Advances in the synthesis and applications of macrocyclic polyamines.

Macrocyclic polyamines constitute a significant class of macrocyclic compounds that play a pivotal role in the realm of supramolecular chemistry. They find extensive applications across diverse domains including industrial and agricultural production, clinical diagnostics, environmental protection and other multidisciplinary fields. Macrocyclic polyamines possess a distinctive cavity structure with varying sizes, depths, electron-richness degrees and flexibilities. This unique feature enables them to form specific supramolecular structures through complexation with diverse objects, thereby attracting considerable attention from chemists, biologists and materials scientists alike. However, there is currently a lack of comprehensive summaries on the synthesis methods for macrocyclic polyamines. In this review article, we provide an in-depth introduction to the synthesis of macrocyclic polyamines while analysing their respective advantages and disadvantages. Furthermore, we also present an overview of the recent 5-year advancements in using macrocyclic polyamines as non-viral gene vectors, fluorescent probes, diagnostic and therapeutic reagents as well as catalysts. Looking ahead to future research directions on the synthesis and application of macrocyclic polyamines across various fields will hopefully inspire new ideas for their synthesis and use.

Advancing Flexible Sensors through On-Demand Regulation of Supramolecular Nanostructures.

The evolution of flexible sensors heavily relies on advances in soft-material design and sensing mechanisms. Supramolecular chemistry offers a powerful toolbox for manipulating nanoscale and molecular structures within soft materials, thus fostering recent advancements in flexible sensors and electronics. Supramolecular interactions have been utilized to nanoengineer functional sensing materials or construct chemical sensors with lower cost and broader targets. In this perspective, we will highlight the use of supramolecular interactions to regulate and optimize nanostructures within functional soft materials and illustrate their importance in expanding the nanocavities of bioreceptors for chemical sensing. Overall, a bridge between tissue-mimicking flexible sensors and cell-mimetic supramolecular chemistry has been built, which will further advance human healthcare innovation.

Easy Processable Photomechanical Thin Film Involving a Photochromic Diarylethene and a Thermoplastic Elastomer in Supramolecular Interaction.

A novel supramolecular photoactuator in the form of a thin film of centimetric size has been developed as an alternative to traditional liquid crystal elastomers (LCE) involving azobenzene (AZO) units or photochromic microcrystals. This thin film is produced through spin coating without the need for alignment or crosslinking. The photoactuator combines a photochromic dithienylethene (DTE) functionalized with ureidopyrimidinone (UPy) units, and a telechelic thermoplastic elastomer, also functionalized with UPy, allowing quadruple hydrogen bonding between the two components. Upon alternating ultraviolet (UV) and visible light exposure, the film exhibits reversible bending and color changes, studied using displacement and absorption tracking setups. For the first time, the photomechanical effect (PME) is quantitatively correlated with photochromism, showing that DTE units drive the movement under both UV (photocyclization) and visible (photoreversion) light. In situ illumination techniques reveal that the PME arises from photoinduced strain within 160 nm UPy-bonded DTE domains, which expand and contract by approximately 50% under UV and visible light, respectively. The semicrystalline nature of the elastomer and a robust supramolecular network connecting both components are critical in converting microscopic photostrain into macroscopic actuation.

Multivalent hydrogen-bonded architectures directed by self-complementarity between [Cu(2,2'-biimidazole)] and malonate building blocks.

The synthesis and structural characterization of four novel supramolecular hydrogen-bonded arrangements based on self-assembly from molecular `[Cu(2,2'-biimidazole)]' modules and malonate anions are presented, namely, tetrakis(2,2'-biimidazole)di-µ-chlorido-dimalonatotricopper(II) pentahydrate, [Cu3(C3H2O4)2Cl2(C6H6N4)4]·5H2O or [Cu(H2biim)2(µ-Cl)Cu0.5(mal)]2·5H2O, aqua(2,2'-biimidazole)malonatocopper(II) dihydrate, [Cu(C3H2O4)(C6H6N4)(H2O)]·2H2O or [Cu(H2biim)(mal)(H2O)]·2H2O, bis[aquabis(2,2'-biimidazole)copper(II)] dimalonatodiperchloratocopper(II) 2.2-hydrate, [Cu(C6H6N4)2(H2O)]2[Cu(C3H2O4)(ClO4)2]·2.2H2O or [Cu(H2biim)2(H2O)]2[Cu(mal)2(ClO4)2]·2.2H2O, and bis(2,2'-biimidazole)copper(II) bis[bis(2,2'-biimidazole)(2-carboxyacetato)malonatocopper(II)] tridecahydrate, [Cu(C6H6N4)2][Cu(C3H2O4)(C3H3O4)(C6H6N4)2]·13H2O or [Cu(H2biim)2][Cu(H2biim)2(Hmal)(mal)]2·13H2O. These assemblies are characterized by self-complementary donor-acceptor molecular interactions, demonstrating a recurrent and distinctive pattern of hydrogen-bonding preferences among the carboxylate, carboxylic acid and N-H groups of the coordinated 2,2'-biimidazole and malonate ligands. Additionally, coordination of the carboxylate group with the metallic centre helps sustain remarkable supramolecular assemblies, such as layers, helices, double helix columns or 3D channeled architectures, including mixed-metal complexes, into a single structure.

Harnessing Peptide-Based Hydrogels for Enhanced Cartilage Tissue Engineering.

Cartilage tissue engineering remains a formidable challenge due to its complex, avascular structure and limited regenerative capacity. Traditional approaches, such as microfracture, autografts, and stem cell delivery, often fail to restore functional tissue adequately. Recently, there has been a surge in the exploration of new materials that mimic the extracellular microenvironment necessary to guide tissue regeneration. This review investigates the potential of peptide-based hydrogels as an innovative solution for cartilage regeneration. These hydrogels, formed via supramolecular self-assembly, exhibit excellent properties, including biocompatibility, ECM mimicry, and controlled biodegradation, making them highly suitable for cartilage tissue engineering. This review explains the structure of cartilage and the principles of supramolecular and peptide hydrogels. It also delves into their specific properties relevant to cartilage regeneration. Additionally, this review presents recent examples and a comparative analysis of various peptide-based hydrogels used for cartilage regeneration. The review also addresses the translational challenges of these materials, highlighting regulatory hurdles and the complexities of clinical application. This comprehensive investigation provides valuable insights for biomedical researchers, tissue engineers, and clinical professionals aiming to enhance cartilage repair methodologies.

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).

Self-Assembled Hydrazide-Based Nanochannels: Efficient Water Translocation and Salt Rejection.

Nature has ingeniously developed specialized water transporters that effectively reject ions, including protons, while transporting water across membranes. These natural water channels, known as aquaporins (AQPs), have inspired the creation of Artificial Water Channels (AWCs). However, replicating superfast water transport with synthetic molecular structures that exclude salts and protons is a challenging task. This endeavor demands the coexistence of a suitable water-binding site and a selective filter for precise water transportation. Here, we present small-molecule hydrazides 1b-1d that self-assemble into a rosette-type nanochannel assembly through intermolecular hydrogen bonding and π-π stacking interactions, and selectively transport water molecules across lipid bilayer membranes. The experimental analysis demonstrates notable permeability rates for the 1c derivative, enabling approximately 3.18 × 108 water molecules to traverse the channel per second. This permeability rate is about one order of magnitude lower than that of AQPs. Of particular significance, the 1c ensures exclusive passage of water molecules while effectively blocking salts and protons. MD simulation studies confirmed the stability and water transport properties of the water channel assembly inside the bilayer membranes at ambient conditions.

Exploring the Impact of Ring Mobility on the Macroscopic Properties of Doubly Threaded Slide-Ring Gel Networks.

The integration of mechanically interlocked molecules (MIMs) into polymeric materials has led to the development of mechanically interlocked polymers (MIPs). One class of MIPs that have gained attention are slide-ring gels (SRGs), which are generally accessed by crosslinking rings on a main-chain polyrotaxane. The mobility of the interlocked crosslinking moieties along the polymer backbone imparts enhanced properties onto these networks. An alternative synthetic approach to SRGs is to use a doubly threaded ring as the crosslinking moiety, yielding doubly threaded slide-ring gel networks (dt-SRGs). In this study, a photo-curable ligand-containing thread was used to assemble a series of metal-templated pseudo[3]rotaxane crosslinkers that allow access to MIPs that contain doubly threaded interlocked rings. The physicochemical and mechanical properties of these dt-SRGs with varying size of the ring crosslinking moieties were investigated and compared to an entangled gel (EG) prepared by polymerizing the metal complex of the photo-curable ligand-containing thread, and a corresponding covalent gel (CG). Relative to the EG and CG, the dt-SRGs exhibit enhanced swelling behavior, viscoelastic properties, and stress relaxation characteristics. In addition, the macroscopic properties of dt-SRGs could be altered by "locking" ring mobility in the structure through remetalation, highlighting the impact of the mobility of the crosslinks.

Strategies and Applications for Supramolecular Protein Self-assembly.

Supramolecular chemistry achieves higher-order molecular self-assembly through non-covalent interactions. Utilizing supramolecular methods to explore the polymorphism of proteins, the building blocks of life, from a "bottom-up" perspective is essential for constructing diverse and functional biomaterials. In recent years, significant progress has been achieved in the design strategies and functional applications of supramolecular protein self-assembly, becoming a focal point for researchers. This paper reviews classical supramolecular strategies driving protein self-assembly, including electrostatic interactions, metal coordination, hydrogen bonding, hydrophobic interactions, host-guest interactions, and other mechanisms. We discuss how these supramolecular interactions regulate protein assembly processes and highlight protein supramolecular assemblies' unique structural and functional advantages in constructing artificial photosynthetic systems, protein hydrogels, bio-delivery systems, and other functional materials. The enormous potential and significance of supramolecular protein materials are elucidated. Finally, the challenges in preparing and applying protein supramolecular assemblies are summarized, and future development directions are projected.

An Integrated Polysaccharide Hydrogel with Versatile Fluorescence Responses through Noncovalent Reformation of Gel Aggregation and for Bioimaging.

Functionalized hydrogels, with their unique and adaptable structures, have attracted significant attention in materials and biomaterials research. Fluorescent hydrogels are particularly noteworthy for their sensing capabilities and ability to mimic cellular matrices, facilitating cell infiltration and tracking of drug delivery. Structural elucidation of hydrogels is crucial for understanding their responses to stimuli such as the pH, temperature, and solvents. This study developed a fluorescent hydrogel by functionalizing chitosan with p-cresol-based quinazolinone aldehyde. Confocal microscopy revealed the hydrogel's intriguing fluorogenic properties. The hydrogel exhibited enhanced fluorescence and a tunable network morphology, influenced by the THF-water ratio. The study investigated the control of gel network reformation in different media and analyzed the fluorescence responses and structural changes of the sugar backbone and fluorophore. Proper selection of mixed solvents is essential for optimizing the hydrogel as a fluorescence probe for bioimaging. This hydrogel demonstrated greater swelling properties, making it highly suitable for drug delivery applications.

General and Modular Synthesis of Covalent Organic Cages for Efficient Molecular Recognition.

Cage-type structures based on coordination and dynamic covalent chemistry have the characteristics of facile and efficient preparation but poor stability. Chemically stable organic cages, generally involving fragment coupling and multi-step reactions, are relatively difficult to synthesize. Herein, we offer a general and modular strategy to customize covalent organic cages with diverse skeletons and sizes. First, one skeleton (S) module with three extension (E) modules and three reaction (R) modules are connected by one- or two-step coupling to get the triangular monomer bearing three reaction sites. Then one-pot Friedel-Crafts condensation of the monomer and linking module of paraformaldehyde produces the designed organic cages. The cage forming could be regulated by the geometrical configuration of monomeric blocks. The S-E-R angles in the monomer is crucial; only 120o (2,4-dimethoxyphen as reaction module) or 60o (2,5-dimethoxyphen as reaction module) angle between S-E-R successfully affords the resulting cages. By the rational design of the three modules, a series of organic cages have been constructed. In addition, the host-guest properties show that the representative cages could strongly encapsulate neutral aromatic diimine guests driven by solvophobic interactions in polar solvents, giving the highest association constant of (2.58 ± 0.18) × 105 M-1.

Synthesis of Adhesive Polyrotaxanes through Sequential Self-Assembly via Supramolecular Interactions and Dynamic Covalent Interactions.

Self-assembly is an effective approach to construct complicated structures. Polyrotaxanes (PRs) as one of the typical polymer types with complex structure, own interlocked structures and dynamic components, in which it results in unique characteristics and functions. Currently, the synthesis of which involves covalent reactions to hinder the development of polyrotaxanes. Herein, we employed supramolecular interactions as well as dynamic covalent bonds to synthesize PRs by sequential self-assembly. First, we prepared M1 possessing two diamine structures and M2 of a bisammonium salt with two dibenzylammonium (DBA) units modified by two stoppers at its ends, then M1 and M2 self-assembled into supramolecular polymers stemming from hydrogen bonding of [N+-H···O] under high concentrations. After adding 2,6-pyridinedicarboxaldehyde (M3), the imine bond formation enabled the generation of macrocycles, transforming supramolecular polymers into PRs. Besides, the solution of polyrotaxanes was applied as the adhesive for diverse hard and soft materials. This strategy provides an important approach for synthesizing PRs, accelerating the advances of mechanically interlocked polymers.

Super-Durable, Tough Shape-Memory Polymeric Materials Woven from Interlocking Rigid-Flexible Chains.

Developing advanced engineering polymers that combine high strength and toughness represents not only a necessary path to excellence but also a major technical challenge. Here for the first time a rigid-flexible interlocking polymer (RFIP) is reported featuring remarkable mechanical properties, consisting of flexible polyurethane (PU) and rigid polyimide (PI) chains cleverly woven together around the copper(I) ions center. By rationally weaving PI, PU chains, and copper(I) ions, RFIP exhibits ultra-high strength (twice that of unwoven polymers, 91.4 ± 3.3 MPa), toughness (448.0 ± 14.2 MJ m-3), fatigue resistance (recoverable after 10 000 cyclic stretches), and shape memory properties. Simulation results and characterization analysis together support the correlation between microstructure and macroscopic features, confirming the greater cohesive energy of the interwoven network and providing insights into strengthening toughening mechanisms. The essence of weaving on the atomic and molecular levels is fused to obtain brilliant and valuable mechanical properties, opening new perspectives in designing robust and stable polymers.

A bioinspired supramolecular nanoprodrug for precision therapy of B-cell non-Hodgkin's lymphoma.

Fludarabine (FA) is still considered as a first-line chemotherapy drug for hematological tumors related to B lymphocytes. However, it is worth noting that the non-specific distribution and non-different cytotoxicity of FA may lead to irreversible consequences such as central nervous system damage such as blindness, coma, and even death. Therefore, it is very important to develop a system to targeting delivery FA. In preliminary studies, it was found that B lymphoma cells would specific highly expressing the sialic acid-binding immunoglobulin-like lectin 2 (known as CD22). Inspired by the specific recognition of sialic acid residues and CD22, we have developed a supramolecular prodrug based on polysialic acid, an endogenous biomacromolecule, achieving targeted-therapy of B-cell non-Hodgkin's lymphoma (B-NHL). Specifically, the prepared hydrophobic reactive oxygen species-responsive FA dimeric prodrug (F2A) interacts with the TPSA, which polysialic acid were modified by the thymidine derivatives, through non-covalent intermolecular interactions similar to "Watson-Crick" base pairing, resulting in the formation of nanoscale supramolecular prodrug (F@TPSA). Cell experiments have confirmed that F@TPSA can be endocytosed by CD22+ B lymphoma cells including Raji and Ramos cells, and there is a significant difference of endocytosis in other leukocytes. Furthermore, in B-NHL mouse model, compared with FA, F@TPSA is determined to have a stronger tumor targeting and inhibitory effect. More importantly, the distribution of F@TPSA in vivo tends to be enriched in lymphoma tissue rather than nonspecific, thus reducing the leukopenia of FA. The targeted delivery system based on PSA provides a new prodrug modification strategy for targeted treatment of B-NHL.

Chirality and Curvature on Protein Adsorption and Osteogenesis.

Here we designed enantiomeric lipid-mimetic glutamic acid derivatives (L/D-UG) and investigated their self-assembled chiral nanostructures and performance with the protein adsorption as well as the osteogenesis. It was found that L or D-UG can self-assemble into vesicle bilayers and two-dimensional (2D) nanocrystals via a kinetic and thermodynamic control, respectively. These chiral vesicles and 2D crystals showed differentiated adsorption of proteins by their curvature and chirality. Specifically, fibronectin constituted by L-amino acids adsorbed preferentially on L-UG 2D crystal in a semi-random pattern and L-2D nanocrystal show as the most effective structures to promote bone regeneration. The controlled vesicle and 2D crystal assemblies with different chirality and curvature helps to clarify their determine roles in protein adsorption and osteogenesis.

Hexafluoroisopropanol-based supramolecular solvent for liquid phase microextraction of pesticides in milk.

Residues of pesticides in milk may pose a threat to human health. This study aimed to develop a liquid-phase microextraction (LPME) method using hexafluoroisopropanol (HFIP)-based supramolecular solvent (SUPRAS) for the simultaneous extraction and purification of four pesticides (boscalid, novaluron, cypermethrin and bifenthrin) in milk. Pesticides were extracted using SUPRAS prepared with nonanol and HFIP, and the extraction efficiency was analyzed. Results showed satisfactory recoveries ranging from 80.8%-111.0%, with relative standard deviations (RSDs) of <6.4%. Additionally, satisfactory linearities were observed, with correlation coefficients >0.9952. The limits of quantification (LOQs) were in the range of 1.8 µg·L-1-14.0 µg·L-1. The established method demonstrated high extraction efficiency with a short operation time (15 mins) and low solvent consumption (2.7 mL). The HFIP-based SUPRAS LPME method offers a convenient and efficient approach for the extraction of pesticides from milk, presenting a promising alternative to conventional techniques.

Heterochiral π-stacking dimerization of helical secondary structures with emerging supramolecular chirality.

In this work, we report a new type of interface modes between helical secondary structures by noncovalent assembly along the helical axis. The dimerization of helical secondary structures mediated by aromatic π-stacking leads to discrete heterochiral dimeric helical rods consisting of left-handed helix and right-handed helix, which has been demonstrated by single-crystal X-ray diffraction. We conduct chiral induction studies on discrete heterochiral dimers to regulate the preference of the helical sense. Surprisingly, we found a novel supramolecular chirality potentially occurring inside the super-secondary structure of chirality-induced heterochiral helical dimers, rather than the racemization of helical chirality. Furthermore, chirality-induced heterochiral helical dimers can exhibit unique chiral switches when formed or not formed. In order to identify the emerging supramolecular chirality of discrete heterochiral dimeric helix, we covalently synthesized meso-helix structures with opposite helical handedness. The chirality of aromatic chromophore linker was confirmed by chiral induction despite competition from opposite handed helices, which strongly demonstrates the occurrence of emerging supramolecular chirality in heterochiral dimeric helix. This study not only reports the heterochiral π-stacking dimerization of helical secondary structures for the first time, but also discovers novel supramolecular chirality hidden in the structure of noncovalent and even covalent meso-helices.

In vitro assessment of NaF/Chit supramolecular complex: colloidal stability, antibacterial activity and enamel protection against S. mutans biofilm.

OBJECTIVES: This study assessed the effect of NaF/Chit suspensions on enamel and on S. mutans biofilm, simulating application of a mouthrinse. METHODS: The NaF/Chit particle suspensions were prepared at molar ratio [NaF]/Chitmon]≈0.68 at nominal concentrations of 0.2% and 0.05% NaF and characterized by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering and zeta potential. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were measured. The S. mutans biofilm was formed for 7 days on eighty human enamel blocks that were divided into eight groups (n=10/group): i) 0.05% NaF solution; ii) 0.31% Chit solution; iii) NaF/Chit(R=0.68) suspension at 0.05% NaF; iv) 1.0% HAc solution (Control); v) 0.2% NaF solution; vi) 1.25% Chit solution; vii) NaF/Chit(R=0.68) suspension at 0.2% NaF; viii) 0.12% chlorhexidine digluconate. The substances were applied daily for 90s. S. mutans cell counts (CFU/mL) were performed, and the Knoop microhardness (KHN) of enamel samples were measured before and after biofilm formation. The KHN and CFU/mL data were analyzed by repeated measure ANOVA and Tukey's test (α = 0.05). RESULTS: Interactions between NaF and Chit were evidenced in solid state by FTIR spectra. The NaF/Chit complexes showed spontaneous microparticle formation and colloidal stability. The MIC and MBC ranged from 0.65-1.31 mg/mL. The NaF/Chit(R=0.68) suspension at 0.2%NaF Group showed lower CFU/mL values than other groups. The NaF/Chit(R=0.68) suspensions Groups had the highest KHN values after biofilm formation. CONCLUSIONS: The NaF/Chit(R=0.68) complexes exhibited an antibacterial effect against S. mutans biofilm and reduced the enamel hardness loss. CLINICAL SIGNIFICANCE: The NaF/Chit(R=0.68) suspensions showed potential to be used as a mouthrinse for caries prevention.

Chameleonic Cages: Encapsulation of Anionic, Neutral, and Cationic Guest Species within [Fe4L4]8+ Tetrahedral Cages Synthesised from the tris(4-aminophenyl)phosphate pro-Ligand.

An adaptable Fe(II) tetrahedral cage, [Fe4L4][BF4]8 (L = tris(4-(((E)-pyridin-2-ylmethylene)amino)phenyl) phosphate), has been synthesised via self-assembly. By modulating the orientation of its pendant P=O groups, the cage was found to be capable of encapsulating anionic, neutral, and cationic guests, which was confirmed in the solid state via single-crystal X-ray diffraction (SCXRD) and in solution by high-resolution mass spectroscopy (HR-MS), as well as by NMR (1H, 19F, 31P) studies where possible.

Ultra-Tough, yet Rigid and Healable Supramolecular Polymers with Variable Stiffness for Multimodal Actuators.

Variable stiffness materials have shown considerable application in soft robotics. However, previously reported materials often struggle to reconcile high stiffness, stretchability, toughness, and self-healing ability, because of the inherently conflicting requisite of these properties in molecular design. Herein, we propose a novel strategy that involves incorporating acid-base ionic pairs capable of from strong crosslinking sites into a dense and robust hydrogen-bonding network to construct rigid self-healing polymers with tunable stiffness and excellent toughness. To demonstrate these distinct features, the polymer was employed to serve as the strain-regulation layers within a fiber-reinforced pneumatic actuator (FPA). The exceptional synergy between the configuration versatility of FPA and the dynamic molecular behavior of the supramolecular polymers equips the actuator with simultaneous improvement in motion dexterity, multimodality, loading capacity, robustness, and durability. Additionally, the concept of integrating high dexterity at both macro- and micro-scale is prospective to inspire the design of intelligent yet robust devices across various domains.