique structure of polymer-based molecular tweezers, particularly when integrated with biopolymers, creates a unique nano-environment that enhances their interaction with guest molecules. This minireview focuses on the synthesis and applications of polymer-based molecular tweezers and examines how the incorporation of various spacers affects their binding affinity and specificity. These features highlight the advancement of these polymer-based systems, emphasizing their potential applications, particularly in drug delivery, water treatment technology, and future research opportunities.

In situ self-assembly of artesunate-β-cyclodextrin supramolecular nanomedicine as potential anti-cancer prodrug

Supramolecular nanomedicines have drawn great interest in cancer therapy, but their potential immunotoxicities restrict application in clinical translation. Herein, we constructed a supramolecular nanomedicine CD-Artesunate (CD-ATS) in situ by supramolecular polymerization and orthogonal self-assembly. The nanostructure was meticulously characterized using 1D and 2D Nuclear Magnetic Resonance (NMR) spectroscopy, Mass spectrometry, Transmission Electron Microscopy (TEM), and particle size distribution analysis. β-cyclodextrin (β-CD) hosts are conjugated with artesunate (ATS) by click chemistry to improve the solubility and antitumor activity of ATS. Supramolecular nanomedicine was prepared through orthogonal self-assembly driven by host−guest complexation and hydrogen bonds. The results showed that the aqueous solubility of CD-ATS was 30 times better than that of free ATS. Furthermore, CD-ATS displayed a superior antitumor effect against HCT116 tumor cells compared to the first-line drug Taxol. This enhanced effect was attributed to the induction of excessive reactive oxygen species (ROS) generation, which subsequently triggered apoptosis.

2,3 : 6,7‐Naphthalene Bis(dicarboximide) Cyclophane: A Photofunctional Host for Ambient Delayed Fluorescence in Solution

AbstractHarvesting triplet excitons of heavy atom‐free purely organic chromophores under aerated conditions is challenging due to the quenching of long‐lived triplet states by molecular oxygen and vibrational dissipation. Herein, we show a supramolecular approach of triplet harvesting via mitigating quenching pathways of a triplet harvester. Specifically, we used a host–guest system based on 2,3 : 6,7‐naphthalene bis(dicarboximide)‐derived cyclophane (NBICy) and carbazole derivative (EtCz). Complexation studies and single‐crystal X‐ray analysis showed the formation of a rigid host–guest complex (K≈104 M−1 in CCl4), resulting in triplet‐exciton stabilization under aerated conditions via mitigating vibrational interference and oxygen quenching. Photophysical studies elucidate the delayed fluorescence emission from the charge‐transfer state (1CT) with a quantum yield (QY) of 6–8 % under ambient conditions which increased up to 36 % in an inert atmosphere.