Cluster‐Based Self‐Assembly Route toward MoO3 Single‐Walled Nanotubes

MoO₃ has a unique rigid double‐layer structure, which makes it a real challenge to prepare nanotubular structures. The controlled synthesis of MoO₃ single‐walled nanotubes (SWNTs) is achieved through a cluster‐based self‐assembly route on the dodecanethiol/water interface. Various factors are studied at length, including precursor type, reaction time, temperature, pH value, and their influence on the morphology of products. The concept of “self‐assembly—from simple clusters to nanostructures” is proposed here based on preliminary results from the synthesis of MoO₃ SWNTs, which provides a new aspect for traditional synthetic chemistry of nanomaterials and polyoxometalates.     

Columnar Mesophase Formation of Cyclohexa‐m‐phenylene‐Based Macrocycles

Two novel discotic macrocycles, substituted cyclohexa‐m‐phenylene (CHP) and cyclo‐3,6‐trisphenanthrylene (CTP), and the linear oligomer 3,3′:6′,3′′‐terphenanthrene (TP) as a model substance have been synthesized by repetitive cross‐coupling reactions. To correlate the molecular design with the supramolecular architecture and the established macroscopic order, 2D wide‐angle X‐ray scattering experiments were performed on mechanically extruded filaments. At room temperature in their crystalline phases, all three compounds revealed columnar assemblies in which the macrocycles self‐organized by π‐stacking interactions. The degree of macroscopic order was found to depend upon the planarity and stiffness of the aromatic core. The flexible CHP ring showed a poor macroscopic order of the columnar structures and a low isotropization temperature, whereas the more‐planar, less‐flexible CTP self‐assembled into well‐defined superstructures. The larger π‐stacking area and the more‐pronounced intermolecular interactions for CTP led to the formation of a mesophase over a very large temperature range. The surprising columnar organization of the “open” TP system was explained by back‐folding of the molecule into a ringlike structure.     

Synthesis and Characterisation of Self‐Assembled and Self‐Adjuvanting Asymmetric Multi‐Epitope Lipopeptides of Ovalbumin

Designing a lipopeptide (LP) vaccine with a specific asymmetric arrangement of epitopes may result in an improved display of antigens, increasing host‐cell recognition and immunogenicity. This study aimed to synthesise and characterise the physicochemical properties of a library of asymmetric LP‐based vaccine candidates that contained multiple CD4⁺ and CD8⁺ T‐cell epitopes from the model protein antigen, ovalbumin. These fully synthetic vaccine candidates were prepared by microwave‐assisted solid phase peptide synthesis. The C12 or C16 lipoamino acids were coupled to the N or C terminus of the OVA CD4 peptide epitope. The OVA CD4 LPs and OVA CD8 peptide constructs were then conjugated using azide–alkyne Huisgen cycloaddition to give multivalent synthetic vaccines. Physiochemical characterisation of these vaccines showed a tendency to self‐assemble in aqueous media. Changes in lipid length and position induced self‐assembly with significant changes to their morphology and secondary structure as shown by transmission electron microscopy and circular dichroism.     

Synthesis of Peptide‐Based Hybrid Nanobelts with Enhanced Color Emission by Heat Treatment or Water Induction

We demonstrate that an inorganic lanthanide ion (Tb³⁺) or organic dye molecules were encapsulated in situ into diphenylalanine (FF) organogels by a general, simple, and efficient co‐assembly process, which generated peptide‐based hybrid nanobelts with a range of colored emissions. In the presence of a photosensitizer (salicylic acid), the organogel can serve as an excellent molecular‐donor scaffold to investigate FRET to Tb³⁺. More importantly, heat treatment or water induction instigated a morphology transition from nanofibers to nanobelts, after which the participation of guest molecules in the FF assembly was promoted and the stability and photoluminescence emission of the composite organogels were enhanced.     

Peptide‐Based Methods for the Preparation of Nanostructured Inorganic Materials

With their unique sequence‐specific self‐assembly and their substrate recognition properties, peptides play critical roles in controlling the biomineralization of inorganic nanostructures in natural systems and in directing the assembly of important soft matter. These attributes render them particularly useful molecules for the fabrication of new materials. Researchers from many scientific disciplines now use peptides to direct the synthesis of new inorganic nanostructures and the assembly of soft biomaterials. In this Review we describe the developments in this field and focus on the versatility of peptides and their ability to direct the composition and structure of new inorganic materials.     

Delivery of ROS Generating Anthraquinones Using Reduction‐Responsive Peptide‐Based Nanoparticles

In order to limit the side effects associated with antitumor drugs such as doxorubicin, nanosized drug‐delivery systems capable of selectively delivering and releasing the drug in the diseased tissue are required. We describe nanoparticles (NPs), self‐assembled from a reduction responsive amphiphilic peptide, capable of entrapping high amounts of a redox active anticancer drug candidate and releasing it in presence of a reducing agent. This system shows a high entrapment efficiency with up to 15 mg drug per gram of peptide (5.8 mol‐%). Treatment of the NPs with reducing agent results in the disassembly of the NPs and release of the drug molecules. A reduction in cell viability is observed at drug concentrations above 250 nm in HEK293T and HeLa cell lines. This drug delivery system has potential for targeting tumor sites via the EPR effect while taking advantage of the increased reduction potential in tumor microenvironment.     

Self‐Assembly of a Low‐Symmetry Monodendron Containing Two Asymmetrically Linked Molecular Wedges

Herein, we describe the synthesis of a low‐symmetry monodendron, 3,4‐bis(dodecyloxy)‐5‐[3,4,5‐tris(dodecyloxy)benzyloxy]benzoic acid, following a simple route which starts from gallic acid ethyl ester and does not require any protecting groups. The self‐assembled structures formed by the compound in 3D and 2D were investigated by synchrotron X‐ray scattering and scanning force microscopy (SFM). In 3D, the compound forms a stable crystalline phase with an orthorhombic lattice in which the alkyl chains connected to different benzene rings form crystalline and amorphous domains. Upon cooling from the isotropic melt the compound exhibits a monotropic smectic mesophase. In 100‐nm‐thick films on a neutral substrate the structure loses its biaxiality, adopting a hexagonal columnar structure with the columns oriented parallel to the substrate. By contrast, in ultrathin films on graphite the SFM likely reveals two crystal orientations, which can develop due to the epitaxial adsorption on the substrate of the alkyl chains pertinent to different benzene rings.     

A Self‐Assembling Polythiophene Functionalised with a Cysteine Moiety

A new copolymer bearing a cysteine moiety, designed for molecular interaction, metal‐ion detection, and chiral recognition, was synthesised starting from the dibromo derivative of methyl N‐(tert‐butoxycarbonyl)‐S‐thien‐3‐ylcysteinate and distannylthiophene through a Stille coupling reaction. UV‐vis spectroscopy, circular dichroism, NMR spectroscopy, and gel permeation chromatography analyses evidenced that this polymer is able to form self‐assembling structures, through the formation of a hydrogen‐bond network, not only in the solid state but also in solution.

     

Small‐Peptide‐Based Organogel Kit: Towards the Development of Multicomponent Self‐Sorting Organogels

The results presented here highlight the extremely useful nature of ultra‐short peptides as building blocks in the development of smart multicomponent supramolecular devices. A facile bottom‐up strategy for the synthesis of a small library of stimuli‐responsive smart organogelators has been proposed based on the predictive self‐assembly of ultra‐short peptides. More importantly, the narcissistic self‐sorting of the gelators has been evaluated as a simple method for the efficient co‐assembly of a donor–acceptor dual‐component gel, allowing the investigation of possible future applications of similar systems in the development of a supramolecular photo‐conversion device. Interestingly, it was observed that the self‐organization of the components can lead to highly ordered systems in which discrimination between compatible and non‐compatible building blocks directs the effective organization of the chromophores and gives rise to the formation of an excited‐state complex with exciplex‐like emission. The current report may prove important in the development of organogel‐based multicomponent smart devices.     

Synthesis of Aryldifluoroamides by Copper‐Catalyzed Cross‐Coupling

A copper‐catalyzed coupling of aryl, heteroaryl, and vinyl iodides with α‐silyldifluoroamides is reported. The reaction forms α,α‐difluoro‐α‐aryl amides from electron‐rich, electron‐poor, and sterically hindered aryl iodides in high yield and tolerates a variety of functional groups. The aryldifluoroamide products can be transformed further to provide access to a diverse array of difluoroalkylarenes, including compounds of potential biological interest.     

Multifunctional Porous Microspheres Based on Peptide–Porphyrin Hierarchical Co‐Assembly

Photocatalytically active, multi‐chambered, biomolecule‐based microspheres were prepared by hierarchical co‐assembly of simple dipeptides and porphyrins. The colloidal microspheres are highly hydrated and consist of a network of J‐aggregate nanoscale substructures that serve as light‐harvesting antennae with a relatively broad spectral cross‐section and considerable photostability. These optical properties can be exploited in photocatalytic reactions involving inorganic or organic species. Taken together, these structural and functional features suggest that soft porous biomolecule‐based colloids are a plausible photosynthetic model that could be developed towards demonstrating aspects of primitive abiotic cellularity.     

Hierarchical Structure‐Within‐Structure Morphologies in A2‐star‐(B‐alt‐C) Molecules

We employ dissipative particle dynamics (DPD) to examine the self‐assembly behavior of A₂‐star‐(B‐alt‐C) molecules. We successfully observe various types of hierarchical structure‐within‐structures, such as A‐formed spheres in the matrix formed by B and C alternating layers, hexagonally packed A‐formed cylinders in the matrix with B and C segregated layers, B and C alternating layers‐within‐lamellae, coaxial B and C alternating domains within hexagonally packed BC‐formed cylinders in the A‐matrix, and co‐centric BC‐alternating domains within BC‐formed spheres in the A‐matrix, by increasing the A composition. Generally speaking, the small length‐scale B and C segregated domains are in parallel to the large length‐scale structures. This hierarchical periodicity along the same axis as well as the various characteristic structures, that the A₂‐star‐(B‐alt‐C) copolymers display, are quite different from those in A‐block‐(B‐graft‐C) coil‐comb copolymers. Moreover, it is interesting to find that when the copolymer chain length increases, though the hierarchical structure type is maintained, the number of small length‐scale lamellae that can form within the large length‐scale structure increases. These hierarchical structures under various compositions are reported theoretically for the first time in the copolymer systems consisting of the alternating blocks, and are in good agreement with the most recent experimental work by Matsushita and co‐workers (Macromolecules 2007 , 40, 4023).     

Spin‐Crossover Physical Gels: A Quick Thermoreversible Response Assisted by Dynamic Self‐Organization

Iron(II) triazolate coordination polymers with lipophilic sulfonate counterions with alkyl chains of different lengths have been synthesized. In hydrocarbon solvents, these polymers formed a physical gel and showed a thermoreversible spin transition upon the sol–gel phase transition. The formation of a hydrogen‐bonding network between the triazolate moieties and sulfonate ions, bridged by water molecules, was found to play an important role in the spin‐crossover event. The spin‐transition temperature was tuned over a wide range by adding a small amount of 1‐octanol, a scavenger for hydrogen‐bonding interactions. This additive was essential for the iron(II) species to adopt a low‐spin state. Compared with nongelling references in aromatic solvents, the spin‐crossover physical gels are characterized by their quick thermal response, which is due to a rapid restoration of the hydrogen‐bonding network, possibly because of a dynamic structural ordering through an enhanced lipophilic interaction of the self‐assembling components in hydrocarbon solvents.     

Biology‐Oriented Combined Solid‐ and Solution‐Phase Synthesis of a Macroline‐Like Compound Collection

Macrolines constitute a class of natural products that has more than 100 members and displays diverse biological activities. These compounds feature a cycloocta[b]indole scaffold that represents an interesting target structure for biology‐oriented synthesis (BIOS). We have presented a solid‐phase synthesis of isomerically pure cycloocta[b]indoles by employing the Pictet–Spengler reaction and the Dieckmann cyclization as key steps. The scope of this reaction sequence was investigated in more detail by using various additional diversification procedures, such as Pd‐catalyzed Sonogashira or Suzuki couplings on a solid phase, thus allowing, for example, the generation of 10‐substituted cycloocta[b]indole derivatives. Finally, solution‐phase decoration of the cycloocta[b]indole skeleton by reduction and saponification was evaluated, thereby further extending the scope of the solid‐phase synthesis.     

Amino‐Acid‐Based Block Copolymers by RAFT Polymerization

This review summarizes recent advances in the design and synthesis of amino‐acid‐based block copolymers by reversible addition–fragmentation chain transfer (RAFT) polymerization of amino‐acid‐bearing monomers. We will mainly focus on stimuli‐responsive block copolymers, such as pH‐, thermo‐, and dual‐stimuli‐responsive block copolymers, and self‐assembled block copolymers, including amphiphilic and double‐hydrophilic block copolymers having tunable chiroptical properties. We will also highlight recent results in RAFT synthesis of amino‐acid‐based copolymers having various properties, such as catalytic and optoelectronic properties, cross‐linked block copolymer micelles, unimolecular micelles, and organic–inorganic hybrids.     

Developing Polyamine‐Based Peptide Amphiphiles with Tunable Morphology and Physicochemical Properties

The ability to tune supramolecular properties such as size, morphology, or metabolic stability is of paramount importance in the field of supramolecular chemistry. Peptide amphiphiles (PAs) are a family of functional self‐assembling biomaterials that have garnered widespread attention due to their broad applicability in medicine. PAs are generally comprised of an amino acid sequence connected to lipid tail(s) allowing them to self‐assemble into supramolecular structures with diverse morphologies. Herein, this study describes the synthesis of a new class of polyamine‐based “hybrid” PAs (PPAs) as novel self‐assembling systems. The described molecules possess diverse polyamine head groups with the goal of tuning physicochemical properties. The findings indicate that small changes in the polyamine head groups result in altered PPA morphologies (nanofibers, micelles, nanoworms). The PPAs present a wide range of physicochemical characteristics, show superior resistance to aggregation, a diverse metabolic profile, and varied assembling kinetics. Most of the PPAs do not show toxicity in the human cells lines evaluated. The PPAs described herein hold promising potential as a safe and nontoxic option for drug delivery, targeting, and tissue engineering applications.

     

One‐pot Unsymmetrical Ketone Synthesis Employing a Pyrrole‐Bearing Formal Carbonyl Dication Linchpin Reagent

A one‐pot procedure for the synthesis of unsymmetrical ketones utilizing a pyrrole‐bearing carbonyl linchpin reagent (carbonyl linchpin N,O‐dimethylhydroxylamine pyrrole; CLAmP) is reported. In contrast to other carbonyl dielectrophile equivalents, CLAmP enables the synthesis of ketones from a variety of organolithium and Grignard reagents. The electrophilic nature of CLAmP enables the addition of less reactive as well as thermally unstable nucleophiles. CLAmP was designed to form kinetically stable tetrahedral intermediates upon the addition of organometallic nucleophiles. Evidence for the existence of persistent tetrahedral intermediates was obtained through in situ IR studies.     

Peptide‐Induced Hierarchical Long‐Range Order and Photocatalytic Activity of Porphyrin Assemblies

Long‐range structural order and alignment over different scales are of key importance for the regulation of structure and functionality in biology. However, it remains a great challenge to engineer and assemble such complex functional synthetic systems with order over different length scales from simple biologically relevant molecules, such as peptides and porphyrins. Herein we describe the successful introduction of hierarchical long‐range order in dipeptide‐adjusted porphyrin self‐assembly by a thermodynamically driven self‐orienting assembly pathway associated with multiple weak interactions. The long‐range order and alignment of fiber bundles induced new properties, including anisotropic birefringence, a large Stokes shift, amplified chirality, and excellent photostability as well as sustainable photocatalytic activity. We also demonstrate that the aligned fiber bundles are able to induce the epitaxially oriented growth of Pt nanowires in a photocatalytic reaction.