Supramolecular Coordination Complexes for Synergistic Cancer Therapy.

Supramolecular coordination complexes (SCCs) are predictable and size-tunable supramolecular self-assemblies constructed through directional coordination bonds between readily available organic ligands and metallic receptors. Based on planar and 3D structures, SCCs can be mainly divided into two categories: metallacycles (e.g., rhomboidal, triangular, rectangular, and hexagonal) and metallacages (e.g., tetrahedral, hexahedral, and dodecahedral). The directional coordination bonds enable the efficient formation of metallacycles and metallacages with well-defined architectures and geometries. SCCs exhibit several advantages, including good directionality, strong interaction force, tunable modularity, and good solution processability, making them highly attractive for biomedical applications, especially in cellular imaging and cancer therapy. Compared with their molecular precursors, SCCs demonstrate enhanced cellular uptake and a strengthened tumor accumulation effect, owing to their inherently charged structures. These properties and the chemotherapeutic potential inherent to organic platinum complexes have promoted their widespread application in antitumor therapy. Furthermore, the defined structures of SCCs, achieved via the design modification of assembly elements and introduction of different functional groups, enable them to combat malignant tumors through multipronged treatment modalities. Because the development of cancer-treatment methodologies integrated in clinics has evolved from single-modality chemotherapy to synergistic multimodal therapy, the development of functional SCCs for synergistic cancer therapy is crucial. While some pioneering reviews have explored the bioapplications of SCCs, often categorized by a specific function or focusing on the specific metal or ligand types, a comprehensive exploration of their synergistic multifunctionality is a critical gap in the current literature.In this Account, we focus on platinum-based SCCs and their applications in cancer therapy. While other metals, such as Pd-, Rh-, Ru-, and Ir-based SCCs, have been explored for cancer therapy by Therrien and Casini et al., platinum-based SCCs have garnered significant interest, owing to their unique advantages in antitumor therapy. These platinum-based SCCs, which enhance antitumor efficacy, are considered prominent candidates for cancer therapies owing to their desirable properties, such as potent antitumor activity, exceptionally low systemic toxicity, active tumor-targeting ability, and enhanced cellular uptake. Furthermore, diverse diagnostic and therapeutic modalities (e.g., chemotherapy, photothermal therapy, and photodynamic therapy) can be integrated into a single platform based on platinum-based SCCs for cancer therapy. Consequently, herein, we summarize our recent research on platinum-based SCCs for synergistic cancer therapy with particular emphasis on the cooperative interplay between different therapeutic methods. In the Conclusions section, we present the key advancements achieved on the basis of our research findings and propose future directions that may significantly impact the field.

Strategies to address key challenges of metallacycle/metallacage-based supramolecular coordination complexes in biomedical applications.

Owing to their capacity for dynamically linking two or more functional molecules, supramolecular coordination complexes (SCCs), exemplified by two-dimensional (2D) metallacycles and three-dimensional (3D) metallacages, have gained increasing significance in biomedical applications. However, their inherent hydrophobicity and self-assembly driven by heavy metal ions present common challenges in their applications. These challenges can be overcome by enhancing the aqueous solubility and in vivo circulation stability of SCCs, alongside minimizing their side effects during treatment. Addressing these challenges is crucial for advancing the fundamental research of SCCs and their subsequent clinical translation. In this review, drawing on extensive contemporary research, we offer a thorough and systematic analysis of the strategies employed by SCCs to surmount these prevalent yet pivotal obstacles. Additionally, we explore further potential challenges and prospects for the broader application of SCCs in the biomedical field.

Multiple hydrogen bonding driven supramolecular architectures and their biomedical applications.

Supramolecular chemistry combines the strength of molecular assembly via various molecular interactions. Hydrogen bonding facilitated self-assembly with the advantages of directionality, specificity, reversibility, and strength is a promising approach for constructing advanced supramolecules. There are still some challenges in hydrogen bonding based supramolecular polymers, such as complexity originating from tautomerism of the molecular building modules, the assembly process, and structure versatility of building blocks. In this review, examples are selected to give insights into multiple hydrogen bonding driven emerging supramolecular architectures. We focus on chiral supramolecular assemblies, multiple hydrogen bonding modules as stimuli responsive sources, interpenetrating polymer networks, multiple hydrogen bonding assisted organic frameworks, supramolecular adhesives, energy dissipators, and quantitative analysis of nano-adhesion. The applications in biomedical materials are focused with detailed examples including drug design evolution for myotonic dystrophy, molecular assembly for advanced drug delivery, an indicator displacement strategy for DNA detection, tissue engineering, and self-assembly complexes as gene delivery vectors for gene transfection. In addition, insights into the current challenges and future perspectives of this field to propel the development of multiple hydrogen bonding facilitated supramolecular materials are proposed.

Biodegradable Lipid-Modified Poly(Guanidine Thioctic Acid)s: A Fortifier of Lipid Nanoparticles to Promote the Efficacy and Safety of mRNA Cancer Vaccines.

Lipid nanoparticles (LNPs)-based messenger RNA (mRNA) therapeutics have emerged with promising potentials in the fields of infectious diseases, cancer vaccines, and protein replacement therapies; however, their therapeutic efficacy and safety can still be promoted by the optimization of LNPs formulations. Unfortunately, current LNPs suffer from increased production of reactive oxygen species during translation, which leads to a decreased translation efficiency and the onset of inflammation and other side effects. Herein, we synthesize a lipid-modified poly(guanidine thioctic acid) polymer to fabricate novel LNPs for mRNA vaccines. The acquired G-LNPs significantly promote the translation efficiency of loaded mRNA and attenuate inflammation after vaccination through the elimination of reactive oxygen species that are responsible for translational inhibition and inflammatory responses. In vivo studies demonstrate the excellent antitumor efficacy of the G-LNPs@mRNA vaccine, and two-dose vaccination dramatically increases the population and infiltration of cytotoxic T cells due to the intense antitumor immune responses, thus generating superior antitumor outcomes compared with the mRNA vaccine prepared from traditional LNPs. By synergy with immune checkpoint blockade, the tumor inhibition of G-LNPs@mRNA is further boosted, indicating that G-LNPs-based mRNA vaccines will be powerful and versatile platforms to combat cancer.

Enhancing the Toughness and Strength of Polymers Using Mechanically Interlocked Hydrogen Bonds.

The energy dissipative features of hydrogen bonds under conditions of mechanical strain have provided an ongoing incentive to explore hydrogen bonding units for the purpose of controlling and customizing the mechanical properties of polymeric materials. However, there remains a need for hydrogen bond units that (1) possess directionality, (2) provide selectivity, (3) dissipate energy effectively, and (4) can be incorporated readily into polymeric materials to regulate their mechanical properties. Here, we report mechanically interlocked hydrogen bond units that incorporate multiple hydrogen bonds within a [2]catenane structure. The conformational flexibility and associated spatial folding characteristics of the [2]catenane units allow for molecular scale motion under external stress, while the interlocked structure serves as a pivot that maintains the directionality and selectivity of the resultant hydrogen bonding units. When incorporated into polymers, these interlocked hydrogen bond motifs serve to strengthen and toughen the resulting materials. This study not only presents a novel hydrogen bond unit for creating polymeric materials with improved mechanical properties but also underscores the unique opportunities that mechanically interlocked hydrogen bond structures may provide across a diverse range of applications.

Three-Dimensional Crystalline Organic Framework Stabilized by Molecular Mortise-and-Tenon Jointing.

Three-dimensional (3D) crystalline organic frameworks with complex topologies, high surface area, and low densities afford a variety of application prospects. However, the design and construction of these frameworks have been largely limited to systems containing polyhedron-shaped building blocks or those relying on component interpenetration. Here, we report the synthesis of a 3D crystalline organic framework based on molecular mortise-and-tenon jointing. This new material takes advantage of tetra(4-pyridylphenyl)ethylene and chlorinated bis(benzodioxaborole)benzene as building blocks and is driven by dative B-N bonds. A single-crystal X-ray diffraction analysis of the framework reveals the presence of two-dimensional (2D) layers with helical channels that are formed presumably during the boron-nitrogen coordination process. The protrusion of dichlorobenzene units from the upper and lower surfaces of the 2D layers facilitates the key mortise-and-tenon connections. These connections enable the interlocking of adjacent layers and the stabilization of an overall 3D framework. The resulting framework is endowed with high porosity and attractive mechanical properties, rendering it potentially suitable for the removal of impurities from acetylene.

Polymerization in living organisms.

Vital biomacromolecules, such as RNA, DNA, polysaccharides and proteins, are synthesized inside cells via the polymerization of small biomolecules to support and multiply life. The study of polymerization reactions in living organisms is an emerging field in which the high diversity and efficiency of chemistry as well as the flexibility and ingeniousness of physiological environment are incisively and vividly embodied. Efforts have been made to design and develop in situ intra/extracellular polymerization reactions. Many important research areas, including cell surface engineering, biocompatible polymerization, cell behavior regulation, living cell imaging, targeted bacteriostasis and precise tumor therapy, have witnessed the elegant demeanour of polymerization reactions in living organisms. In this review, recent advances in polymerization in living organisms are summarized and presented according to different polymerization methods. The inspiration from biomacromolecule synthesis in nature highlights the feasibility and uniqueness of triggering living polymerization for cell-based biological applications. A series of examples of polymerization reactions in living organisms are discussed, along with their designs, mechanisms of action, and corresponding applications. The current challenges and prospects in this lifeful field are also proposed.

How the Length of Through-Space Conjugation Influences the Clusteroluminescence of Oligo(Phenylene Methylene)s.

The length and mode of conjugation directly affect the molecular electronic structure, which has been extensively studied in through-bond conjugation (TBC) systems. Corresponding research greatly promotes the development of TBC-based luminophores. However, how the length and mode of through-space conjugation (TSC), one kind of weak interaction, influence the photophysical properties of non-conjugated luminophores remains a relatively unexplored field. Here, we unveil a non-linear relationship between TSC length and emission characteristics in non-conjugated systems, in contrast to the reported proportional correlation in TBC systems. More specifically, oligo(phenylene methylene)s (OPM[4]-OPM[7]) exhibit stronger TSC and prominent blue clusteroluminescence (CL) (≈440 nm) compared to shorter counterparts (OPM[2] and OPM[3]). OPM[6] demonstrates the highest solid-state quantum yield (40 %), emphasizing the importance of balancing flexibility and rigidity. Further theoretical calculations confirmed that CL of these oligo(phenylene methylene)s was determined by stable TSC derived from the inner rigid Diphenylmethane (DPM) segments within the oligomers instead of the outer ones. This discovery challenges previous assumptions and adds a new dimension to the understanding of TSC-based luminophores in non-conjugated systems.

Supramolecular Genome Editing: Targeted Delivery and Endogenous Activation of CRISPR/Cas9 by Dynamic Host-Guest Recognition.

We synthesize supramolecular poly(disulfide) (CPS) containing covalently attached cucurbit[7]uril (CB[7]), which is exploited not only as a carrier to deliver plasmid DNA encoding destabilized Cas9 (dsCas9), but also as a host to include trimethoprim (TMP) by CB[7] moieties through the supramolecular complexation to form TMP@CPS/dsCas9. Once the plasmid is transfected into tumor cells by CPS, the presence of polyamines can competitively trigger the decomplexation of TMP@CPS, thereby displacing and releasing TMP from CB[7] to stabilize dsCas9 that can target and edit the genomic locus of PLK1 to inhibit the growth of tumor cells. Following the systemic administration of TMP@CPS/dsCas9 decorated with hyaluronic acid (HA), tumor-specific editing of PLK1 is detected due to the elevated polyamines in tumor microenvironment, greatly minimizing off-target editing in healthy tissues and non-targeted organs. As the metabolism of polyamines is dysregulated in a wide range of disorders, this study offers a supramolecular approach to precisely control CRISPR/Cas9 functions under particular pathological contexts.

Adaptive and Robust Vitrimers Fabricated by Synergy of Traditional and Supramolecular Polymers.

Vitrimers offer a unique combination of mechanical performance, reprocessability, and recyclability that makes them highly promising for a wide range of applications. However, achieving dynamic behavior in vitrimeric materials at their intended usage temperatures, thus combining reprocessability with adaptivity through associative dynamic covalent bonds, represents an attractive but formidable objective. Herein, we couple boron-nitrogen (B-N) dative bonds and B-O covalent bonds to generate a new class of vitrimers, boron-nitrogen vitrimers (BNVs), to endow them with dynamic features at usage temperatures. Compared with boron-ester vitrimers (BEVs) without B-N dative bonds, the BNVs with B-N dative bonds showcase enhanced mechanical performance. The excellent mechanical properties come from the synergistic effect of the dative B-N supramolecular polymer and covalent boron-ester networks. Moreover, benefiting from the associative exchange of B-O dynamic covalent bonds above their topological freezing temperature (Tv), the resultant BNVs also possess the processability. This study leveraged the structural characteristics of a boron-based vitrimer to achieve material reinforcement and toughness enhancement, simultaneously providing novel design concepts for the construction of new vitrimeric materials.

Adaptisorption of Nonporous Polymer Crystals.

Although our knowledge and understanding of adsorptions in natural and artificial systems has increased dramatically during the past century, adsorption associated with nonporous polymers remains something of a mystery, hampering applications. Here we demonstrate a model system for adaptisorption of nonporous polymers, wherein dative B-N bonds and host-guest binding units act as the kinetic and thermodynamic components, respectively. The coupling of these two components enables nonporous polymer crystals to adsorb molecules from solution and undergo recrystallization as thermodynamically favored crystals. Adaptisorption of nonporous polymer crystals not only extends the types of adsorption in which the sorbate molecules are integrated in a precise and orderly manner in the sorbent systems, but also provides a facile and accurate approach to the construction of polymeric materials with precise architectures and integrated functions.

Industrial Separation Challenges: How Does Supramolecular Chemistry Help?

The chemical industry and the chemical processes underscoring it are under intense scrutiny as the demands for the transition to more sustainable and environmentally friendly practices are increasing. Traditional industrial separation systems, such as thermally driven distillation for hydrocarbon purification, are energy intensive. The development of more energy efficient separation technologies is thus emerging as a critical need, as is the creation of new materials that may permit a transition away from classic distillation-based separations. In this Perspective, we focus on porous organic cages and macrocycles that can adsorb guest molecules selectively through various host-guest interactions and permit molecular sieving behavior at the molecular level. Specifically, we summarize the recent advances where receptor-based adsorbent materials have been shown to be effective for industrially relevant hydrocarbon separations, highlighting the underlying host-guest interactions that impart selectivity and permit the observed separations. This approach to sustainable separations is currently in its infancy. Nevertheless, several receptor-based adsorbent materials with extrinsic/intrinsic voids or special functional groups have been reported in recent years that can selectively capture various targeted guest molecules. We believe that the understanding of the interactions that drive selectivity at a molecular level accruing from these initial systems will permit an ever-more-effective "bottom-up" design of tailored molecular sieves that, in due course, will allow adsorbent material-based approaches to separations to transition from the laboratory into an industrial setting.

Polymerization-Induced Crystallization of Dopant Molecules: An Efficient Strategy for Room-Temperature Phosphorescence of Hydrogels.

Conventional hydrogels such as polyacrylamide and polyacrylic acid ones seldom exhibit phosphorescences at ambient conditions, which limit their applications as optical materials. We propose and demonstrate here a facile strategy to afford these hydrogels with room-temperature phosphorescence by polymerization-induced crystallization of dopant molecules that results in segregation and confinement of the gel matrix with carbonyl groups and thus clusterization-induced phosphorescence. As a model system, crown ethers (CEs) are dissolved in an aqueous solution of concentrated acrylamide that greatly increases the solubility of CEs. During the polymerization process, CEs crystallize to form large spherulites in the polyacrylamide hydrogel. The crystallization arises from the drastically reduced solubility of CEs after the conversion of monomers to polymers during the gel synthesis. The resultant composite hydrogel with a water content of 67 wt % exhibits extraordinary phosphorescence behavior yet maintains good stretchability and resilience. We found that the partial gel matrix is squeezed and confined by in situ-formed crystals, leading to carbonyl clusters and thus phosphorescence emission. The composite gel shows green phosphorescence with an emission peak at 512 nm and a lifetime of 342 ms. The afterglow emission is detectable by the naked eye for several seconds. This strategy has good universality, as validated in other hydrogels with different polymeric matrices and dopant molecules. The development of hydrogels with good mechanical and phosphorescent properties should merit the design of multifunctional soft machines with applications in biomedical and engineering fields.

Nanoencapsulation-Induced Second Harmonic Generation in Pillararene-Based Host-Guest Complex Cocrystals.

The features of molecularly preferable centrosymmetric arrangements exclude organic nonlinear optical (NLO) materials for second harmonic generation (SHG) when used in the solid and crystalline states, which greatly limits their applications in optoelectronic devices. Herein, a pillar[5]arene (BrP5) is used as the macrocyclic host to encapsulate NLO molecules, 4-[4'-methoxystyryl]-1-methylpyridinium iodide (OM), 4-[2'-(5'-(dimethylamino)thiophen-2'-yl)vinyl]-1-methylpyridinium iodide (DAST), and 4-methoxy-ß-nitrostyrene (MNS), to alter the solid-state packing of these NLO molecules and manipulate their centrosymmetric arrangements. BrP5 forms 2:1 host-guest complexes with OM and DAST, while it forms a 1:1 host-guest complex with MNS. Experimental results show that the pillar[5]arene and each of these three NLO guests form a nanocapsule architecture along with an overall centrosymmetric crystal structure. However, the random orientation of OM and DAST molecules inside the 2:1 host-guest complex nanocapsules breaks the local centrosymmetric arrangement of the NLO molecules, resulting in strong SHG. On the contrary, for BrP5⊃MNS, the MNS molecules inside the pillar[5]arene cavities are unable to break the centrosymmetry. They have only one determined orientation in the one-dimensional (1D) channels of BrP5, while other MNS molecules in adjacent channels have the opposite direction. The centrosymmetry of the dipolar chains is strictly maintained with the cancellation of nonlinear polarization, resulting in the quenching of SHG. Furthermore, an ultrasound-induced host-guest crystallization method is developed for the fast preparation of these host-guest composite materials with NLO activity. This work opens a new way to construct solid-state organic NLO materials, which have potential in high-power lasers, optical switches, and imaging applications.

Pillararene-Based Variable Stoichiometry Co-Crystallization: A Versatile Approach to Diversified Solid-State Superstructures.

Variable stoichiometry co-crystals are important in solid-state supramolecular chemistry as they allow studies of structure-property relationships while permitting the synthesis of new scaffolds using identical synthons. In this work, we extend the concept of variable stoichiometry co-crystals into the realm of pillararene chemistry and show that this permits the rational construction of a diverse set of supramolecular structures in the solid state. Specifically, we report a series of variable stoichiometry co-crystals based on pillar[n]arenes and tetracyanobenzene (TCNB) and show that the combination of in-cavity complexation by pillar[n]arenes (n = 5,6) and outside binding with TCNB allows several types of co-crystals with different self-assembled superstructures to be isolated. The variable stoichiometry co-crystals of this study display different solid-state physicochemical properties, including colors and luminescence features. Among these pillar[n]arene-based co-crystals, we discovered unique crystallographic architectures wherein two sets of individual host-guest complexes co-exist in the solid state. These mixed co-crystal systems allow for vapochromic-based detection of n-bromoalkanes. This work highlights a new strategy for the construction of self-assembled superstructures in the solid state and for tuning their intrinsic characteristics, including their luminescent and substrate-responsive features.

Substrate-Responsive Pillar[5]arene-Based Organic Room-Temperature Phosphorescence.

Room-temperature phosphorescence (RTP) is a photophysical phenomenon typically associated with a long-lived emission that can be detected by the unaided eye. Several natural proteins display RTP, as do certain artificial polymers. In both cases, the RTP is ascribed to effective intramolecular through-space electronic communication. However, small molecules with internal electronic communication that enable RTP are relatively rare. Herein, we describe an alkyl halide-responsive RTP system consisting of a meta-formylphenyl-bearing pillar[5]arene derivative that supports effective through-space charge transfer (TSCT) within the pillararene cavity. Treatment with bromoethane, a heavy atom-containing guest for the pillar[5]arene host, serves to enhance the emission. An isomeric para-formylphenyl-bearing pillar[5]arene system proved ineffective in producing an RTP effect. Quantum chemical calculations based on single-crystal X-ray diffraction analyses provided insights into the structural determinants governing TSCT between the 1,4-dimethoxybenzene donor units and the formylphenyl groups of the pillar[5]arene, as well as the associated energy gaps and intersystem crossing channels. We believe that the present system and the associated mechanistic analysis provide the foundation for design of new small molecule with tunable RTP features.

Macrocycle-Based Solid-State Supramolecular Polymers.

Supramolecular polymers, generated by connecting monomers through noncovalent interactions, have received considerable attention over the past years, as they provide versatile platforms for developing diverse aesthetically pleasing polymeric structures with promising applications in a variety of fields, such as medicine, catalysis, and sensing. In the development of supramolecular polymers, macrocyclic hosts play a very important role. Benefiting from their abundant host-guest chemistry and self-assembly characteristics, macrocycles themselves or their host-guest complexes can self-assemble to form well-ordered supramolecular polymeric architectures including pseudopolyrotaxanes and polyrotaxanes. The integration of these topological structures into supramolecular polymeric materials also imbues them with some unforeseen functions. Current interest in macrocycle-based supramolecular polymers is mostly focused on the development of supramolecular soft materials in solution or gel-state, in which the dynamic nature of noncovalent interactions endows supramolecular polymers with a wealth of "smart" properties, such as multiresponsiveness and self-repair capabilities. While preparation of macrocycle-derived supramolecular polymers in the solid state is a relatively challenging but intriguing prospect, they are an important part of the field of supramolecular polymers. On one hand, the construction of macrocycle-based solid-state supramolecular polymers enables us to obtain new materials with novel properties and functions such as mechano-responsiveness. On the other hand, the molecular structures and arrangements in these materials are well-identified by X-ray crystallography techniques, offering a direct visual representation of the supramolecular polymerization process. The analysis of the role of noncovalent interactions in these architectures allows us to design more sophisticated and elegant supramolecular polymers in a highly rationalized and controllable manner. This Account serves to summarize the research progress on macrocycle-based solid-state supramolecular polymers (MSSPs), including the contributions toward this field made by our group. For constructing MSSPs, the key point is to control noncovalent interactions. Thus, in this Account, we primarily classify these MSSPs by different noncovalent interactions involved to connect the monomers, including metal-ligand interactions, host-guest interactions, π···π stacking, and halogen bonding. These noncovalent interactions are highly associated with the structures and functions of the resultant MSSPs. For instance, using metal-ligand interactions as driving forces, metal clusters can be introduced in MSSPs which afford systems with solid-state luminescence or proton conduction properties; supramolecular polymerization using macrocycle-based host-guest interactions can modulate the molecular arrangement of some specific molecules in the solid state, which further influences their solid-state properties; π···π stacking interactions and halogen bonding give chemists more choice to design MSSPs with various elements. The role of macrocyclic hosts in MSSPs is also revealed in these descriptions. Finally, the remaining challenges are identified for further development of future prospects. We hope that this Account can inspire new discoveries in the realm of supramolecular functional systems and offer new opportunities for the construction of supramolecular architectures and solid-state materials.

Self-Assembled Cage for In Situ Detecting Silver Cation in Water.

Here, a capsule-shaped cage comprising three monocationic arms was efficiently self-assembled by condensing a triscationic trisaldehyde and a trisamino linkage in water. Multivalence endows the cage with thermodynamic stability in water. Despite its triscationic nature, the cage is able to use its trisimino residue to coordinate a silver cation. As a comparison, other cations lead to cage decomposition or no coordination. The cage and Ag+-coordinated complex were both characterized and confirmed by NMR spectroscopy, mass spectrometry, and theoretical calculations. The metal-ligand complex exhibits a pale-yellow color that can be detectable by the naked eye. The Ag+-coordinated complex undergoes decoordination upon the addition of NaCl, during which the cage containing imine bonds remains intact. Such stability implies that the cage might be potentially employed in silver detection and mining.

Peptidomimetics based on ammonium decasubstituted pillar[5]arenes: Influence of the alpha-amino acid residue nature on cholinesterase inhibition.

Cholinesterase inhibitors are a group of medicines that are widely used for the treatment of cognitive impairments accompanying Alzheimer's disease as well as for the treatment of pathological muscle weaknesses syndromes such as myasthenia gravis. The search for novel non-toxic and effective cholinesterase inhibitors for creating neuroprotective and neurotransmitter agents is an urgent interdisciplinary problem. For the first time, the application of water-soluble pillar[5]arenes containing amino acid residues as effective cholinesterase inhibitors was shown. The influence of the nature of aliphatic and aromatic alpha-amino acid residues (glycine, l-alanine, l-phenylalanine and l-tryptophan) on self-assembly, aggregate's stability, cytotoxicity on A549 and LEK cells and cholinesterase inhibition was studied. It was found that the studied compounds with aliphatic amino acid residues showed a low inhibitory ability against cholinesterases. It was established that the pillar[5]arene containing fragments of l-phenylalanine is the most promising inhibitor of butyrylcholinesterase (IC50 = 0.32 ± 0.01 µM), the pillar[5]arene with l-tryptophan residues is the most promising inhibitor of acetylcholinesterase (IC50 = 0.32 ± 0.01 µM). This study has shown a possible application of peptidomimetics based on pillar[5]arenes to inhibit cholinesterase, as well as control the binding affinity to a particular enzyme in a structure-dependent manner.

Mechanically interlocked polymers based on rotaxanes.

The nature of mechanically interlocked molecules (MIMs) has continued to encourage researchers to design and construct a variety of high-performance materials. Introducing mechanically interlocked structures into polymers has led to novel polymeric materials, called mechanically interlocked polymers (MIPs). Rotaxane-based MIPs are an important class, where the mechanically interlocked characteristic retains a high degree of structural freedom and mobility of their components, such as the rotation and sliding motions of rotaxane units. Therefore, these MIP materials are known to possess a unique set of properties, including mechanical robustness, adaptability and responsiveness, which endow them with potential applications in many emerging fields, such as protective materials, intelligent actuators, and mechanisorption. In this review, we outline the synthetic strategies, structure-property relationships, and application explorations of various polyrotaxanes, including linear polyrotaxanes, polyrotaxane networks, and rotaxane dendrimers.