Spatiotemporal control and superselectivity in supramolecular polymers using multivalency

Multivalency has an important but poorly understood role in molecular self-organization. We present the noncovalent synthesis of a multicomponent supramolecular polymer in which chemically distinct monomers spontaneously coassemble into a dynamic, functional structure. We show that a multivalent recruiter is able to bind selectively to one subset of monomers (receptors) and trigger their clustering along the self-assembled polymer, behavior that mimics raft formation in cell membranes. This phenomenon is reversible and affords spatiotemporal control over the monomer distribution inside the supramolecular polymer by superselective binding of single-strand DNA to positively charged receptors. Our findings reveal the pivotal role of multivalency in enabling structural order and nonlinear recognition in water-soluble supramolecular polymers, and it offers a design principle for functional, structurally defined supramolecular architectures.     

Pd0@Polyoxometalate Nanostructures as Green Electrocatalysts: Illustrative Example of Hydrogen Production

Green-chemistry type procedures were used to synthesize Pd⁰ nanostructures encapsulated by a vanadium-substituted Wells-Dawson-type polyoxometalate (Pd⁰@POM). The cyclic voltammogram run with the Pd⁰@POM-modified glassy carbon electrode shows well-defined waves, associated with Pd⁰ nanostructures and the V^V/V^IV redox couple. The Pd⁰@POM-modified electrode displayed remarkably reproducible cyclic voltammetry patterns. The hydrogen evolution reaction (HER) was selected as an illustrative example to test the electrocatalytic behavior of the electrode. The kinetic parameters of the HER show the high efficiency of the Pd⁰@POM-modified electrode. This is the first example of electrochemical characterization of a modified electrode based on a vanado-tungstic POM and Pd⁰ nanostructures.     

Dynamic hybrid materials for constitutional self-instructed membranes

Constitutional self-instructed membranes were developed and used for mimicking the adaptive structural functionality of natural ion-channel systems. These membranes are based on dynamic hybrid materials in which the functional self-organized macrocycles are reversibly connected with the inorganic silica through hydrophobic noncovalent interactions. Supramolecular columnar ion-channel architectures can be generated by reversible confinement within scaffolding hydrophobic silica mesopores. They can be structurally determined by using X-ray diffraction and morphologically tuned by alkali-salts templating. From the conceptual point of view, these membranes express a synergistic adaptive behavior: the simultaneous binding of the fittest cation and its anion would be a case of “homotropic allosteric interactions,” because in time it increases the transport efficiency of the pore-contained superstructures by a selective evolving process toward the fittest ion channel. The hybrid membranes presented here represent dynamic constitutional systems evolving over time to form the fittest ion channels from a library of molecular and supramolecular components, or selecting the fittest ion pairs from a mixture of salts demonstrating flexible adaptation.     

Supramolecular Behavior of the Amphiphilic Drug (2<Emphasis Type="Italic">R</Emphasis>)-2-Ethylchromane-2-Carboxylic Acid Arginine Salt (a Novel PPARα/γ Dual Agonist)

Purpose This study was conducted to evaluate the aggregation properties of an amphiphilic drug.Methods Aggregation of the drug was studied by various methods including phase-contrast and polarized microscopy, spectrophotometry, surface tensiometry, atomic force microscopy, and dynamic light scattering. Lymph-cannulated rats were used to assess fractions of drug that were absorbed into lymphatics.Results During the pharmaceutical development of an α/γ dual PPAR agonist, a derivative of a chromane-2-carboxylic acid (compound 1), it was discovered that the compound was able to form various aggregates in aqueous media from pH 6.5 to 7.1, whereas aggregating predominantly into micelles at higher pH values. Critical micelle concentrations seemed to be quite low, about 0.25 mM (0.17 mg/mL) in deionized water as determined by spectrophotometric (dye) and surface tensiometry (du Nuoy) methods. Aggregation of compound 1 into large supramolecular aggregates was visualized via phase-contrast microscopy and atomic force microscopy. The observed aggregates ranged from 250 nm to greater than 10 μm in size. Formation of liquid crystalline phases was observed by polarized microscopy as the material was gradually hydrated with water. Lymph studies in rats indicated that up to 6.9% of the orally administered dose of compound 1 in pH 6.5 buffer appeared in lymph, suggesting that supramolecular aggregation may also occur in vivo leading to partitioning between the portal and the lymph routes.Conclusions The aforementioned supramolecular aggregation was found to have a profound effect on the pharmaceutical development of the drug and potentially on in vivo absorption of the drug.     

Kinetic Studies and Temperature-Induced Morphological Changes of Peptide Decorated Nano-Objects via Polymerization-Induced Self-Assembly

In the present work, combining polymerization-induced self-assembly (PISA) with self-assembling peptides (SAPs) peptide−polymer hybrid nanostructures are prepared, harnessing the advantages of PISA and the self-assembling driving force of SAPs. A tripeptide methacrylamide denoted as MAm-GFF, where MAm, G, and F stand for methacrylamide, glycine, and phenylalanine, is copolymerized with glycerol monomethacrylate (GMA) by reversible addition−fragmentation chain transfer polymerization (RAFT) in dimethylformamide to produce a P(GMA₆₂-stat-(MAm-GFF)₇) macromolecular chain transfer agent (macro-CTA). This peptide-containing macro-CTA is then successfully chain-extended with poly(2-hydroxypropyl methacrylate) (PHPMA) by aqueous dispersion PISA, forming P(GMA₆₂-stat-(MAm-GFF)₇)-b-PHPMA₂₇ self-assembled objects. The impacts of temperature and monomer conversion on the morphologies formed during the PISA process are investigated by analyzing samples withdrawn at different time during the polymerization of HPMA using transmission electron microscopy (TEM) and dynamic light scattering (DLS) at different temperatures (5–70 °C).     

PLLA-Based Block Copolymers via Raft Polymerization—Impact of the Synthetic Route and Activation Mechanism

Designing supramolecular structures with well-defined dimensions and diverse morphologies via the self-assembly of block copolymers is renowned. Specifically, the design of 1D fiber nanostructures is extensively emphasized, due to their unique properties in many areas, such as microelectronics, photonics, and particularly in the biomedical field. Herein, amphiphilic diblock copolymers of P(l -lactide)-b-P(N-t-butoxy-carbonyl-N´-acryloyl-1,2-diaminoethane)-co-P(N-isopropylacrylamide) PLLA_n-b-P(BocAEAm)_m-co- P(NiPAAm)_Ɩ are developed. Two synthetic strategies are investigated to equip PLLA with a chain transfer agent (CTA), either by Steglich esterification of PLLA-OH or via the ring-opening polymerization of l -lactide using a CTA containing a hydroxyl functional group. The second strategy proves to be superior in terms of degree of functionalization. The corona-forming blocks, with degrees of polymerization of 200 and above are achieved in good definition by photo-iniferter RAFT polymerization (Đ ≤ 1.25), while a Đ of 1.75 is obtained by conventional RAFT polymerization. The self-assembly of the developed system leads to the formation of nanofibers with a height of 11 nm and a length of ≈300 nm, which is determined by atomic force microscopy (AFM). These fibers are the basis for new antimicrobial nanomaterials after deprotection, as the subject of upcoming work.     

Microdome-Tunable Graphene/Carbon Nanotubes Pressure Sensors Based on Polystyrene Array for Wearable Electronics

Resistive pressure sensors are appealing due to having several advantages, such as simple reading mechanisms, simple construction, and quick dynamic response. Achieving a constantly changeable microstructure of sensing materials is critical for the flexible pressure sensor and remains a difficulty. Herein, a flexible, tunable resistive pressure sensors is developed via simple, low-cost microsphere self-assembly and graphene/carbon nanotubes (CNTs) solution drop coating. The sensor uses polystyrene (PS) microspheres to construct an interlocked dome microstructure with graphene/CNTs as a conductive filler. The results indicate that the interlocked microdome-type pressure sensor has better sensitivity than the single microdome-type and single planar-type without surface microstructure. The pressure sensor’s sensitivity can be adjusted by varying the diameter of PS microspheres. In addition, the resistance of the sensor is also tunable by adjusting the number of graphene/CNT conductive coating layers. The developed flexible pressure sensor effectively detected human finger bending, demonstrating tremendous potential in human motion monitoring.     

Facile self-assembly of colloidal diamond from tetrahedral patchy particles via ring selection

Diamond-structured crystals, particularly those with cubic symmetry, have long been attractive targets for the programmed self-assembly of colloidal particles, due to their applications as photonic crystals that can control the flow of visible light. While spherical particles decorated with four patches in a tetrahedral arrangement—tetrahedral patchy particles—should be an ideal building block for this endeavor, their self-assembly into colloidal diamond has proved elusive. The kinetics of self-assembly pose a major challenge, with competition from an amorphous glassy phase, as well as clathrate crystals, leaving a narrow widow of patch widths where tetrahedral patchy particles can self-assemble into diamond crystals. Here we demonstrate that a two-component system of tetrahedral patchy particles, where bonding is allowed only between particles of different types to select even-member rings, undergoes crystallization into diamond crystals over a significantly wider range of patch widths conducive for experimental fabrication. We show that the crystallization in the two-component system is both thermodynamically and kinetically enhanced, as compared to the one-component system. Although our bottom-up route does not lead to the selection of the cubic polytype exclusively, we find that the cubicity of the self-assembled crystals increases with increasing patch width. Our designer system not only promises a scalable bottom-up route for colloidal diamond but also offers fundamental insight into crystallization into open lattices.

Much effort has been placed in devising fabrication routes to diamond-structured colloidal crystals, driven by their applications in visible photonics (1, 2). In this context, the self-assembly of submicrometer colloidal particles has long been recognized as a promising scalable bottom-up approach (3–6). In this endeavor, a variety of designer building blocks with tunable interparticle interactions have been synthesized over the years, leading to recent success in their self-assembly into diamond-structured crystals (7, 8). Although spherical particles decorated with four patches in tetrahedral symmetry appeared as the front-runner to yield a diamond crystal (9, 10), the self-assembly of a diamond crystal from such tetrahedral patchy particles proved challenging.The self-assembly of a diamond crystal from tetrahedral patchy particles faces challenges that can be of both thermodynamic and kinetic origins, as suggested by a number of computer simulation studies (11–14). When the particles possess narrow patches, five-member rings form more readily as compared to six-member rings, and clathrate structures are thus kinetically favored over a diamond structure (14). On the other hand, when patches are too wide, there is not a sufficiently large thermodynamic driving force for spontaneous crystallization to occur (11). A significant degree of supercooling is then required for the free-energy barrier to crystal nucleation to become surmountable to allow for spontaneous crystallization (12). As a result, crystallization is preempted by the dynamic arrest of the system into an amorphous glassy network when the attractive patches are too wide (11, 12, 14). The glassy network has a distribution of rings, including even- and odd-member rings (15). As diamond crystals comprise exclusively even-member rings, the tetrahedral patchy particles become dynamically arrested due to frustration between the local order of the fluid and the global order of the crystal (16).Recent studies have demonstrated that a two-stage self-assembly scheme for triblock patchy particles via tetrahedral clusters promotes crystallization into open crystals, where each particle has a coordination number of six, by suppressing the formation of five- and seven-member rings (17, 18). The frustration caused by a distribution of ring sizes could be a generic mechanism by which crystallization into an open lattice is hindered. In the present computational study, we sought to demonstrate the generality of this hypothesis by investigating the self-assembly of diamond crystals in a system that contains two types of designer tetrahedral patchy particles, each having four identical patches, in a 1:1 mixture. We introduce specific interactions, such that bond formation can only occur between the two different types of particles, labeled A and B. Such specificity in bond formation can be realized using DNA-mediated interactions (19–21). Our tetrahedral patchy particles are represented by the widely used Kern–Frenkel model (22), where particles of different types interact via a combination of a hard-core repulsion, with diameter σ, and a square-well attraction modulated by an angular factor between the patches, with a half-angle θ. The angular factor is unity only when the patches are properly oriented, that is, the vector connecting the centers of the two particles passes through the patches on their surfaces, and zero otherwise. The width of the square well, δ, determines the range of the attraction between the patches relative to the particle diameter and is set to δ=0.2σ. The depth of the square well, ε, governs the strength of the bond. Only hard-sphere repulsion is at play between particles of the same type.Chains of particles in the two-component system considered here can only form closed bond loops in the cases where the first and last particles in the chain are of different species. The contrasting scenarios between the formation of rings in a one-component and a two-component system of tetrahedral patchy particles are shown in Fig. 1 A and B, vividly demonstrating the selection of even-member rings imposed by the constraint of interspecies binding only. The two-component system of tetrahedral patchy particles can, of course, form cubic and hexagonal diamond crystals, representative views of which are shown in Fig. 1 C and D, respectively, and in SI Appendix, Fig. S1. Additionally, we recognize that the two-component system of tetrahedral patchy particles should effectively suppress the formation of s-I and s-II clathrates (both lattices requiring odd-member rings), but it can still stabilize the s-III clathrate, which is composed of four- and six-member rings, as shown in Fig. 1D (23). However, due to the presence of four-member rings, this structure can only form when θ≥9.75°; additionally, the six-member rings found in this structure are planar, as compared to the boat and chair conformations found in the diamond crystals (as shown in Fig. 1 C and D) (11). Due to the frustration associated with the formation of four- and planar six-member rings, we anticipate our design rules for diamond will not suffer any competition from the clathrate s-III crystal.Open in a separate windowFig. 1.Design strategy for the selection of even-member rings in a system of tetrahedral patchy particles using specific interactions. (A) Examples of four-, five-, six-, and seven-member rings that can form in a one-component system of tetrahedral patchy particles. (B) Examples four- and six-member rings that can form in a two-component system of tetrahedral patchy particles, where bonds can form only between distinct species, labeled A (colored yellow) and B (colored pink). Examples of five- and seven-member rings are also shown to highlight that odd-member rings cannot form in such a two-component system of tetrahedral patchy particles, as they require A–A or B–B bonds. (C–E) Example crystal structures that can be stabilized by a two-component system of tetrahedral patchy particles: (C) cubic diamond, (D) hexagonal diamond, and (E) clathrate s-III. The thin black lines represent the edges of the respective unit cells of the crystal structures. We highlight representative six-member rings present in the cubic and hexagonal diamond crystals in the chair and boat conformations, respectively. Additionally, we show the underlying network in the clathrate s-III structure with dashed lines to highlight that the four- and six-member rings in the unit cell are arranged such that they form a truncated octahedron.     

Self-assembled micelles based on gambogenic acid-phospholipid complex for sustained-release drug delivery

Abstract

Objective: To improve the water solubility and enhance the oral bioavailability of gambogenic acid (GNA).

Methods: GNA-phospholipid complex (GNA-PLC) micelles were successfully prepared by anti-solvent method.

Results: The encapsulation efficiency of GNA-PLC micelles can reach 99.33 % (w/w). The average particle size of the GNA-PLC micelles was 291.23?nm which was approximate agreed with the transmission electron microscopy (TEM). In vitro release profile showed the GNA-PLC and GNA-PLC micelles have significant sustained-release of GNA compared with crude GNA. Pharmacokinetic parameters indicated that the area under concentration–time curve (AUC_0→t) of GNA in cases of GNA-PLC and GNA-PLC micelles are 2.04- and 3.92-fold higher than crude GNA, respectively.

Conclusions: The better water solubility and higher bioavailability of GNA in GNA-PLC micelles with significant sustained-release of GNA endow the nanoparticle with great potential in GNA delivery system.     

DNA-Templated Nanowire Fabrication

DNA-based nanotechnology is a vibrant and expanding field. The specific molecular recognition properties and large aspect ratio of DNA make the molecule a promising template for bottom-up fabrication of nanowires and nanodevices. Fabricating well-defined DNA-templated nanowires requires aligned surface deposition and specific metallization of DNA molecules. DNA localization on surfaces has been achieved by bulk fluid flow or a moving air-water interface, and localization efficiency has been improved by surface modifications that favor DNA-substrate interaction. DNA-templated nanowires have been constructed from gold, silver, copper, palladium, and platinum, and template modifications have allowed the bottom-up construction of a simple electronic nanodevice. These achievements demonstrate the promising feasibility of using bottom-up nanofabrication to create increasingly sophisticated nanodevices.