Precise Synthesis of Concentric Ring, Helicoid, and Ladder Metallo-Polymers with Chevron-Shaped Monomers.

Molecular geometry represents one of the most important structural features and governs physical properties and functions of materials. Nature creates a wide array of substances with distinct geometries but similar chemical composition with superior efficiency and precision. However, it remains a formidable challenge to construct abiological macromolecules with various geometries based on identical repeating units, owing to the lack of corresponding synthetic approaches for precisely manipulating the connectivity between monomers and feasible techniques for characterizing macromolecules at the single-molecule level. Herein, we design and synthesize a series of tetratopic monomers with chevron stripe shape which serve as the key precursors to produce four distinct types of metallo-macromolecules with well-defined geometries, viz., the concentric hexagon, helicoid polymer, ladder polymer, and cross-linked polymer, via platinum-acetylide couplings. Concentric hexagon, helicoid, and ladder metallo-polymers are directly visualized by transmission electron microscopy, atomic force microscopy, and ultra-high-vacuum low-temperature scanning tunneling microscopy at the single-molecule level. Finally, single-walled carbon nanotubes (SWCNTs) are selected as the guest to investigate the structure-property relationship based on such macromolecules, among which the helicoid metallo-polymer shows high efficiency in wrapping SWCNTs with geometry-dependent selectivity.

Non-equilibrium Nanoassemblies Constructed by Confined Coordination on a Polymer Chain.

Biological systems employ non-equilibrium self-assembly to create ordered nanoarchitectures with sophisticated functions. However, it is challenging to construct artificial non-equilibrium nanoassemblies due to lack of control over assembly dynamics and kinetics. Herein, we design a series of linear polymers with different side groups for further coordination-driven self-assembly based on shape-complementarity. Such a design introduces a main-chain confinement which effectively slows down the assembly process of side groups, thus allowing us to monitor the real-time evolution of lychee-like nanostructures. The function related to the non-equilibrium nature is further explored by performing photothermal conversion study. The ability to observe and capture non-equilibrium states in this supramolecular system will enhance our understanding of the thermodynamic and kinetic features as well as functions of living systems.

Acid-Activated Motion Switching of DB24C8 between Two Discrete Platinum(II) Metallacycles.

The precise operation of molecular motion for constructing complicated mechanically interlocked molecules has received considerable attention and is still an energetic field of supramolecular chemistry. Herein, we reported the construction of two tris[2]pseudorotaxanes metallacycles with acid-base controllable molecular motion through self-sorting strategy and host-guest interaction. Firstly, two hexagonal Pt(II) metallacycles M1 and M2 decorated with different host-guest recognition sites have been constructed via coordination-driven self-assembly strategy. The binding of metallacycles M1 and M2 with dibenzo-24-crown-8 (DB24C8) to form tris[2]pseudorotaxanes complexes TPRM1 and TPRM2 have been investigated. Furthermore, by taking advantage of the strong binding affinity between the protonated metallacycle M2 and DB24C8, the addition of trifluoroacetic acid (TFA) as a stimulus successfully induces an acid-activated motion switching of DB24C8 between the discrete metallacycles M1 and M2. This research not only affords a highly efficient way to construct stimuli-responsive smart supramolecular systems but also offers prospects for precisely control multicomponent cooperative motion.

Synthesis of Metallopolymers and Direct Visualization of the Single Polymer Chain.

During the past few decades, the study of the single polymer chain has attracted considerable attention with the goal of exploring the structure-property relationship of polymers. It still, however, remains challenging due to the variability and low atomic resolution of the amorphous single polymer chain. Here, we demonstrated a new strategy to visualize the single metallopolymer chain with a hexameric or trimeric supramolecule as a repeat unit, in which Ru(II) with strong coordination and Fe(II) with weak coordination were combined together in a stepwise manner. With the help of ultrahigh-vacuum, low-temperature scanning tunneling microscopy (UHV-LT-STM) and scanning tunneling spectroscopy (STS), we were able to directly visualize both Ru(II) and Fe(II), which act as staining reagents on the repeat units, thus providing detailed structural information for the single polymer chain. As such, the direct visualization of the single random polymer chain is realized to enhance the characterization of polymers at the single-molecule level.

Method of calculating porosity based on M44 element images of the Mueller matrix.

As a drug carrier, the porosity of porous electrospun fiber can greatly affect its drug loading ability and stability. In this work, a method to calculate the porosity of porous electrospun fiber with a polarization micrograph is described. Different porosities of porous electrospun fibers were measured by scanning electron microscope images and transmission Mueller matrix M44 element images, respectively. Mueller matrix M44 element images were obtained after polarization micrograph and normalization. The pore areas of M44 images were extracted by region growing, and the contour parts were obtained by performing morphological operation on pore areas. The porosity calculated by the polarization microscope image is in good consistency with that measured by the scanning electron microscope. Our results will promote practical application of electrospun porous fibers in the early stage of screening a large number of porous materials in the biomedicine field.

Emissive Metallacycle-Crosslinked Supramolecular Networks with Tunable Crosslinking Densities for Bacterial Imaging and Killing.

The chemical structures and topologies of the crosslinks in supramolecular networks play a crucial role in their properties and functions. Herein, the preparation of a type of poly(N-isopropylacrylamide) (PNIPAAM)-based supramolecular networks crosslinked by emissive hexagonal metallacycles is presented. The topological connections in these networks greatly affect their properties, as evidenced by their differences in absorption, emission, lower critical solution temperature, and modulus along with the variation of crosslinking densities. The integration of PNIPAAM and metallacycles in the networks benefits them improved bioavailability, making them serve as reagents for bacterial imaging and killing. This study provides a strategy to prepare cavity-crosslinked polymer networks for antibacterial applications.

Spontaneous Formation of a Cross-Linked Supramolecular Polymer Both in the Solid State and in Solution, Driven by Platinum(II) Metallacycle-Based Host-Guest Interactions.

The recent progress in platinum(II) coordination-driven supramolecular polymers has had a substantial effect on the design of functional soft materials. However, the prospect of realizing polymerization induced by platinum(II) metallacycle-based host-guest interactions has received little attention until recently. Here we report the realization of supramolecular polymerization driven by platinum(II) metallacycle-based host-guest interactions both in the solid state and in solution. On the basis of the disclosed polymerization mechanism, we present a new strategy for the preparation of platinum(II) metallacycle-based supramolecular polymers.

Self-Healing Heterometallic Supramolecular Polymers Constructed by Hierarchical Assembly of Triply Orthogonal Interactions with Tunable Photophysical Properties.

Here, we present a method for the building of new bicyclic heterometallic cross-linked supramolecular polymers by hierarchical unification of three types of orthogonal noncovalent interactions, including platinum(II)-pyridine coordination-driven self-assembly, zinc-terpyridine complex, and host-guest interactions. The platinum-pyridine coordination provides the primary driving force to form discrete rhomboidal metallacycles. The assembly does not interfere with the zinc-terpyridine complexes, which link the discrete metallacycles into linear supramolecular polymers, and the conjugation length is extended upon the formation of the zinc-terpyridine complexes, which red-shifts the absorption and emission spectra. Finally, host-guest interactions via bis-ammonium salt binding to the benzo-21-crown-7 (B21C7) groups on the platinum acceptors afford the cross-linked supramolecular polymers. By continuous increase of the concentration of the supramolecular polymer to a relatively high level, supramolecular polymer gel is obtained, which exhibits self-healing properties and reversible gel-sol transitions stimulated by various external stimuli, including temperature, K+, and cyclen. Moreover, the photophysical properties of the supramolecular polymers could be effectively tuned by varying the substituents of the precursor ligands.

Fluorescent Metallacage-Core Supramolecular Polymer Gel Formed by Orthogonal Metal Coordination and Host-Guest Interactions.

Herein, we report the preparation of a multifunctional metallacage-core supramolecular gel by orthogonal metal coordination and host-guest interactions. A tetragonal prismatic cage with four appended 21-crown-7 (21C7) moieties in its pillar parts was first prepared via the metal-coordination-driven self-assembly of cis-Pt(PEt3)2(OTf)2, tetraphenylethene (TPE)-based sodium benzoate ligands and linear dipyridyl ligands. Further addition of a bisammonium linker to the cage delivered a supramolecular polymer network via the host-guest interactions between the 21C7 moieties and ammonium salts, which formed a supramolecular gel at relatively higher concentrations. Due to the incorporation of a TPE derivative as the fluorophore, the gel shows emission properties. Multiple stimuli responsiveness and good self-healing properties were also observed because of the dynamic metal coordination and host-guest interactions used to stabilize the whole network structure. Moreover, the storage and loss moduli of the gel are 10-fold those of the gel without the metallacage cores, indicating that the rigid metallacage plays a significant role in enhancing the stiffness of the gel. The studies described herein not only enrich the functionalization of fluorescent metallacages via elegant ligand design but also provide a way to prepare stimuli-responsive and self-healing supramolecular gels as robust and smart materials.

Cross-linked supramolecular polymer gels constructed from discrete multi-pillar[5]arene metallacycles and their multiple stimuli-responsive behavior.

A new family of discrete hexakis-pillar[5]arene metallacycles with different sizes have been successfully prepared via coordination-driven self-assembly, which presented very few successful examples of preparation of discrete multiple pillar[n]arene derivatives. These newly designed hexakis-pillar[5]arene metallacycles were well characterized with one-dimensional (1-D) multinuclear NMR ((1)H and (31) P NMR), two-dimensional (2-D) (1)H-(1)H COSY and NOESY, ESI-TOF-MS, elemental analysis, and PM6 semiempirical molecular orbital methods. Furthermore, the host-guest complexation of such hexakis-pillar[5]arene hosts with a series of different neutral ditopic guests G1-6 were well investigated. Through host-guest interactions of hexakis-pillar[5]arene metallacycles H2 or H3 with the neutral dinitrile guest G5, the cross-linked supramolecular polymers H2⊃(G5)3 or H3⊃(G5)3 were successfully constructed at the high-concentration region, respectively. Interestingly, these cross-linked supramolecular polymers transformed into the stable supramolecular gels upon increasing the concentrations to a relatively high level. More importantly, by taking advantage of the dynamic nature of metal-ligand bonds and host-guest interactions, the reversible multiple stimuli-responsive gel-sol phase transitions of such polymer gels were successfully realized under different stimuli, such as temperature, halide, and competitive guest, etc. The mechanism of such multiple stimuli-responsive processes was well illustrated by in situ multinuclear NMR investigation. This research not only provides a highly efficient approach to the preparation of discrete multiple pillar[n]arene derivatives but also presents a new family of multiple stimuli-responsive "smart" soft matters.

Lignin-cellulose complexes derived from agricultural wastes for combined antibacterial and tissue engineering scaffolds for cutaneous leishmaniasis wounds.

Bacterial infections in wounds significantly impair the healing process. The use of natural antibacterial products over synthetic antibiotics has emerged as a new trend to address antimicrobial resistance. An ideal tissue engineering scaffold to treat infected wounds should possess antibacterial properties, while simultaneously promoting tissue regrowth. Synthesis of hydrogel scaffolds with antibacterial properties using hemp shive (HT1/HT2) lignin, sugarcane bagasse (SCB) lignin and cellulose was carried out. All lignin samples had low molecular weights and were constituted of G-type ß-5 dimers, linked by ß-O-4 bonds, as determined by MALDI-TOF-MS. Hemp lignin was more cytotoxic to mouse fibroblasts (L929) compared to SCB lignin. All lignin samples demonstrated antibacterial properties against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis, with greater efficiency against Gram-negative strains. 3D hydrogels were engineered by crosslinking SCB lignin with SCB cellulose in varying weight ratios in the presence of epichlorohydrin. The stiffness of the hydrogels could be tailored by varying the lignin concentration. All hydrogels were biocompatible; however, better fibroblast adhesion was observed on the blended hydrogels compared to the 100% cellulose hydrogel, with the cellulose : lignin 70 : 30 hydrogel showing the highest L929 proliferation and best antibacterial properties with a 24-hour bacterial growth reduction ranging from 30.8 to 57.3%.

Long-term exposure to dietary emulsifier Tween 80 promotes liver lipid accumulation and induces different-grade inflammation in young and aged mice.

With the advent of industrialization, there has been a substantial increase in the production and consumption of ultra-processed foods (UPFs). These processed foods often contain artificially synthesized additives, such as emulsifiers. Emulsifiers constitute approximately half of the total amount of food additives, with Tween 80 being a commonly used emulsifier in the food industry. Concurrently, China is undergoing significant demographic changes, transitioning into an aging society. Despite this demographic shift, there is insufficient research on the health implications of food emulsifiers, particularly on the elderly population. In this study, we present novel findings indicating that even at low concentrations, Tween 80 suppressed the viability of multiple cell types. Prolonged in vivo exposure to 1 % Tween 80 in drinking water induced liver lipid accumulation and insulin resistance in young adult mice under a regular chow diet. Intriguingly, in mice with high-fat diet (HFD) induced metabolic dysfunction-associated steatotic liver disease (MASLD), this inductive effect was masked. In aged mice, liver lipid accumulation was replicated under prolonged Tween 80 exposure. We further revealed that Tween 80 induced inflammation in both adult and aged mice, with a more pronounced inflammation in aged mice. In conclusion, our study provides compelling evidence that Tween 80 could contribute to a low-grade inflammation and liver lipid accumulation. These findings underscore the need for increasing attention regarding the consumption of UPFs with Tween 80 as the emulsifier, particularly in the elderly consumers.

Ultra-pH-sensitive nanoparticle of gambogenic acid for tumor targeting therapy via anti-vascular strategy plus immunotherapy.

Although the combination of anti-vascular strategy plus immunotherapy has emerged as the optimal first-line treatment of hepatocellular carcinoma, lack of tumor targeting leads to low antitumor efficacy and serious side effect. Here, we report an ultra-pH-sensitive nanoparticle of gambogenic acid (GNA) encapsulated by poly(ethylene glycol)-poly(2-azepane ethyl methacrylate) (PEG-PAEMA) for tumor-targeting combined therapy of anti-vascular strategy plus immunotherapy. PEG-PAEMA-GNA nanoparticle was quite stable at pH 7.4 for 30 d. In contrast, it exerted size shrinkage, charge reversal and the release of GNA at pH 6.7 within 24 h. Moreover, PEG-PAEMA-GNA significantly enhanced the anti-vascular activity, membrane-disruptive capability and pro-apoptosis when pH changed from 7.4 to 6.7. Western blot analysis exhibits that PEG-PAEMA and its GNA nanoparticle facilitated the phosphorylation of STING protein. In vivo assays show that PEG-PAEMA-GNA not only displayed much higher tumor inhibition of 92 % than 37 % of free GNA, but also inhibited tumor vasculature, promoted the maturation of dendritic cells and recruited more cytotoxic t-lymphocytes for sufficient anti-vascular therapy and immunotherapy. All these results demonstrate that PEG-PAEMA-GNA displayed tumor-targeting combined treatment of anti-vascular therapy and immunotherapy. This study offers a simple and novel method for the combination of anti-vascular therapy and immunotherapy with high selectivity towards tumor.

Systemically administered liposome-encapsulated Ad-PEDF potentiates the anti-cancer effects in mouse lung metastasis melanoma.

BACKGROUND: The use of adenoviral vector for gene therapy is still an important strategy for advanced cancers, however, the lack of the requisite coxsackie-adenovirus receptor in cancer cells and host immune response to adenovirus limit the application of adenoviral vector in vivo. METHOD: We designed the antiangiogenic gene therapy with recombinant PEDF adenovirus (Ad-PEDF) encapsulated in cationic liposome (Ad-PEDF/Liposome), and investigated the anti-tumor efficacy of Ad-PEDF/Liposome complex on inhibition of tumor metastasis. RESULTS: We found that systemic administration of Ad-PEDF/liposome was well tolerated and resulted in marked suppression of tumor growth, and was more potent than uncoated Ad-PEDF to induce apoptosis in B16-F10 melanoma cells and inhibit murine pulmonary metastases in vivo. After Ad-luciferase was encapsulated with liposome, its distribution decreased in liver and increased in lung. The anti-Ad IgG level of Ad-PEDF/Liposome was significantly lower than Ad-PEDF used alone. CONCLUSION: The present findings provide evidences of systematic administration of cationic liposome-encapsulated Ad-PEDF in pulmonary metastatic melanoma mice model, and show an encouraging therapeutic effect for further exploration and application of more complexes based on liposome-encapsulated adenovirus for more cancers.

Construction of metallo-helicoids with high antimicrobial activity via intermolecular coordination.

Metallo-helicoids are constructed by intermolecular coordination interactions between covalent linear polymer and tritopic/hexatopic molecular templates. These metallo-polymers with helicoidal conformation exhibit high antimicrobial activities against both Gram-positive and Gram-negative pathogens.

Digital micelles of encoded polymeric amphiphiles for direct sequence reading and ex vivo label-free quantification.

Identification and quantification of synthetic polymers in complex biological milieu are crucial for delivery, sensing and scaffolding functions, but conventional techniques based on imaging probe labellings only afford qualitative results. Here we report modular construction of precise sequence-defined amphiphilic polymers that self-assemble into digital micelles with contour lengths strictly regulated by oligourethane sequences. Direct sequence reading is accomplished with matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry, facilitated by high-affinity binding of alkali metal ions with poly(ethylene glycol) dendrons and selective cleavage of benzyl-carbamate linkages. A mixture of four types of digital micelles could be identified, sequence-decoded and quantified by MALDI and MALDI imaging at cellular, organ and tissue slice levels upon in vivo administration, enabling direct comparison of biological properties for each type of digital micelle in the same animal. The concept of digital micelles and encoded amphiphiles capable of direct sequencing and high-throughput label-free quantification could be exploited for next-generation precision nanomedicine designs (such as digital lipids) and protein corona studies.

Nanopatterned Electroactive Polylactic Acid Nanofibrous MOFilters for Efficient PM0.3 Filtration and Bacterial Inhibition.

Biodegradable polylactic acid (PLA) nanofibrous membranes (NFMs) hold great potential to address the increasing airborne particulate matter (PM) and dramatic accumulation of plastic/microplastic pollution. However, the field of PLA NFM-based filters is still in its infancy, frequently dwarfed by the bottlenecks regarding relatively low surface activity, poor electroactivity, and insufficient PM capturing mechanisms. This effort discloses a microwave-assisted approach to minute-level synthesis of dielectric ZIF-8 nanocrystals with high specific surface area (over 1012 m2/g) and ultrasmall size (∼240 nm), which were intimately anchored onto PLA nanofibers (PLA@ZIF-8) by a combined "electrospinning-electrospray" strategy. This endowed the PLA@ZIF-8 NFMs with largely increased electroactivity in terms of elevated dielectric coefficient (an increase of 202%), surface potential (up to 5.8 kV), and triboelectric properties (output voltage of 30.8 V at 10 N, 0.5 Hz). Given the profound control over morphology and electroactivity, the PLA@ZIF-8 NFMs exhibited efficient filtration of PM0.3 (97.1%, 85 L/min) with a decreased air resistance (592.5 Pa), surpassing that of the pure PLA counterpart (88.4%, 650.9 Pa). This was essentially ascribed to realization of multiple filtration mechanisms for PLA@ZIF-8 NFMs, including enhanced physical interception, polar interactions, and electrostatic adsorption, and the unique self-charging function triggered by airflow vibrations. Moreover, perfect antibacterial performance was achieved for PLA@ZIF-8, showing ultrahigh inhibition rates of 99.9 and 100% against E. coli and S. aureus, respectively. The proposed hierarchical structuring strategy, offering the multifunction integration unattainable with conventional methods, may facilitate the development of biodegradable long-term air filters.

Porous Polymers as Universal Reversal Agents for Heparin Anticoagulants through an Inclusion-Sequestration Mechanism.

Heparins are widely used anticoagulants for surgical procedures and extracorporeal therapies. However, all of them have bleeding risks. Protamine sulfate, the only clinically approved antidote for unfractionated heparin (UFH), has adverse effects. Moreover, protamine can only partially neutralize low-molecular-weight heparins (LMWHs) and is not effective for fondaparinux. Here, an inclusion-sequestration strategy for efficient neutralization of heparin anticoagulants by cationic porous supramolecular organic frameworks (SOFs) and porous organic polymers (POPs) is reported. Isothermal titration calorimetric and fluorescence experiments show strong binding affinities of these porous polymers toward heparins, whereas dynamic light scattering and zeta potential analysis confirm that the heparin sequences are adsorbed into the interior of the porous hosts. Activated partial thromboplastin time, anti-FXa, and thromboelastography assays indicate that their neutralization efficacies are higher than or as high as that of protamine for UFH and generally superior to protamine for LMWHs and fondaparinux, which is further confirmed by tail-transection model in mice and ex vivo aPTT or anti-FXa analysis in rats. Acute toxicity evaluations reveal that one of the SOFs displays outstanding biocompatibility. This work suggests that porous polymers can supply safe and rapid reversal of clinically used heparins, as protamine surrogates, providing an improved approach for their neutralization.

Antifouling poly(ß-peptoid)s.

A new type of polymer highly resistant to nonspecific protein adsorption is reported. Poly(N-methyl-ß-alanine) (PMeA) and poly(N-ethyl-ß-alanine) (PEtA) synthesized via cobalt-catalyzed carbonylative polymerization of N-methylaziridine and N-ethylaziridine were end-functionalized with thiol groups and grafted onto Au surfaces. Protein adsorption was studied by the surface plasmon resonance (SPR) method. The amounts of representative single proteins adsorbed onto the PMeA- and PEtA-grafted surfaces were below the detection limit of SPR at the pg/mm(2) level. After exposure to full blood plasma and serum for 10 min, protein adsorption was at the level of ∼ 100 pg/mm(2), similar to the level of protein adsorption on poly(ethylene glycol) surfaces subjected to identical conditions. These poly(ß-peptoid)s therefore provide excellent protein resistance comparable to the best antifouling materials known to date. The strong proton-accepting ability when forming hydrogen bonds is suggested to be an important attribute for these poly(ß-peptoid)s as well as other poly(tertiary amide)s as antifouling materials.

Robust All-Cellulose Nanofiber Composite from Stack-Up Bacterial Cellulose Hydrogels via Self-Aggregation Forces.

All-cellulose composites are usually prepared by removing impurities and using a surface-selective dissolution approach, which detract significantly from their environment-friendly properties. In this paper, we report an environment-friendly approach to fabricate all-cellulose nanofiber composites from stack-up bacterial cellulose (BC) hydrogels via self-aggregation forces of the hydrogen bond by water-based processing. Structural and mechanical properties of BC-laminated composites have been investigated. The results indicated that BC composites possess the structure of all nanofibers, a tensile strength of 116 MPa, and a storage modulus of 25 GPa. Additionally, the interfacial shear strength and tensile strength of piece-hot-press BC demonstrate the strong self-aggregation forces of BC nanofibers. Thus, BC-laminated composites will be attractive in structural material.