Atom-Precise Ligated Copper and Copper-Rich Nanoclusters with Mixed-Valent Cu(I)/Cu(0) Character: Structure-Electron Count Relationships.

Copper homometallic and copper-rich heterometallic nanoclusters with some Cu(0) character are reviewed. Their structure and stability are discussed in terms of their number of "free" electrons. In many aspects, this structural chemistry differs from that of their silver or copper homologs. Whereas the two-electron species are by far the most numerous, only one eight-electron species is known, but more electron-rich nanoclusters have also been reported. Owing to the relatively recent development of this chemistry, it is likely that more electron-rich species will be reported in the future.

One Stone, Two Birds: A Peptide-Au(I) Infinite Coordination Supermolecule for the Confederate Physical and Biological Radiosensitization in Cancer Radiation Therapy.

Over half of cancer patients are subjected to radiotherapy, but owing to the deficient amount of reactive oxygen radicals (ROS) and DNA double-strand breaks (DSBs), a fair number of them suffer from radiotherapy resistance and the subsequent short-term survival opportunity. To overcome it, many successes have been achieved in radiosensitizer discovery using physical strategy and/or biological strategy, but significant challenges remain regarding developing clinically translational radiosensitizers. Herein, a peptide-Au(I) infinite coordination supermolecule termed PAICS is developed that combined both physical and biological radiosensitization and possessed pharmaceutical characteristics including adequate circulatory stability, controllable drug release, tumor-prioritized accumulation, and the favorable body eliminability. As expected, monovalent gold ion endowed this supermolecule with high X-ray absorption and the subsequent radiosensitization. Furthermore, a peptide targeting CRM1, is assembled into the supermolecule, which successfully activates p53 and apoptosis pathway, thereby further sensitizing radiotherapy. As a result, PAICS showed superior ability for radiotherapy sensitization in vivo and maintained a favorable safety profile. Thus, the PAICS reported here will offer a feasible solution to simultaneously overcome both the pharmaceutical obstacles of physical and biological radiosensitizers and will enable the development of a class of nanomedicines for tumor radiotherapy sensitization.

Systematic, spatial imaging of large multimolecular assemblies and the emerging principles of supramolecular order in biological systems.

Understanding biological systems at the level of their relational (emergent) molecular properties in functional protein networks relies on imaging methods, able to spatially resolve a tissue or a cell as a giant, non-random, topologically defined collection of interacting supermolecules executing myriads of subcellular mechanisms. Here, the development and findings of parameter-unlimited functional super-resolution microscopy are described-a technology based on the fluorescence imaging cycler (IC) principle capable of co-mapping thousands of distinct biomolecular assemblies at high spatial resolution and differentiation (<40 nm distances). It is shown that the subcellular and transcellular features of such supermolecules can be described at the compositional and constitutional levels; that the spatial connection, relational stoichiometry, and topology of supermolecules generate hitherto unrecognized functional self-segmentation of biological tissues; that hierarchical features, common to thousands of simultaneously imaged supermolecules, can be identified; and how the resulting supramolecular order relates to spatial coding of cellular functionalities in biological systems. A large body of observations with IC molecular systems microscopy collected over 20 years have disclosed principles governed by a law of supramolecular segregation of cellular functionalities. This pervades phenomena, such as exceptional orderliness, functional selectivity, combinatorial and spatial periodicity, and hierarchical organization of large molecular systems, across all species investigated so far. This insight is based on the high degree of specificity, selectivity, and sensitivity of molecular recognition processes for fluorescence imaging beyond the spectral resolution limit, using probe libraries controlled by ICs.

Decoction regulating phytochemicals' micromorphology changes and anti-inflammation activity enhancements originated from herb medicine supermolecules.

BACKGROUND: Mahuang Fuzi decoction (MGF) is composed of three herb medicines that has been clinically used to treat inflammatory diseases for a long history. At present, more and more active phytochemicals' aggregations have been found during the thermodynamic process of herb medicine decoction, and revealing the clinical efficacy of herb medicine through supramolecular strategies is the focus of current research. However, it is not clear whether decoction induced supermolecules' morphological changes to modify activity. METHODS: Dynamic light scattering (DLS) and field emission scanning electron microscopy (FESEM) were used to analyze the micromorphology of MGF, MGF SA (MGF supermolecules), and MIX (physical mixture of MGF single decoction). The interaction and thermodynamic parameters of single herbs in a decoction were investigated by Isothermal titration calorimetry (ITC). The phytochemicals were systematically analyzed by ultra high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS). Under the safe dose on RAW264.7 cells, NO, IL-6 and TNF-α were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA) method. NF-κB p65 translocation from the cytoplasm into the nucleus was examined using the immunofluorescence assay and the western blot, respectively. Furthermore, Metabolomics was used to discover potential biomarkers and the associated metabolic pathways of MGF SA treatment. RESULTS: There were nanoscale aggregations in MGF, and the micromorphology of the extracted MGF SA consisted of uniform particles; while the MIX micromorphology had no uniformity. ITC showed that the interaction MH-GC and FZ-GC were a spontaneous exothermic reaction, indicating that their phytochemicals had the property of self-assembly. Though the micromorphology between MGF, MGF SA, and MIX was obviously different, UHPLC-Q-Orbitrap HRMS results displayed that the main phytochemicals of MGF and MIX had nearly the same components. Interestingly, MGF and MGF SA could significantly inhibit the production of NO, and had better inhibition effect on the expression of nuclear protein NF-κB p65 than MIX, among which MGF SA had the best effect. Further investigation indicated that the perturbance of metabolic profiling in RAW264.7 inflammatory cells was obviously reversed by MGF SA. CONCLUSIONS: The decoction enriched the key active phytochemicals and regulated the formation of homogeneous nanoparticles in MGF SA. The supermolecules in MGF SA significantly enhanced its anti-inflammatory activity, primarily affecting the NF-κB signaling pathway and the biosynthesis and metabolism of arginine in RAW264.7 inflammatory cells. Current study displayed that co-decocting herbal medicine were beneficial to the treatment of diseases than the mixture of the single herbs' extraction.

Aggregation-induced emission of 1,8-naphthalimide-casein micelle: investigation by synchronous spectrographic method.

A novel 1,8-naphthalimide probe 1, bearing two acetic-acid moieties was synthesized. The acetic-acid groups, docked into the sub-domains of casein micelle and bound with tryptophan residues, and the 1,8-naphthalimide chromophore adsorbed on the surface of casein micelle, forming a supermolecule, 1-casein micelle, which exhibited the aggregation-induced synchronous emission (AISE) characters. The effect of pH on the intensity of supermolecule was investigated, and the result indicated that the emission enhancement was mainly due to the 1,8-naphthalimide chromophore aggregated onto the casein micelle. Based on AISE, a novel casein quantification method was developed, which exhibited a good linear range of 0.05-10.0 µg ml(-1) and 0.07-9.5 µg ml(-1) with the detection limits of 2.8 and 3.0 ng ml(-1) . The effects of metal ions and pH on the system of 1-casein micelle were investigated. The proposed method was applied to determine casein in milk samples, and the results were in good agreement with the result of the Biuret method.

Insights into the Mechanism of Supramolecular Self-Assembly in the Astragalus membranaceus-Angelica sinensis Codecoction.

Astragalus membranaceus (Fisch.) Bge. (AM) and Angelica sinensis (Oliv.) Diels (AS) constitute a classic herb pair in prescriptions to treat myocardial fibrosis. To date, research on the AM-AS herb pair has mainly focused on the chemical compositions associated with therapeutic efficacy. However, supermolecules actually exist in herb codecoctions, and their self-assembly mechanism remains unclear. In this study, supermolecules originating from AM-AS codoping reactions (AA-NPs) were first reported. The chemical compositions of AA-NPs showed a dynamic self-assembly process. AA-NPs with different decoction times had similar surface groups and amorphous states; however, the size distributions of these nanoparticles might be different. Taking the interaction between Z-ligustilide and astragaloside IV as an example to understand the self-assembly mechanism of AA-NPs, it was found that the complex could be formed with a molar ratio of 2:1. Later, AA-NPs were proven to be effective in the treatment of myocardial fibrosis both in vivo and in vitro, the in-depth mechanisms of which were related to the recovery of cardiac function, reduced collagen deposition, and inhibition of the endothelial-to-mesenchymal transition that occurred in the process of myocardial fibrosis. Thus, AA-NPs may be the chemical material basis of the molecular mechanism of the AM-AS decoction in treating isoproterenol-induced myocardial fibrosis. Taken together, this work provides a supramolecular strategy for revealing the interaction between effective chemical components in herb-pair decoctions.

Dendroids, Discrete Covalently Cross-Linked Dendrimer Superstructures.

A versatile method is presented to form dendrimer superstructures by exploiting coacervate-core micelles as a template to confine and organize the hyperbranched macromolecules. First, complex coacervate-core micelles are formed from negative-neutral block copolymers and positively charged polyamidoamine dendrimers. The dendrimers inside the micellar core are then covalently cross-linked with each other upon addition of glutaraldehyde. After removal of the block copolymer from the assembly by increasing the salt concentration, consecutively, the formed Schiff bases cross-linking the dendrimers are reduced to amines, followed by a final dialysis step. This leads to well-defined covalently cross-linked nanostructures, coined dendroids, with a size of around 30 nm in diameter and a molecular weight of approximately 2.5 MDa. By incorporating dendrimer-encapsulated gold nanoparticles (AuDENs) into the micelle template strategy, the aggregation number of dendrimers inside the dendroids is determined by counting the nanoparticles in TEM micrographs. Furthermore, TEM performed at different tilt angles and AFM analysis corroborate formation of stable, covalently linked three-dimensional structures. Reconstruction of the TEM tilt series results in a tomogram further illustrating the 3D distribution of the gold nanoparticles, and hence the individual dendrimers, in the nanostructure. These dendroids appear to have a hard, poorly compressible core and a relatively soft outside. The versatility of the hierarchical building up of the supermolecules is illustrated by the controlled and synchronous incorporation of empty dendrimers and AuDENs into a single hybrid dendroid structure. The presented strategy allows for the preparation of a variety of classes of supermolecules, depending on the type of micellar-core macromolecule, e.g., dendrimer, cross-linker, and nanoparticles, used. Considering the broad interest in dendrimers as well as micelles in a plethora of research areas, e.g., (targeted) drug delivery, biomedical imaging, theragnostics, and catalysis, there is a great potential for dendroids and related classes of covalently linked macromolecules, viz., supermolecules.

Dielectric Relaxation and Beyond Limiting Behavior of Alternating-Current Conductivity in a Supermolecular Ferroelectric.

A cyclen-based hybrid supermolecule crystal, [(FeCl2 )(cyclen)]Cl (1), where cyclen=1,4,7,10-tetraazacyclododecane, was prepared using a liquid-liquid diffusion approach. The variable crystal structures exhibit that compound 1 belongs to an orthorhombic crystal system, Pna21 space group (point group C2V ) in the temperature range of 150-400 K. This hybrid supermolecule shows a dielectric relaxation behavior around room temperature, and the ferroelectric nature of 1 has been directly verified by hysteresis measurements. In addition, the AC (alternating current) conductivity study reveals that the 1 displays a beyond limiting behavior. These interesting findings are for the first time reported in the field of supermolecular ferroelectrics. This study may open a new way to construct supermolecular ferroelectrics and give insights into their conductor behavior.

Challenges and breakthroughs in recent research on self-assembly.

The controlled fabrication of nanometer-scale objects is without doubt one of the central issues in current science and technology. However, existing fabrication techniques suffer from several disadvantages including size-restrictions and a general paucity of applicable materials. Because of this, the development of alternative approaches based on supramolecular self-assembly processes is anticipated as a breakthrough methodology. This review article aims to comprehensively summarize the salient aspects of self-assembly through the introduction of the recent challenges and breakthroughs in three categories: (i) types of self-assembly in bulk media; (ii) types of components for self-assembly in bulk media; and (iii) self-assembly at interfaces.

Supermolecules of poly(N-isopropylacrylamide) complexating Herring sperm DNA with bio-multiple hydrogen bonding.

In this study we used the poly(N-isopropylacrylamide) (PNIPAAm) as a medium to blend with an organic DNA, herring sperm DNA (HSD), to generate PNIPAAm-HSD supramolecular complexes. Bio-multiple hydrogen bonding (BMHB) between PNIPAAm and HSD was investigated that changed the temperature responsiveness of PNIPAAm relatively to the HSD concentrations. With blending the HSD into PNIPAAm matrix, the phase separation in solution is completely opposite from that of neat PNIPAAm. Surface property in static water contact angle (SWCA) is also opposite from that of pure PNIPAAm upon increasing HSD content over 60%. In addition, we found that the PNIPAAm and HSD self-assembled a specific triangle-like structure at a PNIPAAm-to-HSD weight ratio of 1:4 at 25°C; while the triangle-like structure disappeared with increasing temperature to 45°C. Furthermore, both PNIPAAm and HSD could be regarded as insulator, but it transformed into a semiconductive matter after blending with the HSD. Incorporation of organic DNA with hydrogel could significantly change their properties, which might facilitate their use as novel materials in bioelectronics.