An Antibiotic Nanobomb Constructed from pH-Responsive Chemical Bonds in Metal-Phenolic Network Nanoparticles for Biofilm Eradication and Corneal Ulcer Healing.

In the treatment of refractory corneal ulcers caused by Pseudomonas aeruginosa, antibacterial drugs delivery faces the drawbacks of low permeability and short ocular surface retention time. Hence, novel positively-charged modular nanoparticles (NPs) are developed to load tobramycin (TOB) through a one-step self-assembly method based on metal-phenolic network and Schiff base reaction using 3,4,5-trihydroxybenzaldehyde (THBA), ε-poly-ʟ-lysine (EPL), and Cu2+ as matrix components. In vitro antibacterial test demonstrates that THBA-Cu-TOB NPs exhibit efficient instantaneous sterilization owing to the rapid pH responsiveness to bacterial infections. Notably, only 2.6 µg mL-1 TOP is needed to eradicate P. aeruginosa biofilm in the nano-formed THBA-Cu-TOB owing to the greatly enhanced penetration, which is only 1.6% the concentration of free TOB (160 µg mL-1 ). In animal experiments, THBA-Cu-TOB NPs show significant advantages in ocular surface retention, corneal permeability, rapid sterilization, and inflammation elimination. Based on molecular biology analysis, the toll-like receptor 4 and nuclear factor kappa B signaling pathways are greatly downregulated as well as the reduction of inflammatory cytokines secretions. Such a simple and modular strategy in constructing nano-drug delivery platform offers a new idea for toxicity reduction, physiological barrier penetration, and intelligent drug delivery.

Pillararene-Based Stimuli-Responsive Supramolecular Delivery Systems for Cancer Therapy.

Cancer poses a significant challenge to global public health, seriously threatening human health and life. Although various therapeutic strategies, such as chemotherapy (CT), radiotherapy, phototherapy, and starvation therapy, are applied to cancer treatment, their limited therapeutic effect, severe side effects, and unsatisfactory drug release behavior need to be carefully considered. Thus, there is an urgent need to develop efficient drug delivery strategies for improving cancer treatment efficacy and realizing on-demand drug delivery. Notably, pillararenes, as an emerging class of supramolecular macrocycles, possess unique properties of highly tunable structures, superior host-guest chemistry, facile modification, and good biocompatibility, which are widely used in cancer therapy to achieve controllable drug release and reduce the toxic side effects on normal tissues under various internal/external stimuli conditions. This review summarizes the recent advance of stimuli-responsive supramolecular delivery systems (SDSs) based on pillararenes for tumor therapy from the perspectives of different assembly methods and hybrid materials, including molecular-scale SDSs, supramolecular nano self-assembly delivery systems, and nanohybrid SDSs. Moreover, the prospects and critical challenges of stimuli-responsive SDSs based on pillararenes for cancer therapy are also discussed.

Metal-Phenolic Nanocapsules with Photothermal Antibacterial and Ros Scavenging Ability for Diabetic Wound Healing.

The presence of bacteria in diabetic wounds not only leads to the formation of biofilms but also triggers oxidative stress and inflammatory responses, which hinder the wound-healing process. Therefore, it is imperative to formulate a comprehensive strategy that can proficiently eliminate bacteria and enhance the wound microenvironment. Herein, this work develops multifunctional metal-phenolic nanozymes (TA-Fe/Cu nanocapsules), wherein the one-pot coordination of tannic acid (TA)and Fe3+/Cu2+ using a self-sacrificial template afforded hollow nanoparticles (NPs) with exceptional photothermal and reactive oxygen species scavenging capabilities. After photothermal disruption of the biofilms, TA-Fe/Cu NPs autonomously capture bacteria through hydrogen bonding interactions with peptidoglycans (the bacterial cell wall component), ultimately bolstering the bactericidal efficacy. Furthermore, these NPs exhibit peroxidase-like enzymatic activity, efficiently eliminating surplus hydrogen peroxide in the vicinity of the wound and mitigating inflammatory responses. As the wound transitions into the remodeling phase, the presence of Cu2+ stimulates vascular migration and regeneration, expediting the wound-healing process. This study innovatively devises a minimalist approach to synthesize multifunctional metal-phenolic nanozymes integrating potent photothermal antibacterial activity, bacterial capture, anti-inflammatory, and angiogenesis properties, showcasing their great potential for diabetic wound treatment.

Pillararene-Based Supramolecular Polymers for Adsorption and Separation.

Supramolecular polymers have attracted increasing attention in recent years due to their perfect combination of supramolecular chemistry and traditional polymer chemistry. The design and synthesis of macrocycles have driven the rapid development of supramolecular chemistry and polymer science. Pillar[n]arenes, a new generation of macrocyclic compounds possessing unique pillar-shaped structures, nano-sized cavities, multi-functionalized groups, and excellent host-guest complexation abilities, are promising candidates to construct supramolecular polymer materials with enhanced properties and functionalities. This review summarizes recent progress in the design and synthesis of pillararene-based supramolecular polymers (PSPs) and illustrates their diverse applications as adsorption and separation materials. All performances are evaluated and analyzed in terms of efficiency, selectivity, and recyclability. Typically, PSPs can be categorized into three typical types according to their topologies, including linear, cross-linked, and hybrid structures. The advances made in the area of functional supramolecular polymeric adsorbents formed by new pillararene derivatives are also described in detail. Finally, the remaining challenges and future perspectives of PSPs for separation-based materials science are discussed. This review will inspire researchers in different fields and stimulate creative designs of supramolecular polymeric materials based on pillararenes and other macrocycles for effective adsorption and separation of a variety of targets.

Multimodal Therapeutic Platforms Based on Self-Assembled Metallacycles/Metallacages for Cancer Radiochemotherapy.

Discrete organometallic complexes with defined structures are proceeding rapidly in combating malignant tumors due to their multipronged treatment modalities. Many innovative superiorities, such as high antitumor activity, extremely low systemic toxicity, active targeting ability, and enhanced cellular uptake, make them more competent for clinical applications than individual precursors. In particular, coordination-induced regulation of luminescence and photophysical properties of organic light-emitting ligands has demonstrated significant potential in the timely evaluation of therapeutic efficacy by bioimaging and enabled synergistic photodynamic therapy (PDT) or photothermal therapy (PTT). This review highlights instructive examples of multimodal radiochemotherapy platforms for cancer ablation based on self-assembled metallacycles/metallacages, which would be classified by functions in a progressive manner. Finally, the essential demands and some plausible prospects in this field for cancer therapy are also presented.

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.

Smart organic materials based on macrocycle hosts.

Innovative design of smart organic materials is of great importance for the advancement of modern technology. Macrocycle hosts, possessing cyclic skeletons, intrinsic cavities, and specific guest binding properties, have demonstrated pronounced potential for the elaborate fabrication of a variety of functional organic materials with smart stimuli-responsive characteristics. In this tutorial review, we outline the current development of smart organic materials based on macrocycle hosts as key building blocks, focusing on the design principles and functional mechanisms of the tailored systems. Three main types of macrocycle-based smart organic materials are exemplified as follows according to the distinct forms of construction patterns: (1) supramolecular polymeric materials and nanoassemblies; (2) adaptive molecular crystals; (3) smart porous organic materials. The responsive performances of macrocycle-containing smart materials in versatile aspects, including mechanically adaptive polymers, soft optoelectronic devices, data encryption, drug delivery systems, artificial transmembrane channels, crystalline-state gas adsorption/separation, and fluorescence sensing, are illustrated by discussing the representative studies as paradigms, where the roles of macrocycles in these systems are highlighted. We also provide in the conclusion part the perspectives and remaining challenges in this burgeoning field.

Grinding-induced supramolecular charge-transfer assemblies with switchable vapochromism toward haloalkane isomers.

Synthetic macrocycles have proved to be of great application value in functional charge-transfer systems in the solid state in recent years. Here we show a switchable on-off type vapochromic system toward 1-/2-bromoalkane isomers by constructing solid-state charge-transfer complexes between electron-rich perethylated pillar[5]arene and electron-deficient aromatic acceptors including 4-nitrobenzonitrile and 1,4-dinitrobenzene. These charge-transfer complexes with different colors show opposite color changes upon exposure to the vapors of 1-bromoalkanes (fading) and 2-bromoalkanes (deepening). Single-crystal structures incorporating X-ray powder diffraction and spectral analyses demonstrate that this on-off type vapochromic behavior is mainly attributed to the destruction (off) and reconstruction (on) of the charge-transfer interactions between perethylated pillar[5]arene and the acceptors, for which the competitive host-guest binding of 1-bromoalkanes and the solid-state structural transformation triggered by 2-bromoalkanes are respectively responsible. This work provides a simple colorimetric method for distinguishing positional isomers with similar physical and chemical properties.

IrMo Nanocluster-Doped Porous Carbon Electrocatalysts Derived from Cucurbit[6]uril Boost Efficient Alkaline Hydrogen Evolution.

Electrocatalysts based on noble metals have been proven efficient for high-purity hydrogen production. However, the sluggish kinetics of the hydrogen evolution reaction (HER) in alkaline media caused by high water dissociation energy largely hampers this electrochemical process. To improve the electrocatalytic activity, we fabricate an effective porous carbon matrix derived from cucurbit[6]uril using a template-free method to support iridium-molybdenum (IrMo) nanoclusters. As proof of concept, the resulting IrMo-doped carbon electrocatalyst (IrMo-CBC) was found to boost the alkaline HER significantly. Owing to the unique in-plane hole structure and the nitrogen-rich backbone of cucurbit[6]uril as well as the ultrafine IrMo nanoclusters, IrMo-CBC exhibits pronounced alkaline HER activity with an extremely low overpotential of 12 mV at 10 mA cm-2, an ultrasmall Tafel slope (28.06 mV dec-1), a superior faradic efficiency (98%), and a TOF of 11.6 H2 s-1 at an overpotential of 50 mV, outperforming most iridium-based electrocatalysts and commercial Pt/C.

The Creation of DNA Origami-Based Supramolecular Nanostructures for Cancer Therapy.

DNA origami technology, a unique type of DNA nanotechnology, has attracted much attention from researchers and is applied in various fields. Through exquisite design and precise self-assembly of four kinds of deoxyribonucleotides, DNA origami nanostructures are endowed with excellent programmability and addressability and show outstanding biocompatibility in bio-related applications, especially in cancer treatment. In this review, nanomaterials based on DNA origami for cancer therapy are concluded, whereby chemotherapy and photo-assisted therapy are the main focus. Furthermore, the working mechanisms of the functional materials attached to the rigid DNA structures to enable targeted delivery and circumvent drug resistance are also discussed. DNA origami nanostructures are valuable carriers for delivering multifunctional therapeutic agents and demonstrate great potential in cancer treatment both in vitro and in vivo. It is undoubted that DNA origami technology is a promising strategy for constructing versatile nanodevices in biological fields and will excel in human healthcare.

Multifunctional Metal-Organic Framework (MOF)-Based Nanoplatforms for Crop Protection and Growth Promotion.

Phytopathogen, pest, weed, and nutrient deficiency cause severe losses to global crop yields every year. As the core engine, agrochemicals drive the continuous development of modern agriculture to meet the demand for agricultural productivity and increase the environmental burden due to inefficient use. With new advances in nanotechnology, introducing nanomaterials into agriculture to realize agrochemical accurate and targeted delivery has brought new opportunities to support the sustainable development of green agriculture. Metal-Organic frameworks (MOFs), which weave metal ions/clusters and organic ligands into porous frameworks, have exhibited significant advantages in constructing biotic/abiotic stimuli-responsive nanoplatforms for controlled agrochemical delivery. This review emphasizes the recent developments of MOF-based nanoplatforms for crop protection, including phytopathogen, pest, and weed control, and crop growth promotion, including fertilizer/plant hormone delivery. Finally, forward-looking perspectives and challenges on MOF-based nanoplatforms for future applications in crop protection and growth promotion are also discussed.

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.

Macrocycle-Based Crystalline Supramolecular Assemblies Built with Intermolecular Charge-Transfer Interactions.

Synthetic macrocycles have served as principal tools for supramolecular chemistry, have greatly extended the scope of organic charge transfer (CT) complexes, and have proved to be of great practical value in the solid state during the past few years. In this Minireview, we summarize the research progress on the macrocycle-based crystalline supramolecular assemblies primarily driven by intermolecular CT interactions (a.k.a. macrocycle-based crystalline CT assemblies, MCCAs for short), which are classified by their donor-acceptor (D-A) constituent elements, including simplex macrocyclic hosts, heterogeneous macrocyclic hosts, and host-guest D-A pairs. Particular attention will be focused on their diverse functions and applications, as well as the underlying CT mechanisms from the perspective of crystal engineering. Finally, the remaining challenges and prospects are outlined.

Multifunctional metal-organic framework (MOF)-based nanoplatforms for cancer therapy: from single to combination therapy.

Cancer remains a severe threat to human health. To date, although various therapeutic methods, including radiotherapy (RT), chemotherapy, chemodynamic therapy (CDT), phototherapy, starvation therapy, and immunotherapy, have entered a new stage of rapid progress in cancer theranostics, their limited therapeutic effect and significant side effects need to be considered carefully. With the rapid development of nanotechnology, the marriage of nanomaterials and therapeutic methods provides the practical possibility to improve the deficiencies in cancer therapy. Notably, metal-organic frameworks (MOFs) composed of ions/clusters and bridging ligands through coordination bonds have been widely applied in cancer therapy to deal with the drawbacks of different therapeutic methods, such as severe side effects, low stability, and poor efficacy, owing to their controllable morphologies, tailorable diameters, diverse compositions, tunable porosities, high specific surface areas, facile functionalization, and good biocompatibility. This review summarizes the recent advanced developments and achievements of multifunctional MOF-based nanoplatforms for cancer therapy through single therapy methods, including RT, chemotherapy, CDT, phototherapy (photodynamic and photothermal therapy), starvation therapy and immunotherapy, and combination therapy methods. Moreover, the prospects and challenges of MOF-based nanoplatforms used in tumor therapy are also discussed.

Tunable Photochromism of Spirooxazine in the Solid State: A New Design Strategy Based on the Hypochromic Effect.

As an important organic photofunctional material, spirooxazine (SO) usually does not exhibit photochromism in the solid state since the intermolecular π-π stacking impedes photoisomerization. Developing photochromic SO in the solid state is crucial for practical applications but is still full of challenges. Here, a series of spirooxazine derivatives (SO1-SO4) with bulky aromatic substituents at the 4- and 7-positions of the skeleton, which provide them with a large volume with which to undergo solid-state photochromism under mild conditions, is designed and synthesized. All the compounds SO1-SO4 exhibit tunable solid photochromism without ground colors, excellent fatigue resistance, and high thermal stability. Notably, it takes only 15 s for SO4 to reach the saturation of absorption intensity, thought to represent the fastest solid-state photoresponse of spirooxazines. X-ray crystal structures of the intermediate compound SO0 and the products SO1-SO2 as well as computational studies suggest that the bulky aromatic groups can lead to a hypochromic effect, allowing for the photochromism of SO in the solid state. The ideal photochromic properties of these spirooxazines open a new avenue for their applications in UV printing, quick response code, and related fields.

Self-Assembled Corrole/Chitosan Photothermal Nanoparticles for Accelerating Infected Diabetic Wound Healing.

Microvascular dysfunction caused by hyperglycemia leads to slow healing of diabetic wounds and significantly increases the risk of bacterial infection. The misuse of antibiotics can also lead to bacterial resistance, making the management of diabetic wounds more challenging. Thus, developing new antibacterial agents or strategies to overcome antibiotic resistance is highly pursued. Herein, novel supramolecular photothermal nanoparticles (MCC/CS NPs), assembled from mono-carboxyl corrole (MCC) and chitosan via hydrogen bonding and π-π stacking, are developed and used for treating bacterial wound infection. The MCC molecules possess good photothermal performance and the chitosan with inherent bioactivity can exert moderate antibacterial effects. The aggregation of MCC in MCC/CS NPs induced by chitosan-templated self-assembly further quenches molecular fluorescence and realizes an extraordinary photothermal conversion efficiency of 66.4%. Moreover, the highly positively charged MCC/CS NPs can selectively target bacteria via electrostatic interactions. Under near-infrared laser irradiation, the MCC/CS NPs achieve potent photothermal and inherent antimicrobial synergistic effects against Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) in vitro. Furthermore, the bacteria-infected diabetic wound model confirms that the MCC/CS NPs can effectively kill drug-resistant bacteria, accelerate wound healing and angiogenesis, and show good biocompatibility, representing a novel and efficient photothermal antibacterial nanoplatform.

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-Inspired Macrocycles: From Extended Pillar[n]arenes to Geminiarenes.

chemistry since their establishment due to their innate functional features of molecular recognition and complexation. The rapid development of modern supramolecular chemistry has also significantly benefited from creating new macrocycles with distinctive geometries and properties. For instance, pillar[n]arenes (pillarenes), a relatively young generation of star macrocyclic hosts among the well-established ones (e.g., crown ethers, cyclodextrins, cucurbiturils, and calixarenes), promoted a phenomenal research hotspot all over the world in the past decade. Although the synthesis, host-guest properties, and various supramolecular functions of pillarenes have been intensively studied, many objective limitations and challenges still cannot be ignored. For example, high-level pillar[n]arenes (n > 7) usually do not possess applicable large-sized cavities due to structural folding and cannot be synthesized on a large scale because of the uncompetitive cyclization process. Furthermore, two functional groups must be covalently para-connected to each repeating phenylene unit, which severely limits their structural diversity and flexibility. In this context, we have developed a series of pillarene-inspired macrocycles (PIMs) using a versatile and modular synthetic strategy during the past few years, aiming to break through the synthetic limitations in traditional pillarenes and find new opportunities and challenges in supramolecular chemistry and beyond. Specifically, by grafting biphenyl units into the pillarene backbones, extended pillar[n]arenes with rigid and nanometer-sized cavities could be obtained with reasonable synthetic yields by selectively removing hydroxy/alkoxy substitutes on pillarene backbones, leaning pillar[6]arenes and leggero pillar[n]arenes with enhanced structural flexibility and cavity adaptability were obtained. By combining the two types of bridging modes in pillarenes and calixarenes, a smart macrocyclic receptor with two different but interconvertible conformational features, namely geminiarene, was discovered. Benefiting from the synthetic accessibility, facile functionalization, and superior host-guest properties in solution or the solid state, this new family of macrocycles has exhibited a broad range of applications, including but not limited to supramolecular assembly/gelation/polymers, pollutant detection and separation, porous organic polymers, crystalline/amorphous molecular materials, hybrid materials, and controlled drug delivery. Thus, in this Account, we summarize our research efforts on these PIMs. We first present an overview of their design and modular synthesis and a summary of their derivatization strategies. Thereafter, particular attention is paid to their structural features, supramolecular functions, and application exploration. Finally, the remaining challenges and perspectives are outlined for their future development. We hope that this Account and our works can stimulate further advances in synthetic macrocyclic chemistry and supramolecular functional systems, leading to practical applications in various research areas.

Modulating Supramolecular Charge-Transfer Interactions in the Solid State using Compressible Macrocyclic Hosts.

Modulating intermolecular charge-transfer (ICT) interactions between specific donor and acceptor species in host-guest systems is a big challenge and full of research value in supramolecular chemistry and materials science. In this work, a strategy to modulate the supramolecular ICT interactions in the solid state is developed by compressing the binding cavity of a macrocyclic host named perethylated leaning pillar[6]arene (p-EtLP6). The solid-state ICT affinities of p-EtLP6 toward multi-types of electron-deficient planar guests could be significantly enhanced by transforming the macrocyclic backbone from the original para-bridged mode into a hybrid para- and meta-bridged isomeric form (m-EtLP6). X-ray single-crystal structural analyses incorporating theoretical calculation demonstrate that the improved ICT affinities are mainly attributed to the superior host-guest size fit arising from the compressed binding cavity in m-EtLP6 as compared with p-EtLP6.

The Anesthetic Strategy for Patients with Mucopolysaccharidoses: A Retrospective Cohort Study.

Anesthesia for patients with mucopolysaccharidoses (MPS) is quite challenging due to vital systemic dysfunction following progressive accumulation of lysosomal glycosaminoglycans. Previous studies focused on perioperative difficult airway management under general anesthesia but rarely depicted the concern of choosing the size of the endotracheal tube (ETT) as well as neuraxial anesthesia. This study aimed to analyze the overall anesthetic management and related complications for a thorough anesthetic strategy. Within the study period from 2002 to 2021, each record of the anesthetic and perioperative quality assurance/improvement system for patients with a diagnosis of MPS at MacKay Memorial Hospital was retrospectively reviewed. A total of 51 individuals with 151 anesthesia for 163 interventions were cohort studied, and there were 136 general anesthesia and 15 neuraxial anesthesia. We found that the most common interventions for MPS patients were otolaryngological surgeries (49.6%). Additionally, a secured airway played a marked preference for the most general anesthesia (87.1%). The incidence of difficult intubation was 12.5%. In view of ETT size, a smaller than estimated size was used in MPS type II, III, IV, and VI patients and also in patients who received intubation with multiple attempts. However, a larger than estimated size of ETT was adopted whilst choosing cuffed ones. For neuraxial anesthesia, two failed spinal anesthesia procedures were converted to general anesthesia and 73 percent of the patients received perioperative sedation. In conclusion, through the individualized anesthetic strategy and build-up of an experienced team for airway management, high-quality anesthesia can be ensured in each patient.