High-Safety Electrolytes with an Anion-Rich Solvation Structure Tuned by Difluorinated Cations for High-Voltage Lithium Metal Batteries.

As next-generation energy storage devices, lithium metal batteries (LMBs) must offer high safety, high-voltage resistance, and a long life span. Electrolyte engineering is a facile strategy to tailor the interfacial chemistry of LMBs. In particular, the solvation structure and derived solid electrolyte interphase (SEI) are crucial for a satisfactory battery performance. Herein, a novel middle-concentrated ionic liquid electrolyte (MCILE) with an anion-rich solvation structure tuned by difluorinated cations is demonstrated to achieve ultrahigh safety, high-voltage stability, and excellent ternary-cathode compatibility. Novel gem-difluorinated cations first synthesized for prestoring fluorine on positively charged species, not only preferentially adsorb in the inner-Helmholtz layers, but also participate in regulating the Li+ solvation structure, resulting in a robust interphase. Moreover, these weak interactions in the Li+ solvation structure including anion-solvent and ionic liquid (IL) cation-solvent pairs are first revealed, which are beneficial for promoting an anion-dominated solvation structure and the desolvation process. Benefiting from the unique anion-rich solvation structure, a stable hetero-SEI structure is obtained. The designed MCILE exhibits compatibility with Li metal anode and the high-voltage ternary cathode at high temperatures (60 °C). This work provides a new approach for regulating the solvation structure and electrode interphase chemistry of LMBs via difluorinated IL cations.

Water-Soluble Chiral Cyclic Peptoids and Their Sodium and Gadolinium Complexes: Study of Conformational and Relaxometric Properties.

Cyclic peptoids are macrocyclic oligomers of N-substituted glycines with specific folding abilities and excellent metal binding properties. In this work, we show how strategic positioning of chiral (S)- and (R)-(1-carboxyethyl)glycine units influences the conformational stability of water-soluble macrocyclic peptoids as sodium complexes. The reported results are based on nuclear magnetic resonance spectroscopy, extensive computational studies, and X-ray diffraction analysis using single crystals grown from aqueous solutions. The studies include 1H relaxometric investigations of hexameric cyclic peptoids in the presence of the Gd3+ ion to assess their thermodynamic stabilities and relaxivities.

Evaluating the Conformations and Dynamics of Peptoid Macrocycles.

Peptoid macrocycles are versatile and chemically diverse peptidomimetic oligomers. However, the conformations and dynamics of these macrocycles have not been evaluated comprehensively and require extensive further investigation. Recent studies indicate that two degrees of freedom, and four distinct conformations, adequately describe the behavior of each monomer backbone unit in most peptoid oligomers. On the basis of this insight, we conducted molecular dynamics simulations of model macrocycles using an exhaustive set of idealized possible starting conformations. Simulations of various sizes of peptoid macrocycles yielded a limited set of populated conformations. In addition to reproducing all relevant experimentally determined conformations, the simulations accurately predicted a cyclo-octamer conformation for which we now present the first experimental observation. Sets of three adjacent dihedral angles (ϕi, ψi, ωi+1) exhibited correlated crankshaft motions over the course of simulation for peptoid macrocycles of six residues and larger. These correlated motions may occur in the form of an inversion of one amide bond and the concerted rotation of the preceding ϕ and ψ angles to their mirror-image conformation, a variation on "crankshaft flip" motions studied in polymers and peptides. The energy landscape of these peptoid macrocycles can be described as a network of conformations interconnected by transformations of individual crankshaft flips. For macrocycles of up to eight residues, our mapping of the landscape is essentially complete.

Programmed Supramolecular Assemblies Using Orthogonal Pairs of Heterodimeric Coiled Coil Peptides.

Despite recent progress, it remains challenging to program biomacromolecules to assemble into discrete nanostructures with pre-determined sizes and topologies. We report here a novel strategy to address this challenge. By using two orthogonal pairs of heterodimeric coiled coils as the building blocks, we constructed six discrete supramolecular assemblies, each composed of a prescribed number of coiled coil components. Within these assemblies, different coiled coils were connected via end-to-side covalent linkages strategically pre-installed between the non-complementary pairs. The overall topological features of two highly complex assemblies, a "barbell" and a "quadrilateral" form, were characterized experimentally and were in good agreement to the designs. This work expands the design paradigms for peptide-based discrete supramolecular assemblies and will provide a route for de novo fabrication of functional protein materials.

Hydroxyethyl Starch Curcumin Enhances Antiproliferative Effect of Curcumin Against HepG2 Cells via Apoptosis and Autophagy Induction.

It is well documented that curcumin (CUR), as a polyphenol molecule originated from turmeric, has many advantages such as antioxidative, anti-inflammatory, neuroprotective, and antitumor effects. However, because of its poor water solubility and low bioavailability, the biomedical applications of CUR are limited. So, in this study, we modified CUR with conjugation to a food-derived hydrophilic hydroxyethyl starch (HES) via an ester linkage to fabricate the amphiphilic conjugate HES-CUR prior to self-assembling into uniform nanoparticles (HES-CUR NPs). And, the results of the 1H NMR spectra and FT-IR spectrum showed successful synthesis of HES-CUR NPs; moreover, the solubility and the drug loading efficiency of CUR were significantly increased. Next, we further explored the differences on the antitumor effects between HES-CUR NPs and CUR in HepG2 cells, and the results of the CCK8-assay and cell counting experiment showed that HES-CUR NPs exhibited a more significant antiproliferative effect than that of CUR in HepG2 cells. And HepG2 cells were more sensitive to apoptosis induced by HES-CUR NPs as evidenced by flow cytometry, increased cytochrome c level, and decreased full length caspase-3 and Bcl-2 protein expressions. Additionally, we found that the efficacy of HES-CUR NPs against HepG2 cells might be related to the enhanced degree of mitochondrial damage (decrease of the mitochondrial membrane potential and ATP) and autophagy (increased levels of Beclin-1 and LC3-II proteins). So, the findings in this study suggest that HES-CUR NPs have a great application potential in antitumor efficacy and play an important role in multiple signal pathways.

Malformin C, an algicidal peptide from marine fungus Aspergillus species.

A natural compound with the algicidal effect was isolated from the culture medium of Aspergillus sp. SCSIOW2 and was identified as malformin C, which was based on the data of 1H-NMR, 13C-NMR, and ESI-MS. Malformin C exhibited dose-dependent algicidal activities against two strains of noxious red tide algae, Akashiwo sanguinea and Chattonella marina. The activity against A. sanguinea was stronger than that against C. marina (the algicidal activity of 58 and 36% at 50 µM treatment for 2 h, respectively). Morphology changes including perforation, plasmolysis, and fragmentation of algal cells were observed. Malformin C induced a significant increase in ROS level, caused the damage of SOD activity, and led to the massive generation of MDA contents in algae cells. To our knowledge, this is the first report of the cyclic peptide described as an algicidal compound against HABs.

Self-assembly of chimeric peptides toward molecularly defined hexamers with controlled multivalent ligand presentation.

This work demonstrates a self-assembling peptide strategy to form finite, molecularly defined trigonal bipyramidal-like hexamers which offer control over multivalent ligand display for enhanced tumor targeting.

A modular approach for organizing dimeric coiled coils on peptoid oligomer scaffolds.

We report a general approach to promote the folding of synthetic oligopeptides capable of forming homodimeric coiled coil assemblies. By pre-organizing the peptides on macrocyclic oligomer scaffolds, the stability of the coiled coils is enhanced with an observed increase in the melting temperature of 30 °C to 40 °C. Molecular dynamics simulations substantiate the hypothesis that the enhanced stability is established by constraining motion at the peptide termini and by pre-organizing intramolecular helix-helix contacts. We demonstrate the modularity of this approach by using a family of peptoid scaffolds to promote the folding of a dimeric coiled coil. Importantly, this strategy for templating coiled coils allows preservation of native amino acid sequences. Comparing a macrocyclic peptoid scaffold to its linear counterparts indicates that both types of assemblies are effective for organizing stable coiled coils. These results will guide future designs of coiled coil peptides for biomedical applications and as building blocks for more complex supramolecular assemblies.

Isomeric Ir(iii) complexes for tracking mitochondrial pH fluctuations and inducing mitochondrial dysfunction during photodynamic therapy.

Mitochondrial pH is known to be alkaline (near 8.0) and has emerged as a potential factor for mitochondrial function and disorder. Here we investigate two pairs of isomeric phosphorescent Ir(iii) complexes (1-4) that show mitochondrial pH-responsive properties and induce mitochondrial dysfunction during photodynamic therapy. These complexes are designed to function by controlling the protonation of the benzimidazole and carboxyl groups. 1 and 2 exhibit enhanced emission intensity and a blue-shift emission change in response to pH alterations from 6.0 to 8.0. They have ideal pKa values (7.49 for 1 and 7.41 for 2) and show mitochondria-specific phosphorescence staining in situ, thereby allowing the monitoring of mitochondrial pH in live cells. 3 and 4 produce abundant intracellular ROS and exhibit high phototoxicities against cancer cells. Interestingly, these pH-responsive probes can be utilized to monitor the change in mitochondrial pH and mitochondrial damage during photodynamic therapy (PDT), which provides a convenient method for the in situ monitoring of therapeutic effects and the assessment of treatment outcomes.

A facile approach for the synthesis of nido-carborane fused oxazoles via one pot deboronation/cyclization of 9-amide-o-carboranes.

A one pot deboronation/cyclization of 9-amide-o-carboranes for the synthesis of nido-7,8-carborane fused oxazole by cooperation of Pd(OAc)2, AgOAc and K2CO3 has been developed. A plausible mechanism involving an amide directed electrophilic palladation of the B-H bond and deboronation/cyclization process was proposed based on the successful isolation and structural characterization of the key deboronated intermediate.

Palladium catalyzed selective arylation of o-carboranes via B(4)-H activation: amide induced regioselectivity reversal.

By changing the charge distribution of boron vertices via introducing an amide on cage B(9), the selective B(4) arylation of o-carboranes via Suzuki-Miyaura coupling has been developed. A series of o-carborane derivatives decorated with diverse active groups have been synthesized with moderate to good yields, which have been proved to be further transformed to a novel kind of tri-substituted nido-carborane fused oxazole with potential application in boron neutron capture therapy, organometallic as well as coordination chemistry.

Shape-specific nanostructured protein mimics from de novo designed chimeric peptides.

Natural proteins self-assemble into highly-ordered nanoscaled architectures to perform specific functions. The intricate functions of proteins have provided great impetus for researchers to develop strategies for designing and engineering synthetic nanostructures as protein mimics. Compared to the success in engineering fibrous protein mimetics, the design of discrete globular protein-like nanostructures has been challenging mainly due to the lack of precise control over geometric packing and intermolecular interactions among synthetic building blocks. In this contribution, we report an effective strategy to construct shape-specific nanostructures based on the self-assembly of chimeric peptides consisting of a coiled coil dimer and a collagen triple helix folding motif. Under salt-free conditions, we showed spontaneous self-assembly of the chimeric peptides into monodisperse, trigonal bipyramidal-like nanoparticles with precise control over the stoichiometry of two folding motifs and the geometrical arrangements relative to one another. Three coiled coil dimers are interdigitated on the equatorial plane while the two collagen triple helices are located in the axial position, perpendicular to the coiled coil plane. A detailed molecular model was proposed and further validated by small angle X-ray scattering experiments and molecular dynamics (MD) simulation. The results from this study indicated that the molecular folding of each motif within the chimeric peptides and their geometric packing played important roles in the formation of discrete protein-like nanoparticles. The peptide design and self-assembly mechanism may open up new routes for the construction of highly organized, discrete self-assembling protein-like nanostructures with greater levels of control over assembly accuracy.

Palladium catalyzed/silver tuned selective mono-/tetra-acetoxylation of o-carboranes via B-H activation.

A palladium catalyzed/silver tuned selective mono- and tetra-acetoxylation of o-carboranes has been developed, and a series of mono- and tetra-acetoxylated o-carboranes decorated with active groups have been synthesized with moderate to good yields as well as excellent selectivity. A mechanism involving electrophilic palladation and cyclopalladation of the B-H bond was proposed.

Protein-like Nanoparticles Based on Orthogonal Self-Assembly of Chimeric Peptides.

A novel two-component self-assembling chimeric peptide is designed where two orthogonal protein folding motifs are linked side by side with precisely defined position relative to one another. The self-assembly is driven by a combination of symmetry controlled molecular packing, intermolecular interactions, and geometric constraint to limit the assembly into compact dodecameric protein nanoparticles.

Membrane activity of a supramolecular peptide-based chemotherapeutic enhancer.

Self-assembly of de novo designed multidomain peptides (MDPs) resulted in functional membrane-active supramolecular nanofibers. The membrane activity was analyzed through fluorescence membrane localization and patch-clamp electrophysiology yielding important information that can be used for the development of a new type of supramolecular peptide-based chemotherapeutic enhancer.

Electric-Assisted Capillary Rise Adsorption of Polar and Nonpolar Solvents by Cellulose and Chitosan.

Electric-assisted capillary rise adsorption of polar and nonpolar solvents by cellulose and chitosan was studied by employing an electrostatic generator to assist a common capillary rise wetting by taking the anode and cathode electrodes respectively linked to a metal tube charged with samples and the probe solvent. To vary the voltage at 0, 100, 200, and 300 V, respectively, the recorded dynamic adsorption results showed that the cellulose and chitosan both kept a stable adsorption of the nonpolar hexane and diiodomethane, obviously ignoring the voltage increase. Moreover, the hexane amount adsorbed by cellulose and chitosan is similar, while the diiodomethane amount was adsorbed to a greater amount by cellulose as compared with the chitosan corresponding to these two biomaterials-based nonpolar components, for example, greater for cellulose and smaller for chitosan. Results also showed that the adsorption of polar water and formamide was gradually increased with the voltage increase, especially for chitosan, to correspond to the polar component of these materials, for example, greater for chitosan and smaller for cellulose. These adsorption behaviors suggested that the application of an extra electric field can only enhance the adsorption of polar solvent, and the molecular structure, for exmaple, the ß-(1-4)-linked d-glucosamine units of chitosan, has sensitive electric field responses in polar solvent adsorption as compared with those of the ß(1-4)-linked d-glucose units of cellulose. The reason for the electric adsorption behaviors was known due to the presence of an extra electric-field-induced reduction of the total surface tension of solvent and mainly the polar component.

Exploiting hydrophobic borohydride-rich ionic liquids as faster-igniting rocket fuels.

A family of hydrophobic borohydride-rich ionic liquids was developed, which exhibited the shortest ignition delay times of 1.7 milliseconds and the lowest viscosity (10 mPa s) of hypergolic ionic fluids, demonstrating their great potential as faster-igniting rocket fuels to replace toxic hydrazine derivatives in liquid bipropellant formulations.

Self-assembly of cationic multidomain peptide hydrogels: supramolecular nanostructure and rheological properties dictate antimicrobial activity.

Hydrogels are an important class of biomaterials that have been widely utilized for a variety of biomedical/medical applications. The biological performance of hydrogels, particularly those used as wound dressing could be greatly advanced if imbued with inherent antimicrobial activity capable of staving off colonization of the wound site by opportunistic bacterial pathogens. Possessing such antimicrobial properties would also protect the hydrogel itself from being adversely affected by microbial attachment to its surface. We have previously demonstrated the broad-spectrum antimicrobial activity of supramolecular assemblies of cationic multi-domain peptides (MDPs) in solution. Here, we extend the 1-D soluble supramolecular assembly to 3-D hydrogels to investigate the effect of the supramolecular nanostructure and its rheological properties on the antimicrobial activity of self-assembled hydrogels. Among designed MDPs, the bactericidal activity of peptide hydrogels was found to follow an opposite trend to that in solution. Improved antimicrobial activity of self-assembled peptide hydrogels is dictated by the combined effect of supramolecular surface chemistry and storage modulus of the bulk materials, rather than the ability of individual peptides/peptide assemblies to penetrate bacterial cell membrane as observed in solution. The structure-property-activity relationship developed through this study will provide important guidelines for designing biocompatible peptide hydrogels with built-in antimicrobial activity for various biomedical applications.

Designed filamentous cell penetrating peptides: probing supramolecular structure-dependent membrane activity and transfection efficiency.

In this work, we will demonstrate a simple yet powerful strategy to assemble single-chain cationic peptides into macromolecular filamentous nanostructures with dramatically improved membrane activity, stability and transfection efficiency.

Designed supramolecular filamentous peptides: balance of nanostructure, cytotoxicity and antimicrobial activity.

This work demonstrates a design strategy to optimize antimicrobial peptides with an ideal balance of minimal cytotoxicity, enhanced stability, potent cell penetration and effective antimicrobial activity, which hold great promise for the treatment of intracellular microbial infections and potentially systemic anti-infective therapy.