Stepwise Functionalization of a Pillar[5]arene-Containing [2]Rotaxane with Pentafluorophenyl Ester Stoppers.

Detailed investigations into the stepwise bis-functionalization of a pillar[5]arene-containing rotaxane building block have been carried out. Upon a first stopper exchange, the pillar[5]arene moiety of the mono-acylated product is preferentially located close to its reactive pentafluorophenyl ester stopper, thus limiting the accessibility to the reactive carbonyl group by the nucleophilic reagents. Selective mono-functionalization is thus very efficient. Introduction of a second stopper is then possible to generate dissymmetrical rotaxanes with different amide stoppers. Moreover, when dethreading is possible upon the second acylation, the pillar[5]arene plays the role of a protecting group allowing the synthesis of dissymmetrical axles that are particularly difficult to prepare under statistical conditions. Finally, detailed conformation analysis of the rotaxanes revealed that the position of the pillar[5]arene moiety on its axle subunit is mainly governed by polar interactions in nonpolar organic solvents, whereas solvophobic effects play a major role in polar solvents.

A Visible-Light Regulated ATP Transport in Retinal-Modified Pillar[6]arene Layer-by-Layer Self-Assembled Sub-Nanochannel.

Natural light-responsive rhodopsins play a critical role in visual conversion, signal transduction, energy transmission, etc., which has aroused extensive interest in the past decade. Inspired by these gorgeous works of living beings, scientists have constructed various biomimetic light-responsive nanochannels to mimic the behaviors of rhodopsins. However, it is still challenging to build stimuli-responsive sub-nanochannels only regulated by visible light as the rhodopsins are always at the sub-nanometer level and regulated by visible light. Pillar[6]arenes have an open cavity of 6.7 Å, which can selectively recognize small organic molecules. They can be connected to ions of ammonium or carboxylate groups on the rims. Therefore, we designed and synthesized the amino and carboxyl-derived side chains of pillar[6]arenes with opposite charges. The sub-nanochannels were constructed through the electrostatic interaction of layer-by-layer self-assembled amino and carboxyl-derived pillar[6]arenes. Then, the natural chromophore of the retinal with visible light-responsive performance was modified on the upper edge of the sub-nanochannel to realize the visible light switched on and off. Finally, we successfully constructed a visible light-responsive sub-nanochannel, providing a novel method for regulating the selective transport of energy-donating molecules of ATP.

Pillar[5]arene-Based Ion-Pair Recognition for Encapsulation of a Stilbazolium-Type Dye with Enhanced Photophysical Properties and Nonlinear Optical Activity.

Constructing organic composite materials through molecular recognition has emerged as an important theme in materials science. Here we report an ion-pair recognition system involving the use of a propoxylated pillar[5]arene (PrP5) to modulate the solid-state photophysical properties of dye trans-4'-(dimethylamino)-N-methyl-4-stilbazolium hexafluorophosphate (DMASP). Single crystal X-ray diffraction analysis reveals that the dye guest DMASP is encapsulated by PrP5 to form a 2 : 1 host-guest complex 2PrP5⸧DMASP in the crystalline state. The macrocyclic skeleton of PrP5 imposes restrictions on the intramolecular motions of the dye guest, leading to a significant enhancement of its fluorescence emission. Additionally, within the 2PrP5⸧DMASP complex crystal structure, DMASP molecules are found to display two possible opposite orientations in the one-dimensional channels formed by PrP5 molecules. This arrangement is believed to alter the overall solid-state packing structure of DMASP, thereby activating its nonlinear optical activity. This work not only reports a novel ion-pair molecular recognition system based on pillararenes but also provides valuable insights into the modulation of the crystalline state photophysical properties of organic dyes via cocrystal engineering.

Integrating Pillar[5]arene and BODIPY for a Supramolecular Nanoplatform To Achieve Synergistic Photodynamic Therapy and Chemotherapy.

BODIPY photosensitizers have been integrated with a hypoxia-activated prodrug to achieve synergistic photodynamic therapy (PDT) and chemotherapy. A novel BODIPY derivative BDP-CN was designed and synthesized. It had two cyano groups to make it complex well with a water-soluble pillar[5]arene. Their association constant was calculated to be (6.8±0.9)×106  M-1 . After self-assembly in water, regular spherical nanocarriers can be formed; these were used to encapsulate the hypoxia-activated prodrug tirapazamine (TPZ). BDP-CN displayed excellent photodynamic activity to complete PDT. In this process, O2 can be continuously consumed to activate TPZ to allow it to be converted to a benzotriazinyl (BTZ) radical with high cytotoxicity to complete chemotherapy. As a result, the formed nanoparticles showed excellent synergistic photodynamic therapy and chemotherapy efficacy. The synergistic therapy mechanism is discussed in detail.

Dual-Responsive Drug-Delivery System Based on PEG-Functionalized Pillararenes Containing Disulfide and Amido Bonds for Cancer Theranostics.

The construction of a smart drug-delivery system based on amphiphilic pillararenes with multiple responsiveness properties has become an important way to improve the efficacy of tumor chemotherapy. Here, a new PEG-functionalized pillararene (EtP5-SS-PEG) containing disulfide and amido bonds was designed and synthesized, which has been used to construct a novel supramolecular nanocarrier through a host-guest interaction with a perylene diimide derivative (PDI-2NH4 ) and their supramolecular self-assembly. This nanocarrier showed good drug loading capability, and dual stimulus responsiveness to enzyme and GSH (glutathione). After loading of doxorubicin (DOX), the prepared nanodrugs displayed efficient DOX release and outstanding cancer theranostics ability.

Reply to "Where is the Macrocycle?" Correspondence on "Simultaneous Organic and Inorganic Host-guest Chemistry within Pillararene-Protein Cage Frameworks".

Our recent publication in Chem. Eur. J. 2022, 28, e202104341 has inspired Prof. Peter B. Crowley (P.C.) to write a Correspondence questioning the presented concept of electrostatic self-assembly. The offered criticism is twofold: 1) the role of the cationic pillar[5]arene macrocycle to act as molecular glue in the formation of electrostatically driven protein assemblies is questioned by arguing that the pillararene is not incorporated into the frameworks. 2) Later, P.C. speculates that when the frameworks form, the role of electrostatic interactions is not firmly established and cation-pi bonding is the more plausible interaction. In this response, the raised comments are addressed. We present direct experimental NMR evidence showing that the pillar[5]arene is incorporated into the frameworks. Furthermore, we discuss the electrostatic self-assembly and our ferritin-related research line more broadly and clarify the role of key experiments.

Pillar[5]arene-Based Fluorescent Supramolecular Polymers Without Conventional Chromophores.

Fluorescent supramolecular polymers have garnered significant attention due to their successful integration of supramolecular polymers and fluorescence, offering vast potential for applications in sensing, imaging, optoelectronics, and photonics. In this study, we present a novel supramolecular polymer based on P5-OH, derived from mono-substituted pillararene macrocycles. Notably, these formed supramolecular polymeric aggregates exhibit a prominent blue emission, representing a rare instance of fluorescent polymers devoid of conventional chromophores. Furthermore, through the modification of alkyl chain ending groups attached to pillar[5]arenes, slight shifts in the emission peak could be observed. This research expands the scope of functional supramolecular polymeric systems utilizing pillararenes, providing valuable insights for the design of innovative luminescent materials and optical devices.

Harnessing Pillar[5]arene Host-Guest Complexation To Improve pH Stability and Affect Enzymatic Degradation of the Anticancer Prodrug Capecitabine: A 19 F NMR Study.

Cancer is a global health problem, and supramolecular chemotherapy is emerging as a novel strategy to battle the disease. Here, we first evaluated the thermodynamic and kinetic stability of the complexes formed between several water-soluble per-substituted pillar[5]arene derivatives and capecitabine (1), a widely used oral chemotherapeutic prodrug. The exchange rate was studied, for the first time in pillararene chemistry, by the 19 F guest exchange saturation transfer (GEST) NMR technique. Importantly, when we evaluated the effect of complexation on the characteristics of 1, we found that the complexation of 1 with such pillar[5]arene hosts increased capecitabine stability at acidic pH very significantly and slowed its enzymatic degradation by the carboxylesterase enzyme in a manner that depended on the host. These interesting findings could have implications on the clinical use of this heavily used prodrug and might affect the management of cancer patients.

Pillararenes as Promising Carriers for Drug Delivery.

Since their discovery in 2008 by N. Ogoshi and co-authors, pillararenes (PAs) have become popular hosts for molecular recognition and supramolecular chemistry, as well as other practical applications. The most useful property of these fascinating macrocycles is their ability to accommodate reversibly guest molecules of various kinds, including drugs or drug-like molecules, in their highly ordered rigid cavity. The last two features of pillararenes are widely used in various pillararene-based molecular devices and machines, stimuli-responsive supramolecular/host-guest systems, porous/nonporous materials, organic-inorganic hybrid systems, catalysis, and, finally, drug delivery systems. In this review, the most representative and important results on using pillararenes for drug delivery systems for the last decade are presented.

Tunable Supramolecular Ag+-Host Interactions in Pillar[n]arene[m]quinones and Ensuing Specific Binding to 1-Alkynes.

We developed an improved, robust synthesis of a series of pillar[6]arenes with a varying number (0-3) of quinone moieties in the ring. This easy-to-control variation yielded a gradually less electron-rich cavity in going from zero to three quinone units, as shown from the strength of host-guest interactions with silver ions. Such macrocycle-Ag2 complexes themselves were shown to display an unprecedented, sharp distinction between terminal alkynes, which strongly bound to such complexes, and internal alkynes, internal alkenes and terminal alkenes, which do hardly bind.

Superstructure-Induced Hierarchical Assemblies for Nanoconfined Photocatalysis.

Most attempts to synthesize supramolecular nanosystems are limited to a single mechanism, often resulting in the formation of nanomaterials that lack diversity in properties. Herein, hierarchical assemblies with appropriate variety are fabricated in bulk via a superstructure-induced organic-inorganic hybrid strategy. The dynamic balance between substructures and superstructures is managed using covalent organic frameworks (COFs) and metal-organic frameworks (MOFs) as dual building blocks to regulate the performances of hierarchical assemblies. Significantly, the superstructures resulting from the controlled cascade between COFs and MOFs create highly active photocatalytic systems through multiple topologies. Our designed tandem photocatalysis can precisely and efficiently regulate the conversion rates of bioactive molecules (benzo[d]imidazoles) through competing redox pathways. Furthermore, benzo[d]imidazoles catalyzed by such supramolecular nanosystems can be isolated in yields ranging from 70 % to 93 % within tens of minutes. The multilayered structural states within the supramolecular systems demonstrate the importance of hierarchical assemblies in facilitating photocatalytic propagation and expanding the structural repertoire of supramolecular hybrids.

Supramolecular Enhancement of Charge Transport through Pillar[5]arene-Based Self-Assembled Monolayers.

Intermolecular charge transport is one of the essential modes for modulating charge transport in molecular electronic devices. Supermolecules are highly promising candidates for molecular devices because of their abundant structures and easy functionalization. Herein, we report an efficient strategy to enhance charge transport through pillar[5]arene self-assembled monolayers (SAMs) by introducing cationic guests. The current density of pillar[5]arene SAMs can be raised up to about 2.1 orders of magnitude by inserting cationic molecules into the cavity of pillar[5]arenes in SAMs. Importantly, we have also observed a positive correlation between the charge transport of pillar[5]arene-based complex SAMs and the binding affinities of the pillar[5]arene-based complexation. Such an enhancement of charge transport is attributed to the efficient host-guest interactions that stabilize the supramolecular complexes and lower the energy gaps for charge transport. This work provides a predictive pattern for the regulation of intermolecular charge transport in guiding the design of next generation switches and functional sensors in supramolecular electronics.

Gold nanoparticle functionalized nanopipette sensors for electrochemical paraquat detection.

A sensitive nanopipette sensor is established through a unique design of host-guest recognition, which could be further enhanced by the introduction of gold nanoparticles (Au NPs). Generally, the nanopipette is conjugated with caboxylatopillar[5]arenes (CP[5]) or carboxylated leaning pillar[6]arene (CLP[6]) to generate recognition sites. After the addition of pesticide molecules, they would be captured by CP[5] (or CLP[6]), resulting in a significant electronegativity change on the nanopipette's inner surface, which could be determined by the ionic current change. The CP[5]-modified nanopipette exhibited reliable selectivity for paraquat, while the CLP[6]-modified nanopipette showed an ability of detection for both paraquat and diquat. The addition of Au NPs improved the selectivity and sensitivity of the CP[5]-Au NP-modified nanopipette for paraquat sensing. After optimization by lowering the size of the Au NPs, CP[5]-Au NPs (3 nm)-modified nanopipettes achieved lower detection limits of 0.034 nM for paraquat. Furthermore, in real sample analysis, this sensor demonstrates exceptional sensitivity and selectivity. This study provides a new strategy to develop nanopipette sensors for practical small molecule detection. The gold nanoparticles enhanced quartz nanopipette sensor based on host-guest interaction was firstly established, which could achieve an excellent limit of detection of 3.4 × 10-11 mol/L for paraquat.

Synthesis of an Acidochromic and Nitroaromatic Responsive Hydrazone-Linked Pillararene Framework by a Macrocycle-To-Framework Strategy.

Tailoring the properties of solid-state organic luminescent materials using a bottom-up design principle is highly desirable for many applications. Herein, we present a "macrocycle-to-framework" strategy to construct macrocycle-functionalized and hydrazone-linked functional organic polymers with bright yellowish-green luminescence and unique solvatochromism behaviors by the condensation of a diacylhydrazine-functionalized pillar[5]arene with tris(4-formylbiphenyl)amine. Outperforming their non-macrocycle-incorporated counterparts, the pillar[5]arene-containing materials display amplified sensitivity to acidic conditions with luminescent and colorimetric dual-modal patterns assisted by the enhanced intramolecular charge transfer (ICT), and exhibit satisfactory responsiveness to nitrobenzene compounds through rapid luminescence quenching with high selectivity and a low detection limit, where the sensing process proceeds through multiple dynamic quenching pathways.

Pillararene-Induced Intramolecular Through-Space Charge Transfer and Single-Molecule White-Light Emission.

The fabrication of single-molecule white-light emission (SMWLE) materials has become a highly studied topic in recent years and through-space charge transfer (TSCT) is emerging as an important concept in this field. However, the preparation of ideal TSCT-based SMWLE materials is still a big challenge. Herein, we report a bifunctional pillar[5]arene (TPCN-P5-TPA) with a linear donor-spacer-acceptor structure and aggregation-induced emission (AIE) property. The bulky pillar[5]arene between the donor and acceptor induces a twisted conformation and a non-conjugated structure, resulting in intramolecular TSCT. In addition, the AIE feature and pillar[5]arene cavity endow TPCN-P5-TPA with responsiveness to viscosity and polar guests, by which the TSCT emission is triggered. The combination of blue locally-excited state emission and yellow TSCT emission of TPCN-P5-TPA generates SMWLE. Therefore, we provide a new and versatile strategy for the construction of TSCT-based SMWLE materials.

Symmetrically Tetra-functionalized Pillar[6]arenes Prepared by Fragment Coupling.

Due to the highly symmetrical structures generated from one-pot syntheses, the partial functionalization of macrocycles is usually beset with low yields and onerous purifications of the target multifunctional macrocycles. To improve this situation, taking pillar[6]arenes as an example, a two-step fragment coupling method has been developed for synthesizing symmetrically tetra-functionalized pillar[6]arenes, namely X-pillar[6]arenes. This method is simple and versatile, which makes hetero-fragment coupling and pre-functionalization available. Nine new macrocycles and a pillar[6]arene-based cage have been prepared. In addition, one of the newly synthesized macrocycles, COOEtEtXP[6], exhibits a strong cyan luminescence in the solid state under irradiation by 365 nm UV light. This emission originates from intramolecular through-space conjugation. Meanwhile, formation of a supramolecular polymer by multiple non-covalent intra/intermolecular interactions helps rigidify the structure and make COOEtEtXP[6] an efficient solid-state emitter. It is believed that this fragment coupling can also be used to realize the multi-functionalization of other macrocycles.

Selection of Planar Chiral Conformations between Pillar[5,6]arenes Induced by Amino Acid Derivatives in Aqueous Media.

Chiral α-amino acids play critical roles in the metabolic process in nearly all life forms. So far, chiral recognition of α-amino acids has mainly focused on the determination of l/d enantiomers. Herein, selection of planar chiral conformations between water-soluble pillar[5]arene WP5 and pillar[6]arene WP6 was observed due to α-side chain or ethyl ester moieties of l-α-amino acid ethyl ester hydrochlorides binding with WP5 and WP6, respectively. Therefore, α-side chain and ethyl ester moieties of l-α-amino acid ethyl ester hydrochlorides were recognized by observing the induced CD signal and its inversion. This is a rare example of being able to detect the chiral region around α-carbon of a chiral α-amino acid molecule.

Role of Functionalized Pillararene Architectures in Supramolecular Catalysis.

The many useful features possessed by pillararenes (PAs; e.g. rigid, capacious, and hydrophobic cavities, as well as exposed functional groups) have led to a tremendous increase in their popularity since their first discovery in 2008. In this Minireview, we emphasize the use of functionalized PAs and their assembled supramolecular materials in the field of catalysis. We aim to provide a fundamental understanding and mechanism of the role PAs play in catalytic process. The topics are subdivided into catalysis promoted by the PA rim/cavity, PA-based nanomaterials, and PA-based polymeric materials. To the best of our knowledge, this is the first overview on PA-based catalysis. This Minireview not only summarizes the fabrications and applications of PAs in catalysis but also anticipates future research efforts in applying supramolecular hosts in catalysis.

Vapochromic Behaviors of A Solid-State Supramolecular Polymer Based on Exo-Wall Complexation of Perethylated Pillar[5]arene with 1,2,4,5-Tetracyanobenzene.

The research for the solid-state supramolecular polymers with specific functions accelerates the development of supramolecular and materials sciences. Herein, we discover the different complexation modes of perethylated pillar[5]arene (EtP5) with 1,2,4,5-tetracyanobenzene (TCNB) in various solvents. Driven by charge-transfer interaction, TCNB is enclosed in the cavity of EtP5 in CHCl3 , while TCNB complexes with EtP5 at the exo-wall of EtP5 in CH2 Cl2 . This is because the size of CH2 Cl2 matches the cavity of EtP5, forcing TCNB to complex with the exo-wall of EtP5. Furthermore, we fabricate a vapochromic solid-state supramolecular polymer by exploiting the exo-wall complexation, which turns from brown to reddish brown or black after adsorption of alkyl aldehyde vapors. The adsorptive nature for alkyl aldehyde vapors comes from the unoccupied cavity of EtP5 based on C-H⋅⋅⋅π interactions. The vapochromic property is attributed to the change of the charge-transfer interaction caused by molecular rearrangement induced by vapor-capture in the solid-state supramolecular polymer.

BowtieArene: A Dual Macrocycle Exhibiting Stimuli-Responsive Fluorescence.

Although highly useful in supramolecular chemistry, pillararenes lack a fluorophore in their skeleton. Here we present BowtieArene, a novel fluorescent dual macrocycle, featuring a central tetraphenylethylene-derived fluorophore and two pillar-like, pentagon-shaped cavities which are comparable to pillar[5]arene. This concisely prepared, figure-of-eight molecule exhibits vapor absorption and host-guest capabilities, as well as intriguing switchable fluorescence. The fluorochromism of BowtieArene can be triggered by multiple external stimuli including solvent, vapor, and mechanical force, with excellent reversibility and stability. Experimental and theoretical evidence indicate that the fluorochromism should be closely related to molecular packing.