Liquid-Liquid Phase Separation Mediated Formation of Chiral 2D Crystalline Nanosheets of a Co-Assembled System.

The role of macromolecule-macromolecule and macromolecule-H2O interactions and the resulting perturbation of the H-bonded network of H2O in the liquid-liquid phase separation (LLPS) process of biopolymers are well-known. However, the potential of the hydrated state of supramolecular structures (non-covalent analogs of macromolecules) of synthetic molecules is not widely recognized for playing a similar role in the LLPS process. Herein, LLPS occurred during the co-assembly of hydrated supramolecular vesicles (bolaamphiphile, BA1) with a net positive charge (zeta potential, ζ = +60 ± 2 mV) and a dianionic chiral molecule (disodium l-[+]-tartrate) is reported. As inferred from cryo-transmission electron microscopy (TEM), the LLPS-formed droplets serve as the nucleation precursors, dictating the structure and properties of the co-assembly. The co-assembled structure formed by LLPS effectively integrates the counter anion's asymmetry, resulting in the formation of ultrathin free-standing, chiral 2D crystalline sheets. The significance of the hydrated state of supramolecular structures in influencing LLPS is unraveled through studies extended to a less hydrated supramolecular structure of a comparable system (BA2). The role of LLPS in modulating the hydrophobic interaction in water paves the way for the creation of advanced functional materials in an aqueous environment.

A Simple Binary Supramolecular Co-Assembly Platform for Enhanced Tumor Imaging and Therapy.

The primary challenges in tumor imaging and therapy revolve around improving targeting efficiency, enhancing probe/drug delivery efficacy, and minimizing off-target signals and toxicity. Although various carriers have been developed, many are difficult to synthesize, costly, and not universally applicable. Furthermore, numerous carriers exhibit limited delivery rates in solid tumors, particularly larger nanocarriers. To address these challenges, a simple binary co-assembly drug delivery platform has been designed using the readily synthesized small molecule Cys(SEt)-Lys-CBT (CKCBT) as the self-assembly building block. CKCBT can effectively penetrate tumor cells due to its positively charged Lys side chain and small size. Upon glutathione reduction, CKCBT co-assembles with Nile red or Chlorin e6 to form nanofibers inside tumor cells. This enables their specific accumulation in tumor cells rather than normal cells and extends their exposure time, resulting in precise and enhanced tumor imaging and treatment. Hence, this uncomplicated and highly efficient binary co-assembly drug delivery platform can be easily adapted to a broad spectrum of probes and drugs, presenting a novel approach for advancing clinical diagnosis and therapy.

Host-Guest Interaction Mediated Interfacial Co-Assembly of Cyclodextrin and Bottlebrush Surfactants for Precisely Tunable Photonic Supraballs.

Investigations of host-guest interactions at water-oil (w/o) interfaces are limited in single emulsion systems producing simple self-assembled objects with limited uses. Here, within hierarchically ordered water-in-oil-in-water (w/o/w) multiple emulsion droplets, interfacial self-assembly of (polynorbornene-graft-polystyrene)-block-(polynorbornene-graft-polyethylene glycol) (PNPS-b-PNPEG) bottlebrush block copolymers can be precisely controlled through host-guest interactions. α-Cyclodextrin (α-CD) in the aqueous phase can thread onto PEG side chains of the bottlebrush surfactants adsorbed at the w/o interface, leading to dehydration and collapsed chain conformation of the PEG block. Consequently, spherical curvature of the w/o internal droplets increases with the increased asymmetry of the bottlebrush molecules, producing photonic supraballs with precisely tailored structural parameters as well as photonic bandgaps. This work provides a simple but highly effective strategy for precise manipulation of complex emulsion systems applicable in a variety of applications, such as photonic pigments, cosmetic products, pesticides, artificial cells, etc.

Bisurea-Based Supramolecular Polymers for Tunable Biomaterials.

Water-soluble supramolecular polymers show great potential to develop dynamic biomaterials with tailored properties. Here, we elucidate the morphology, stability and dynamicity of supramolecular polymers derived from bisurea-based monomers. An accessible synthetic approach from 2,4-toluene diisocyanate (TDI) as the starting material is developed. TDI has two isocyanates that differ in intrinsic reactivity, which allows to obtain functional, desymmetrized monomers in a one-step procedure. We explore how the hydrophobic/hydrophilic ratio affects the properties of the formed supramolecular polymers by increasing the number of methylene units from 10 to 12 keeping the hydrophilic hexa(ethylene glycol) constant. All bisurea-based monomers form long, fibrous structures with 3-5 monomers in the cross-section in water, indicating a proper hydrophobic\hydrophilic balance. The stability of the supramolecular polymers increases with an increasing amount of methylene units, whereas the dynamic nature of the monomers decreases. The introduction of one Cy3 dye affords modified supramolecular monomers, which co-assemble with the unmodified monomers into fibrous structures. All systems show excellent water-compatibility and no toxicity for different cell-lines. Importantly, in cell culture media, the fibrous structures remain present, highlighting the stability of these supramolecular polymers in physiological conditions. The results obtained here motivate further investigation of these bisurea-based building blocks as dynamic biomaterial.

Strong Circularly Polarized Luminescence Promoted by AIE-active Chiral Co-assemblies in Liquid Crystal Polymer Films.

Recently, extensive works have focused on increasing the dissymmetry factors (glum) of various circularly polarized luminescence (CPL) materials, which is one of the most important factors for future applications of CPL. Herein, we designed a chiral co-assembled liquid crystal polymer (LCP) PTZ@R/S-PB2, which was prepared by chiral binary co-polymer (R/S-PB2) doped with achiral phenothiazine derivation dye (PTZ). For comparison, ternary co-polymerized LCP (R/S-PT) was synthesized by co-polymerizing with mesogenic monomer, chiral monomer and emissive monomer. Both PTZ@R/S-PB2 and R/S-PT showed aggregation-induced emission (AIE) properties. Interestingly, the CPL signals of both PTZ@R/S-PB2 and R/S-PT were reversed and amplified after thermal annealing treatment. The |glum| values of the co-assembled PTZ@R/S-PB2 were up to 0.13 at a 32 nm thickness, which was 5.4 times that of R/S-PT (|glum|=0.024). This is due to PTZ@R/S-PB2 could form more orderly chiral co-assembly structures. Noticeably, increasing the LCP film thickness could further improve the glum value, and the maximum glum of PTZ@R/S-PB2 could be enhanced to +0.91/-0.82 at a 220 nm thickness.

pH-sensitive release of nitric oxide gas using peptide-graphene co-assembled hybrid nanosheets.

Nitric oxide (NO) donating drugs such as organic nitrates have been used to treat cardiovascular diseases for more than a century. These donors primarily produce NO systemically. It is however sometimes desirable to control the amount, location, and time of NO delivery. We present the design of a novel pH-sensitive NO release system that is achieved by the synthesis of dipeptide diphenylalanine (FF) and graphene oxide (GO) co-assembled hybrid nanosheets (termed as FF@GO) through weak molecular interactions. These hybrid nanosheets were characterised by using X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, zeta potential measurements, X-ray photoelectron spectroscopy, scanning and transmission electron microscopies. The weak molecular interactions, which include electrostatic, hydrogen bonding and π-π stacking, are pH sensitive due to the presence of carboxylic acid and amine functionalities on GO and the dipeptide building blocks. Herein, we demonstrate that this formulation can be loaded with NO gas with the dipeptide acting as an arresting agent to inhibit NO burst release at neutral pH; however, at acidic pH it is capable of releasing NO at the rate of up to 0.6 µM per minute, comparable to the amount of NO produced by healthy endothelium. In conclusion, the innovative conjugation of dipeptide with graphene can store and release NO gas under physiologically relevant concentrations in a pH-responsive manner. pH responsive NO-releasing organic-inorganic nanohybrids may prove useful for the treatment of cardiovascular diseases and other pathologies.

Ring-opening polymerization of lactide catalyzed using metal-coordinated enzyme-like amino acid assemblies.

Polylactide (PLA), a biocompatible and biodegradable polymer, is widely used in diverse biomedical applications. However, the industry standard for converting lactide into PLA involves toxic tin (Sn)-based catalysts. To mitigate the use of these harmful catalysts, other environmentally benign metal-containing agents for efficient lactide polymerization have been studied, but these alternatives are hindered by complex synthesis processes, reactivity issues, and selectivity limitations. To overcome these shortcomings, we explored the catalytic activity of Cu-(Phe)2 and Zn-(Phe)2 metal-amino acid co-assemblies as potential catalysts of the ring-opening polymerization (ROP) of lactide into PLA. Catalytic activity of the assemblies was monitored at different temperatures and solvents using 1H-NMR spectroscopy to determine the catalytic parameters. Notably, Zn-(Phe)2 achieved >99% conversion of lactide to PLA within 12 h in toluene under reflux conditions and was found to have first-order kinetics, whereas Cu-(Phe)2 exhibited significantly lower catalytic activity. Following Zn-(Phe)2-mediated catalysis, the resulting PLA had an average molecular weight of 128 kDa and a dispersity index of 1.25 as determined by gel permeation chromatography. Taken together, our minimalistic approach expands the realm of metal-amino acid-based supramolecular catalytic nanomaterials useful in the ROP of lactide. This advancement shows promise for the future design of simplified biocatalysts in both industrial and biomedical applications.

Response of the algal-bacterial community to thermal stratification succession in a deep-water reservoir: Community structure, co-assembly patterns, and functional groups.

Thermal stratification in lakes and reservoirs may intensify and become more persistent with global warming. Periodic thermal stratification is a naturally occurring phenomenon that indicates a transition in aquatic ecosystem homeostasis, which could lead to the deterioration of water quality and impaired aquatic communities. However, the responses of communities and associated nutrient cycling processes to periodic thermal stratification are still poorly understood. This study delved into the changes in water quality, algal-bacterial communities, and functional diversity influenced by thermal stratification succession, and their relationship with nutrient cycling. The results indicated that the apparent community dynamics were driven by environmental factors, with ammonium (NH4+) and nitrate (NO3--N) being the most important factors that influenced the algal and bacterial community structure, respectively. Ecological niche widths were narrower during thermal stratification, exacerbating the antagonism of the communities, and stochastic processes dominated community assembly. Then, the complexities of the co-occurrence network decreased with succession. Algal community assembly became more deterministic, while bacterial assembly became more stochastic. Moreover, the roles of algal-bacterial multidiversity in nutrient cycling differed: bacterial diversity enhanced nutrient cycling, whereas algal diversity had the opposite effect. These findings broadened our understanding of microbial ecological mechanisms to environmental change and provided valuable ecological knowledge for securing water supplies in drinking water reservoirs.

Co-assembled whey protein and proanthocyanidins as a promising biocarrier for hydrophobic pterostilbene: Fabrication, characterization, and cellular antioxidant potential.

The usage of food-derived polyphenols with different polarities has been limited by their instability and incompatibility. Therefore, a biocarrier was developed by co-assembly of whey protein isolate (WPI) and hydrophilic proanthocyanidin (PC) for loading hydrophobic pterostilbene (PTE). Such biocarrier has superior affinity for PTE than WPI alone, as determined by encapsulation efficiency and loading capacity assay, fluorescence quenching analysis, and molecular docking, whereas the assembly process was characterized by particle size and zeta potential, 3-dimensional fluorescence, and scanning electron microscopy. Circular dichroism and Fourier transform infrared spectroscopy spectra confirmed the α-helix to ß-sheet and random coil transition of proteins during the formation of nanocomplexes. Whey protein isolate acted as a mediator through altering the binding mode of PC and PTE, allowing them to perform significant synergistic effects in enhancing 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl radical scavenging and reducing H2O2-induced cell damage. This research may serve to develop new protein/polyphenol co-loading systems and offer a reliable nutritional fortification.

Tunable Ordered Nanostructured Phases by Co-assembly of Amphiphilic Polyoxometalates and Pluronic Block Copolymers.

The assembly of polyoxometalate (POM) metal-oxygen clusters into ordered nanostructures is attracting a growing interest for catalytic and sensing applications. However, assembly of ordered nanostructured POMs from solution can be impaired by aggregation, and the structural diversity is poorly understood. Here, we present a time-resolved small-angle X-ray scattering (SAXS) study of the co-assembly in aqueous solutions of amphiphilic organo-functionalized Wells-Dawson-type POMs with a Pluronic block copolymer over a wide concentration range in levitating droplets. SAXS analysis revealed the formation and subsequent transformation with increasing concentration of large vesicles, a lamellar phase, a mixture of two cubic phases that evolved into one dominating cubic phase, and eventually a hexagonal phase formed at concentrations above 110 mM. The structural versatility of co-assembled amphiphilic POMs and Pluronic block copolymers was supported by dissipative particle dynamics simulations and cryo-TEM.

Co-Assembled Supramolecular Organohydrogels of Amphiphilic Zwitterion and Polyoxometalate with Controlled Microstructures.

The organization of modifiable and functional building components into various superstructures is of great interest due to their broad applications. Supramolecular self-assembly, based on rationally designed building blocks and appropriately utilized driving forces, is a promising and widely used strategy for constructing superstructures with well-defined nanostructures and diverse morphologies across multiple length scales. In this study, two homogeneous organohydrogels with distinct appearances were constructed by simply mixing polyoxometalate (phosphomolybdic acid, HPMo) and a double-tailed zwitterionic quaternary ammonium amphiphile in a binary solvent of water and dimethyl sulfoxide (DMSO). The delicate balance between electrostatic attraction and repulsion of anionic HPMo clusters and zwitterionic structures drove them to co-assemble into homogeneous organohydrogels with diverse microstructures. Notably, the morphologies of the organohydrogels, including unilamellar vesicles, onion-like vesicles, and spherical aggregates, can be controlled by adjusting the ionic interactions between the zwitterionic amphiphiles and phosphomolybdic acid clusters. Furthermore, we observed an organohydrogel fabricated with densely stacked onion-like structures (multilamellar vesicles) consisting of more than a dozen layers at certain proportions. Additionally, the relationships between the self-assembled architectures and the intermolecular interactions among the polyoxometalate, zwitterionic amphiphile, and solvent molecules were elucidated. This study offers valuable insights into the mechanisms of polyoxometalate-zwitterionic amphiphile co-assembly, which are essential for the development of materials with specific structures and emerging functionalities.

Topology of Gemini-shaped Hexagonal Heterojunction for Efficient Stereoconvergent Transformation via Dynamic Kinetic Resolution.

Despite recent advances in the combination of kinetic resolution and racemization for efficient stereoconvergent transformation, the poor stability and limited reaction activities of the products restrict their wide application in industrial production. To overcome these problems, Gemini-shaped hexagons with para-heterojunctions for one-dimensional and two-dimensional supramolecular polymers were designed via hydrogen-bonding adhesion by racemization catalyst 1 and kinetic resolution 2 in this work. The polymers from the assembly of Gemini-shaped hexagons exhibit rapid catalytic behaviour with efficient selectivity for the desired configuration in the synthesis of tertiary alcohols with contiguous stereocenters through dynamic kinetic resolution for the nanoscale heterojunctions of dissimilar catalysts. Among them, the developed 2D polymers gave outstanding enantioselectivities and diastereoselectivities (>99% ee, 20:1 dr) through the cooperation of adjacent dissimilar catalysts. The heterojunctions varying dimensions and distances of dissimilar catalysts provide new insight for increasing the enantioselectivity of chiral organocatalysts.

Fabrication of Hierarchical Nanostructures featuring Amplified Asymmetry through Co-assembly of Liquid Crystalline Block Copolymer and Chiral Amphiphiles.

The widespread presence of hierarchical asymmetric structures in nature has sparked considerable interest because of their unique functionalities. These ingenious structures across multiple scales often emerge from the transfer and amplification of asymmetry from chiral molecules under various synergistic effects. However, constructing artificial chiral asymmetric structures, particularly in developing hierarchical multicomponent structures analogous to those formed in nature through synergistic non-covalent interactions, still presents tremendous challenges. Herein, we propose a co-assembly strategy to fabricate hierarchical chiral mesostructures by combining a liquid crystalline block copolymer (LC-BCP) with a small molecular amphiphile containing chiral alanine or phenylalanine as a linker. Through a classic solvent-exchange process, chiral amphiphiles embedded within LC-BCP finely regulate the LC ordering effect and facilitate transfer and amplification of asymmetry. Consequently, various co-assembled structures with significant hierarchical chirality features are obtained through synergetic effects. Remarkably, subtle alterations to the side groups of amino acids in the amphiphiles effectively adjust the hierarchical morphology transition. Moreover, the covalent bonding sequence of amino acids in the amphiphiles emerges as a critical factor governing the formation of hierarchical nanofibers and multilayered vesicles exhibiting a superhelical sense.

Co-Assembly of Carbon Nanotube Porins into Biomimetic Peptoid Membranes.

Robust and cost-effective membrane-based separations are essential to solving many global crises, such as the lack of clean water. Even though the current polymer-based membranes are widely used for separations, their performance and precision can be enhanced by using a biomimetic membrane architecture that consists of highly permeable and selective channels embedded in a universal membrane matrix. Researchers have shown that artificial water and ion channels, such as carbon nanotube porins (CNTPs), embedded in lipid membranes can deliver strong separation performance. However, their applications are limited by the relative fragility and low stability of the lipid matrix. In this work, we demonstrate that CNTPs can co-assemble into two dimension (2D) peptoid membrane nanosheets, opening up a way to produce highly programmable synthetic membranes with superior crystallinity and robustness. A combination of molecular dynamics (MD) simulations, Raman spectroscopy, X-ray diffraction (XRD), and atomic force microscopy (AFM) measurements to verify the co-assembly of CNTP and peptoids are used and show that it does not disrupt peptoid monomer packing within the membrane. These results provide a new option for designing affordable artificial membranes and highly robust nanoporous solids.

Freestanding, Freeform Metamolecule Fibers Tailoring Artificial Optical Magnetism.

Metamolecule clusters support various unique types of artificial electromagnetism at optical frequencies. However, the technological challenges regarding the freeform fabrication of freestanding metamolecule clusters with programmed geometries and multiple compositions remain unresolved. Here, the freeform, freestanding raspberry-like metamolecule (RMM) fibers based on the directional guidance of a femtoliter meniscus are presented, resulting in the evaporative co-assembly of silica nanoparticles and gold nanoparticles with the aid of 3D nanoprinting. This method offers a facile and universal pathway to shape RMM fibers in 3D, enabling versatile manipulation of near- and far-field characteristics. In particular, the authors demonstrate the ability to decrease the scattering of the millimeter-scale RMM fiber in visible spectrum. In addition, the influence of electric and magnetic dipole modes on the directional scattering of RMM fibers is investigated. These experiments show that the magnetic response of an individual RMM can be controlled by adjusting the filling factor of gold nanoparticles. The authors anticipate that this method will allow for unrestricted design and realization of nanophotonic structures, surpassing the limitations of conventional fabrication processes.

Controlling the Morphological Features, Aspect Ratio and Emission Patterns of Supramolecular Copolymers by Restricted Dimensional Growth.

One of the bottlenecks associated with supramolecular polymerization of functional π-systems is the spontaneous assembly of monomers leading to one- or two-dimensional (1D or 2D) polymers without control over chain length and optical properties. In the case of supramolecular copolymerization of monomers that are structurally too diverse, preferential self-sorting occurs unless they are closely interacting donor-acceptor pairs. Herein, it is established that the spontaneous 1D polymerization of a phenyleneethynylene (PE) derivative and the 2D polymerization of a Bodipy derivative (BODIPY) can be controlled by copolymerizing them in different ratios, leading to unusual spindle-shaped structures with controlled aspect ratio, as evident by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM) studies. For example, when the content of BODIPY is 50 % in the BODIPY-PE mixture, the 1D polymerization of PE is significantly restricted to form elongated spindle-like structures having an aspect ratio of 4-6. The addition of 75 % of BODIPY to PE resulted in circular spindles having an aspect ratio of 1-2.5, thereby completely restricting the 1D polymerization of PE monomers. Moreover, the resultant supramolecular copolymers exhibited morphology and aspect ratio dependent emission features as observed by the time-resolved emission studies.

Hierarchically Organized Cocrystal of Tetra-Anionic Porphyrin and Di-Cationic Viologen: Ion Conformations, Supramolecule Interactions, and Porphyrin Arrays.

Ionic co-assembly of tetra-anionic porphyrins has been extensively researched in the construction of hierarchically organized architectures with potential application value in organic semiconductors, sunlight catalysts and supramolecular chirality systems. However, such architectures are difficult to grow to a size suitable for single-crystal X-ray diffraction (SCXRD); the lack of single-crystal structures of these architectures leads to challenges in gaining deeper comprehension about that. This study reports a hierarchically organized cocrystal of meso-tetra(4-sulfonato-phenyl)-porphyrin (TSPP4- ) and N, N'-diethyl-viologen (DEV2+ ), wherein wave-like and saddle-like TSPP4- ions co-aggregate at a stoichiometric ratio of 1 : 2 to form unique porphyrin arrays; the spectrum characteristics and calculated coulombic exciton coupling energy show that these porphyrin arrays are J-aggregates. We prove that the distortion of porphyrin ring of TSPP4- strongly correlates with the deflection of its phenyl groups. The crystal comprises six different ionic conformations, and the multiplicity of ionic conformation leads to intricate supramolecular interactions.

Process Dependent Complexity in Multicomponent Gels.

Mixing low molecular weight gelators (LMWGs) can be used to combine favorable properties of the individual components within a multifunctional gel. Such multicomponent systems are complex enough in themselves but the method of combining components is not commonly considered something to influence self-assembly. Herein, two multicomponent systems comprising of a naphthalene-based dipeptide hydrogelator and one of two modified naphthalene diimides (NDIs), one of which forms gels, and the other does not, are investigated. These systems are probed, examining the structures formed and their gel properties (when preparing a solution from either a mixed powder of both components or by mixing pre-formed solutions of each component) using rheology, small angle neutron scattering (SANS), and absorbance spectroscopy. It is found that by altering the method of preparation, it is can either induce self-sorting or co-assembly within the fibers formed that underpin the gel network.

P-Selectin mediates targeting of a self-assembling phototherapeutic nanovehicle enclosing dipyridamole for managing thromboses.

Thrombotic vascular disorders, specifically thromboembolisms, have a significant detrimental effect on public health. Despite the numerous thrombolytic and antithrombotic drugs available, their efficacy in penetrating thrombus formations is limited, and they carry a high risk of promoting bleeding. Consequently, the current medication dosage protocols are inadequate for preventing thrombus formation, and higher doses are necessary to achieve sufficient prevention. By integrating phototherapy with antithrombotic therapy, this study addresses difficulties related to thrombus-targeted drug delivery. We developed self-assembling nanoparticles (NPs) through the optimization of a co-assembly engineering process. These NPs, called DIP-FU-PPy NPs, consist of polypyrrole (PPy), dipyridamole (DIP), and P-selectin-targeted fucoidan (FU) and are designed to be delivered directly to thrombi. DIP-FU-PPy NPs are proposed to offer various potentials, encompassing drug-loading capability, targeted accumulation in thrombus sites, near-infrared (NIR) photothermal-enhanced thrombus management with therapeutic efficacy, and prevention of rethrombosis. As predicted, DIP-FU-PPy NPs prevented thrombus recurrence and emitted visible fluorescence signals during thrombus clot penetration with no adverse effects. Our co-delivery nano-platform is a simple and versatile solution for NIR-phototherapeutic multimodal thrombus control.

Hetero-pentamerization determines mobility and conductance of Glycine receptor α3 splice variants.

Glycine receptors (GlyRs) are ligand-gated pentameric chloride channels in the central nervous system. GlyR-α3 is a possible target for chronic pain treatment and temporal lobe epilepsy. Alternative splicing into K or L variants determines the subcellular fate and function of GlyR-α3, yet it remains to be shown whether its different splice variants can functionally co-assemble, and what the properties of such heteropentamers would be. Here, we subjected GlyR-α3 to a combined fluorescence microscopy and electrophysiology analysis. We employ masked Pearson's and dual-color spatiotemporal correlation analysis to prove that GlyR-α3 splice variants heteropentamerize, adopting the mobility of the K variant. Fluorescence-based single-subunit counting experiments revealed a variable and concentration ratio dependent hetero-stoichiometry. Via cell-attached single-channel electrophysiology we show that heteropentamers exhibit currents in between those of K and L variants. Our data are compatible with a model where α3 heteropentamerization fine-tunes mobility and activity of GlyR-α3 channels, which is important to understand and tackle α3 related diseases.