Self-Assembled Nanohelixes Driven by Host-Guest Interactions and Metal Coordination.

Helical nanostructures fabricated via the self-assembly of artificial motifs have been a captivating subject because of their structural aesthetics and multiple functionalities. Herein, we report the facile construction of a self-assembled nanohelix (NH) by leveraging an achiral aggregation-induced emission (AIE) luminogen (G) and pillar[5]arene (H), driven by host-guest interactions and metal coordination. Inspired by the "sergeants and soldiers" effect and "majority rule" principle, the host-guest complexation between G and H is employed to fixate the twisted conformation of G for the generation of "contortion sites", which further induced the emergence of helicity as the 1D assemblies are formed via Ag(I) coordination and hexagonally packed into nano-sized fibers. The strategy has proved feasible in both homogeneous and heterogeneous syntheses. Along with the formation of NH, boosted luminescence and enhanced productivity of reactive oxygen species (ROS) are afforded because of the efficient restriction on G, indicating the concurrent regulation of NH's morphology and photophysical properties by supramolecular assembly. In addition, NH also exhibits the capacity for bacteria imaging and photodynamic antibacterial activities against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli).

Pillar[n]arene-Based Fluorescence Turn-On Chemosensors for the Detection of Spermine, Spermidine, and Cadaverine in Saline Media and Biofluids.

Polyamines are essential analytes due to their critical role in various biological processes and human health in general. Due to their role as regulators for cell growth and proliferation (putrescine and spermine), as neuroprotectors, gero-, and cardiovascular protectors (spermidine), and as bacterial growth indicators (cadaverine), rapid, simple, and cost-effective methods for polyamine detection in biofluids are in demand. The present study focuses on the development and investigation of self-assembled and fluorescent host⋅dye chemo-sensors based on sulfonated pillar[5]arene for the specific detection of polyamines. Binding studies, as well as stability and functionality assessments of the turn-on chemosensors for selective polyamine detection in saline and biologically relevant media, are shown. Furthermore, the practical applicability of the developed chemo-sensors is demonstrated in biofluids such as human urine and saliva.

High-resolution performance of pillar[6]arene functionalized with imidazolium ionic liquids for gas chromatography.

Pillar[n]arenes (P[n]A, n = 5-10) have attracted much attention because of their highly symmetric pillar-shaped architecture with π-electron rich cavity. Nevertheless, the use of ionic liquid functionalized P[n]A in chromatography has not been reported up to data. This work reports the investigation of the imidazolium ionic liquids functionalized pillar[6]arene (P6A-C10-IM-C8[NTf2]) as the stationary phase for gas chromatography (GC). The statically coated P6A-C10-IM-C8[NTf2] column (0.25 mm i.d.) showed moderate polarity and high column efficiency of 4733 plates/m determined by n-dodecane at 120 °C (k = 2.29). Owing to its unique amphiphilic conformation, the P6A-C10-IM-C8[NTf2] showed good column inertness and resolving capability for a wide range of analytes and isomers. Particularly, the P6A-C10-IM-C8[NTf2] column exhibited distinctly advantageous performance for the challenging isomers of halogenated benzenes, benzaldehydes, phenols and anilines over the common commercial columns, namely 5% phenyl methyl polysiloxane (HP-5) and 35% phenyl methyl polysiloxane (HP-35). In addition, it exhibited good column repeatability and reproducibility with RSD values on the retention times less than 0.05% for run-to-run, 0.38% for day-to-day and 2.94% for column-to-column, respectively. This work demonstrates the promising future of ionic liquid P[n]A stationary phases for chromatographic separations.

Regulation of Fluorescence and Self-assembly of a Salicylaldehyde Azine-Containing Amphiphile by Pillararene.

Regulation of fluorescence and self-assembly of a salicylaldehyde azine-containing amphiphile by a water-soluble pillar[5]arene via host-guest recognition in water was realized. The fluorescence and the self-assembled aggregates of the bola-type amphiphile G can be tailored by adding different amounts of water-soluble pillar[5]arene (WP5). In addition, the emission property and self-assembly behavior of G and WP5 are responsive to pH conditions. Furthermore, the fluorescence emission property of G and the regulation by WP5 or pH conditions was applied as information encryption material, rewritable paper, and erasable ink. We believe that this fluorescence regulation strategy is promising for the construction of advanced fluorescent organic materials.

Delving into the Variability of Supramolecular Affinity: Self-Ion Pairing as a Central Player in Aqueous Host-Guest Chemistry.

The determination of binding constants is a key matter in evaluating the strength of host-guest interactions. However, the profound impact of self-ion pairing on this parameter is often underrated in aqueous solution, leading in some cases to a misinterpretation of the true potential of supramolecular assemblies. In the present study, we aim to shed further light on this critical factor by exploring the concentration-dependent behavior of a multicharged pillararene in water. Our observations reveal an extraordinary 1-million-fold variability in the affinity of this macrocycle toward a given anion, showcasing the highly dynamic character of electrostatic interactions. We argue that these findings bring to the forefront the inherent determinism that underlies the estimation of affinity constants, a factor profoundly shaped by both the sensitivity of the instrumental technique in use and the intricacies of the experimental design itself. In terms of applications, these results may provide the opportunity to optimize the operational concentrations of multicharged hosts in different scenarios, aiming to achieve their maximum efficiency based on the intended application. Unlocking the potential of this hidden variability may pave the way for the creation of novel molecular materials with advanced functionalities.

The Synthesis and Antibacterial Properties of Pillar[5]arene with Streptocide Fragments.

The growing problem of bacterial resistance to antimicrobials actualizes the development of new approaches to solve this challenge. Supramolecular chemistry tools can overcome the limited bacterial resistance and side effects of classical sulfonamides that hinder their use in therapy. Here, we synthesized a number of pillar[5]arenes functionalized with different substituents, determined their ability to self-association using DLS, and characterized antimicrobial properties against S. typhimurium, K. pneumoniae, P. aeruginosa, S. epidermidis, S. aureus via a resazurin test. Biofilm prevention concentration was calculated for an agent with established antimicrobial activity by the crystal-violet staining method. We evaluated the mutagenicity of the macrocycle using the Ames test and its ability to affect the viability of A549 and LEK cells in the MTT-test. It was shown that macrocycle functionalized with sulfonamide residues exhibited antimicrobial activity an order higher than pure streptocide and also revealed the ability to prevent biofilm formation of S. aureus and P. aeruginosa. The compound did not show mutagenic activity and exhibited low toxicity to eukaryotic cells. The obtained results allow considering modification of the macrocyclic platforms with classic antimicrobials as an opportunity to give them a "second life" and return to practice with improved properties.

Crystal structure and supra-molecular features of a bis-urea-functionalized pillar[5]arene.

The crystal structure of a bis-urea derivative based on A1/A2-functionalized pillar[5]arene (DUP) that encapsulates dimethyl formamide (DMF) inside the macrocyclic cavity is reported. The crystal structure of DUP·DMF, C63H70N4O12·C3H7NO, reveals that out of two urea functionalized spacers, one arm is oriented above the macrocyclic cavity with strong hydrogen-bonding inter-actions between the urea H atoms and DMF guest, whereas, the other arm is positioned away from the macrocycle, leading to inter-molecular hydrogen-bonding inter-actions between the urea H atoms of two adjacent pillar[5]arene macrocycles, resulting in the formation of a supra-molecular dimer.

Host-Guest-Interaction Enhanced Nitric Oxide Photo-Generation within a Pillar[5]arene Cavity for Antibacterial Gas Therapy.

Supramolecular macrocycles with intrinsic cavities have been widely explored as containers to fabricate versatile functional materials via specific host-guest recognitions. However, relatively few studies have focused on the modulation of guest reactivity within a macrocyclic cavity. Here, we demonstrate the confinement effect of pillar[5]arene with an electron-rich and precise cavity that can dramatically enhance guest photoactivity and nitric oxide (NO) generation upon visible light irradiation. Mechanism studies reveal that it is achieved through increasing the ground state nitro-aromatic torsion angle, suppressing the intersystem crossing relaxation path of the S1 state, and accelerating the isomerization reaction path of guest molecules. This NO-generating system displays broad-spectrum antibacterial, biofilm inhibition, and dispersal activities. Moreover, it can accelerate the healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in vivo.

Porous pillararene-based polymer as adsorbent and solid disinfectant for water treatment.

Pillararene polymers have been widely used as excellent adsorbents for water treatment, but pillararene polymers with ultra-high specific surface area and versatility are still rarely reported. Herein, a quaternary ammonium salt modified pillar [5] arene polymer, QPBP [5], with specific surface area of 1844 m2 g-1 was successfully synthesized. Since QPBP [5] has abundant different adsorption sites, it exhibits excellent performance for the simultaneously removal of organic pollutants with different charges from water. The selected three model pollutants, Rhodamine B (RhB, positively charged), Sulfamethazine (SMT, electrically neutral) and Fulvic acid (FA, negatively charged), could be rapidly and efficiently removed from water by QPBP [5] within 10 min, which are much faster than them by most of the reported adsorbents. RhB and SMT are mainly adsorbed through hydrophobic interactions with the QPBP [5] surface, while FA is mainly removed through ion exchange. In addition, QPBP [5] also showed excellent reusability and adsorption performance for the environmentally relevant concentration of pollutants. Furthermore, the quaternary ammonium groups on QPBP [5] makes it a solid disinfectant with excellent antibacterial properties. In conclusion, QPBP [5] is a promising multifunctional adsorbent for the treatment of complex pollutants in water.

Highly Selective Transport and Enrichment of Lithium Ions through Bionic Ion Pair Receptor Nanochannels.

Inspired by ion pair cotransport channels in biological systems, a bionic nanochannel modified with lithium ion pair receptors is constructed for selective transport and enrichment of lithium ions (Li+). NH2-pillar[5]arene (NP5) is chosen as ion pair receptors, and the theoretical simulation and NMR titration experiments illustrate that NP5 has good affinity for the ion pair of LiCl through a strong host-guest interaction at the molecular level. Due to the confinement effect and ion pair cooperation recognition, an NP5-based receptor was introduced into an artificial PET nanochannel. An I-V test indicated that the NP5 channel realized the highly selective recognition for Li+. Meanwhile, transmembrane transport and COMSOL simulation experiments proved that the NP5 channel achieved the transport and enrichment of Li+ through the cooperative interaction between NP5 and LiCl. Moreover, the receptor solution of transmembrane transport LiCl in the NP5 channel was used to cultivate wheat seedlings, which obviously promoted their growth. This nanochannel based on the ion pair recognition will be much useful for practical applications like metal ion extraction, enrichment, and recycle.

Multifunctional Supramolecular Vesicles as Zn2+ -Triggered Microglial Modulator Alleviates Alzheimer's Disease.

Zn2+ -induced ß-amyloid protein (Aß) aggregation and microglia activation are the predominant contributors in Alzheimer's disease (AD). Regulating intracephalic excessive Zn2+ is a promising therapeutic strategy for AD treatment. However, only inhibition of Zn2+ is hardly to repair continuous damages caused by activated microglia. Herein, an intelligent resveratrol-loaded supramolecular vesicles (RES-loaded vesicles) with zinc ion chelation function and responsive release capability are constructed to alleviate Aß fibrillation, oxidative stress, and microglial dysfunction. The resveratrol encapsulation efficiency and drug loading efficiency are calculated to be 49.67% and 7.87%, respectively. In vitro studies demonstrate that the RES-loaded vesicles can modulate Zn2+ -dependent Aß aggregation. More importantly, the cargoes will be released in zinc environment and further reprograms microglia from proinflammatory M1 phenotype toward anti-inflammatory M2 phenotype, which prevents spontaneous neuroinflammation and alleviates cytotoxicity of cultured cells from 29% to 12%. With the stereotactic or intranasal administration, RES-loaded vesicles can overcome the blood brain barrier, alleviate neuronal apoptosis, neuroinflammation, and ultimately ameliorate cognitive impairment in two AD mouse models. This work provides a new sight for taking advantage of Zn2+ to treat CNS disorders.

Pillararene-Based Supramolecular Polymers for Cancer Therapy.

Supramolecular polymers have attracted considerable interest due to their intriguing features and functions. The dynamic reversibility of noncovalent interactions endows supramolecular polymers with tunable physicochemical properties, self-healing, and externally stimulated responses. Among them, pillararene-based supramolecular polymers show great potential for biomedical applications due to their fascinating host-guest interactions and easy modification. Herein, we summarize the state of the art of pillararene-based supramolecular polymers for cancer therapy and illustrate its developmental trend and future perspective.

Macrocycle-Strutted Coordination Microparticles for Fluorescence-Monitored Photosensitization and Substrate-Selective Photocatalytic Degradation.

The prosperous advancement of supramolecular chemistry has motivated us to construct supramolecular hybrid materials with integrated functionalities. Herein, we report an innovative type of macrocycle-strutted coordination microparticle (MSCM) using pillararenes as the struts and "pockets", which performs unique activities of fluorescence-monitored photosensitization and substrate-selective photocatalytic degradation. Prepared via a convenient one-step solvothermal method, MSCM showcases the incorporation of supramolecular hybridization and macrocycles, endowed with well-ordered spherical architectures, superior photophysical properties, and photosensitizing capacity, where a self-reporting fluorescence response is exhibited upon photoinduced generation of multiple reactive oxygen species. Importantly, photocatalytic behaviors of MSCM show marked divergence toward three different substrates and reveal pronounced substrate-selective catalytic mechanisms, attributing to the variety in the affinity of substrates toward MSCM surfaces and pillararene cavities. This study brings new insight into the design of supramolecular hybrid systems with integrated properties and further exploration of functional macrocycle-based materials.

Separation of Low-Molecular-Weight Organics by Water-Soluble Macrocyclic Arenes.

In this study, we fabricate a series of water-soluble anionic macrocyclic arenes, including pillar[5]arene (WP5), pillar[6]arene (WP6), leaning pillar[6]arene (WLT6), and biphenyl-extended pillar[6]arene (WBpP6), which show different separation capabilities toward low-molecular-weight organics, such as short chain haloalkanes, cyclic aliphatics, and aromatics, in water. The liquid-liquid distribution experiments are carried out at room temperature. The separation factor for low-molecular-weight organics is evaluated in the extraction of equimolar mixtures. WP6 demonstrates a high extraction efficiency of up to 89% in separating toluene/methylcyclohexane mixtures. These adsorbents also have the advantages of rapid adsorption, high separation efficiency, remarkable selectivity, and good recyclability. This work not only expands the application scope of macrocyclic chemistry, but also has practical research value for organics separation and water purification.

Supramolecular Combination Cancer Therapy Based on Macrocyclic Supramolecular Materials.

Supramolecular combination therapy adopts supramolecular materials to design intelligent drug delivery systems with different strategies for cancer treatments. Thereinto, macrocyclic supramolecular materials play a crucial role in encapsulating anticancer drugs to improve anticancer efficiency and decrease toxicity towards normal tissue by host-guest interaction. In general, chemotherapy is still common therapy for solid tumors in clinics. However, supramolecular combination therapy can overcome the limitations of the traditional single-drug chemotherapy in the laboratory findings. In this review, we summarized the combination chemotherapy, photothermal chemotherapy, and gene chemotherapy based on macrocyclic supramolecular materials. Finally, the application prospects in supramolecular combination therapy are discussed.

A Water-Soluble Leggero Pillar[5]arene.

The study of aqueous-phase molecular recognition of artificial receptors is one of the frontiers in supramolecular chemistry since most biochemical processes and reactions take place in an aqueous medium and heavily rely on it. In this work, a water-soluble version of leggero pillar[5]arene bearing eight positively charged pyridinium moieties (CWP[5]L) was designed and synthesized, which exhibited good binding affinities with certain aliphatic sulfonate species in aqueous solutions. Significantly, control experiments demonstrate that the guest binding performance of CWP[5]L is superior to its counterpart water-soluble macrocyclic receptor in traditional pillararenes.

Pillararene-Based Supramolecular Vesicles for Stimuli-Responsive Drug Delivery.

Supramolecular vesicles (SMVs) self-assembled from the supra-amphiphiles, consisting of two scaffolds linked together through noncovalent interactions, can realize stimuli-responsive controlled release of encapsulated drugs for enhanced therapeutic efficacy and minimized side effect of drugs. Pillararenes (PAs), an emerging kind of macrocyclic hosts in 2008, are easy to modify with a variety of functionalities. SMVs from PAs and specific guests mainly based on the host-guest interactions have attracted increasing attention because of their drug delivery and controlled drug release. A great progress in the construction and stimuli-responsive drug delivery of the PA-based SMVs has been made since the first work was reported in 2012. This review summarizes the major achievements of the PA-based SMVs for stimuli-responsive drug delivery over the past 5 years, including the microstructures of SMVs, multiple stimuli-responsive SMVs, prodrug SMVs from prodrug PAs and guests, bola-type SMVs, multifunctional SMVs, glucose-responsive SMVs for insulin delivery, novel SMVs from responsive PAs, thermo-responsive SMVs, and ternary SMVs, for chemotherapy, photothermal therapy, photodynamic therapy, and other biological applications. The future challenges and research directions of PA-based SMVs are also outlined from the points of views of the fundamental research, biological applications, and clinical applications of PA-based SMVs.

New Synthetic Route to Water-Soluble Prism[5]arene Hosts and Their Molecular Recognition Properties.

We report that the direct macrocyclization of naphthalene monomers bearing ethyl ester functional groups delivers prism[5]arene derivatives, which can be deprotected to yield water-soluble prism[5]arenes (H1 and H3). 1 H NMR spectroscopy showed that dicationic guests bind with the hydrophobic cores buried inside the anisotropic magnetically shielding cavity. Isothermal titration calorimetry measurements showed that H1 and H3 are high-affinity hosts in PBS-buffered water with Ka values exceeding 109  M-1 for a select guest. The complexation events are driven by the non-classical hydrophobic effect, CH⋅⋅⋅π interactions, and electrostatic interactions. Host H1 displays somewhat higher affinity toward a common guest than pillar[6]arene bearing carboxylic acid functional groups but is significantly less potent than pillar[6]arene bearing sulfate groups. H1 and H3 should be considered alongside other high affinity hosts for a variety of chemical and biological applications.

The Detection of Food Additives Using a Fluorescence Indicator Based on 6- p-Toluidinylnaphthalence-2-sulfonate and Cationic Pillar[6]arene.

The current study investigated host-guest complexation in 6-p-toluidinylnaphthalene-2-sulfonate (TNS), a fluorescence probe used to investigate hydrophobic regions that contain the water-soluble cationic pillar[6]arene (CP6). After complexation with CP6, the fluorescence intensity of TNS was significantly increased. The decreases in the fluorescence intensity of the TNS•CP6 complex when phenolic food-additives are added have been used in indicator displacement assays to detect food additives in the water.

Reconfigurable Liquids Constructed by Pillar[6]arene-Based Nanoparticle Surfactants.

The interfacial jamming of nanoparticle surfactants offers the possibility of structuring liquids and fabricating all-liquid constructs with advanced functionality. However, less attention has been given to structured liquids with multiple responsiveness. Here, we show a novel, yet highly simplified nanoparticle surfactant model, pillar[6]arene (PA[6]) surfactant, by taking advantage of the host-guest interactions between a water-soluble PA[6] and an oil-soluble ligand, ferrocenium terminated polystyrene. PA[6] surfactants form rapidly at the oil-water interface, assemble into an elastic film with excellent mechanical strength, and when jammed, offer a "solid-like" assembly to lock-in highly nonequilibrium shapes of the liquids. The interfacial assembly/jamming and disassembly/unjamming of PA[6] surfactants can be controlled by chemical redox or competitive guest reagents, endowing the structured liquids with redox or guest-competitive responsiveness.