Secondary‐Structure‐Driven Self‐Assembly of Reactive Polypept(o)ides: Controlling Size,Shape, and Function of Core Cross‐Linked Nanostructures

Achieving precise control over the morphology and function of polymeric nanostructures during self‐assembly remains a challenge in materials as well as biomedical science, especially when independent control over particle properties is desired. Herein, we report on nanostructures derived from amphiphilic block copolypept(o)ides by secondary‐structure‐directed self‐assembly, presenting a strategy to adjust core polarity and function separately from particle preparation in a bioreversible manner. The peptide‐inherent process of secondary‐structure formation allows for the synthesis of spherical and worm‐like core‐cross‐linked architectures from the same block copolymer, introducing a simple yet powerful approach to versatile peptide‐based core–shell nanostructures.     

Nanostructure control in polymer solar cells by self‐organization

Recently, polymer solar cells (PSCs) based on “bulk heterojunctions” using a simple mixture of electron donor and acceptor materials in thin films have been extensively studied. Although relatively high power conversion efficiencies have been achieved by using this approach, further improvement is necessary to precisely construct stable, reproducible nanostructures that are suitable for both efficient charge separation and transport inside such films. For this purpose, it is highly desirable to utilize a bottom‐up approach, such as the self‐organized formation of inorganic and organic nanostructures. In this review, an overview of our recent studies on the control of nanostructures in PSCs is presented. DOI 10.1002/tcr.201000015     

Engineering the Ionic Self‐Assembly of Polyoxometalates and Facial‐Like Peptides

The self‐assembly behavior of polyoxometalates (PMs) and facial‐like cationic peptides carrying lysine residues were systematically investigated. Circular dichroism and UV/Vis spectra demonstrated that the multivalent electrostatic attractions between polyanionic PMs and short peptides with protonated lysine residues initiated the conformational transition of peptide molecules from random‐coil to β‐sheet state, and subsequently the co‐assembly. TEM and atomic force microscopy (AFM) measurements showed that uniform nanofibers formed with decreasing size of the PMs or increasing the intermolecular forces of the peptides, such as through hydrogen‐bonding, hydrophobic, and/or π–π interactions. Additionally, the stability of the nanostructures can be improved by rational suppression of the electrostatic repulsion of the shell peptides covering the surface of the nanostructures. These results provide new insight into understanding the ionic self‐assembly of peptides and PMs and controlling their final morphology.     

Direct Synthesis of a Covalently Self‐Assembled Peptide Nanogel from a Tyrosine‐Rich Peptide Monomer and Its Biomineralized Hybrids

There has been significant progress in the self‐assembly of biological materials, but the one‐step covalent peptide self‐assembly for well‐defined nanostructures is still in its infancy. Inspired by the biological functions of tyrosine, a covalently assembled fluorescent peptide nanogel is developed by a ruthenium‐mediated, one‐step photo‐crosslinking of tyrosine‐rich short peptides under the visible light within 6 minutes. The covalently assembled peptide nanogel is stable in various organic solvents and different pH levels, unlike those made from vulnerable non‐covalent assemblies. The semipermeable peptide nanogel with a high density of redox‐active tyrosine acts as a novel nano‐bioreactor, allowing the formation of uniform metal–peptide hybrids by selective biomineralization under UV irradiation. As such, this peptide nanogel could be useful in the design of novel nanohybrids and peptidosomes possessing functional nanomaterials.     

Peptide‐poly(2‐(dimethylamino)ethyl methacrylate) conjugates: Synthesis and aqueous/nonaqueous self‐aggregation into nanostructures of dendritic and spherical morphologies

Peptide–polymer conjugate consisting of a sequence‐defined tripeptide and poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA) is synthesized by a simple “grafting from” atom transfer radical polymerization (ATRP) approach. The ATRP of PDMAEMA using peptide‐macroinitiator and CuBr/1,1,4,7,10,10‐hexamethyltriethylenetetramine system in anisole follows pseudo first order kinetics up to a conversion of about 25% within a time span of 125 min. The attachment of peptide moiety at the end of PDMAEMA chain is confirmed from MALDI‐TOF‐MS and circular dichroism analyses. The self‐assembly of as‐synthesized peptide‐PDMAEMA conjugate in organic solvents leads to the formation of spherical nanoparticles as observed through FESEM. Peptide‐PDMAEMA conjugate become soluble in water due to the protonation of the pendent —N(CH₃)₂ moiety of DMAEMA group of the conjugate. Owing to the amphiphilic nature of the protonated conjugate (peptide‐PDMAEMAH), it also undergoes self‐aggregation in water into nanostructures of various morphologies such as dendrite, small sphere and large sphere at pHs of 2, 8, and 10, respectively. Peptide‐PDMAEMA‐IBu conjugate obtained by the post‐modification of —N(CH₃)₂ moiety of DMAEMA group of the conjugate with n‐butylbromide also undergoes self‐aggregation into dendritic nanostructures in water. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3286–3297     

Peptides as New Smart Bionanomaterials: Molecular‐Recognition and Self‐Assembly Capabilities

Biomolecules express exquisite properties that are required for molecular recognition and self‐assembly on the nanoscale. These smart capabilities have developed through evolution and such biomolecules operate based on smart functions in natural systems. Recently, these remarkable smart capabilities have been utilized in not only biologically related fields, but also in materials science and engineering. A peptide‐screening technology that uses phage‐display systems has been developed based on this natural smart evolution for the generation of new functional peptide bionanomaterials. We focused on peptides that specifically bound to synthetic polymers. These polymer‐binding peptides were screened by using a phage‐display peptide library to recognize nanostructures that were derived from polymeric structural features and were utilized for possible applications as new bionanomaterials. We also focused on self‐assembling peptides with β‐sheet structures that formed nanoscale, fibrous structures for applications in new bottom‐up nanomaterials. Moreover, nanofiber‐binding peptides were also screened to introduce the desired functionalities into nanofibers without the need for additional molecular design. Our approach to construct new bionanomaterials that employ peptides will open up excellent opportunities for the next generation of materials science and technology.     

Hierarchical Self‐Assembled Photo‐Responsive Tubisomes from a Cyclic Peptide‐Bridged Amphiphilic Block Copolymer

Typically, the morphologies of the self‐assembled nanostructures from block copolymers are limited to spherical micelles, wormlike micelles and vesicles. Now, a new generation of materials with unique shape and structures, cylindrical soft matter particles (tubisomes), are obtained from the hierarchical self‐assembly of cyclic peptide‐bridged amphiphilic diblock copolymers. The capacity of obtained photo‐responsive tubisomes as potential drug carriers is evaluated. The supramolecular tubisomes pave an alternative way for fabricating polymeric tubular structures, and will expand the toolbox for the rational design of functional hierarchical nanostructures.     

Sonication‐Induced Coiled Fibrous Architectures of Boc‐L‐Phe‐L‐Lys(Z)‐OMe

An ultra‐short peptide Boc‐L ‐Phe‐L ‐Lys(Z)‐OMe (Z=carbobenzyloxy) was shown to act as a highly efficient and versatile low molecular weight gelator (LMWG) for a variety of aliphatic and aromatic solvents under sonication. Remarkably, this simple dipeptide is not only able to form coiled fibres but also demonstrates self‐healing and thermal chiroptical switching behaviour. The formation of coiled assemblies was found to be influenced by the nature of the solvent and the presence of an additive. By exploiting these properties it was possible to modulate the macroscopic and microscopic properties of the organogels of this ultra‐short peptide, allowing the formation of highly ordered single‐domain networks of helical fibres with dimeric or alternatively fibre‐bundle morphology. The organogels were characterized by using FTIR, SEM, NMR and circular dichroism (CD) spectroscopy. Interestingly, CD experiments showed that the organogels of Boc‐L ‐Phe‐L ‐Lys(Z)‐OMe in aromatic solvents exhibit thermal chiroptical switching. This behaviour was hypothesized to stem from changes in the morphology of the gel accompanied by conformational transformation of the gelling agent. The fact that such a small peptide can demonstrate hierarchical assemblies and the possibility of controlling the self‐association is rather intriguing. The self‐healing ability, chiroptical switching and more importantly the formation of helical assemblies by Boc‐L ‐Phe‐L ‐Lys(Z)‐OMe under sonication, make this dipeptide an interesting example of the self‐assembly ability of ultra‐short peptides.     

Self‐assembly of a Sequence‐shuffled Short Peptide Amphiphile Triggered by Metal Ions into Terraced Nanodome‐like Structures

We highlight the structural diversity of strategically designed two short peptide amphiphiles (sPAs) and describe their structure–function relationship studies. The shuffling of two key amino acids, that is, tyrosine and phenylalanine, in a designed sPA lead to a pair of constitutional isomers. Such small and strategic alteration can bring a substantial change in the self‐assembling pattern. Inspired from the naturally occurring metallopeptides, bioactive transition‐metal ions were used for constructing the unusual nanostructures. Use of appropriate metal ions created bigger differences between the properties of these isomers and hence the self‐assembly. Coordination of appropriate transition metal ions modifies the internal nanoscale structures of sPA, thus leading to the formation of vertically stacked terraced layers with decreasing size, which possess a high degree of dimensional regularity. We propose that such metal‐induced terraced nanodome‐like hierarchical self‐assembly may have relevance for specific biotechnology applications.     

Hierarchical Self‐Assembly of Supramolecular Hydrophobic Metallacycles into Ordered Nanostructures

We describe herein the hierarchical self‐assembly of discrete supramolecular metallacycles into ordered fibers or spherical particles through multiple noncovalent interactions. A new series of well‐defined metallacycles decorated with long alkyl chains were obtained through metal–ligand interactions, which were capable of aggregating into ordered fibroid or spherical nanostructures on the surface, mostly driven by hydrophobic interactions. In‐depth studies indicated that the morphology diversity was originated from the structural information encoded in the metallacycles, including the number of alkyl chains and their spatial orientation. Interestingly, the morphology of the metallacycle aggregates could be tuned by changing the solvent polarity. These findings are of special significance since they provide a simple yet highly controllable approach to prepare ordered and tunable nanostructures from small building blocks by means of hierarchical self‐assembly.     

Hierarchical Analysis of Self‐Assembled PEGylated Hexaphenylalanine Photoluminescent Nanostructures

Despite the growing literature about diphenylalanine‐based peptide materials, it still remains a challenge to delineate the theoretical insight into peptide nanostructure formation and the structural features that could permit materials with enhanced properties to be engineered. Herein, we report the synthesis of a novel peptide building block composed of six phenylalanine residues and eight PEG units, PEG₈‐F6. This aromatic peptide self‐assembles in water in stable and well‐ordered nanostructures with optoelectronic properties. A variety of techniques, such as fluorescence, FTIR, CD, DLS, SEM, SAXS, and WAXS allowed us to correlate the photoluminescence properties of the self‐assembled nanostructures with the structural organization of the peptide building block at the micro‐ and nanoscale. Finally, a model of hexaphenylalanine in aqueous solution by molecular dynamics simulations is presented to suggest structural and energetic factors controlling the formation of nanostructures.     

A Molecular Dynamics Study on Controlling the Self‐Assembly of β‐Sheet Peptides with Designer Nanorings

Recently, a rational approach for constructing β‐barrel protein mimics by the self‐assembly of peptide‐based building blocks has been demonstrated. We performed molecular dynamics simulations of nanoring formation by means of the self‐assembly of designed β‐sheet‐forming peptides. Several factors contributing to the stability of the nanoring structures with respect to size were investigated. Our simulations predicted that an optimal nanoring size may be achieved by minimizing repulsions due to steric hindrance between bulky groups while maintaining favorable hydrogen‐bond interactions between neighboring β‐sheet chains. It was shown that mutations in a test peptide, in which all or half of the tryptophan residues were replaced by phenylalanine, could enable the assembly of stable nanoring structures with smaller pore sizes. Insights into the fundamental factors driving the formation of peptide‐based nanostructures are expected to facilitate the design of novel functional bionanostructures.     

Self‐Assembly of Wireframe DNA Nanostructures from Junction Motifs

Wireframe frameworks have been investigated for the construction of complex nanostructures from a scaffolded DNA origami approach; however, a similar framework is yet to be fully explored in a scaffold‐free “LEGO” approach. Herein, we describe a general design scheme to construct wireframe DNA nanostructures entirely from short synthetic strands. A typical edge of the resulting structures in this study is composed of two parallel duplexes with crossovers on both ends, and three, four, or five edges radiate out from a certain vertex. By using such a self‐assembly scheme, we produced planar lattices and polyhedral objects.     

Three‐Dimensional Ordered Antibody Arrays Through Self‐Assembly of Antibody–Polymer Conjugates

Three‐dimensional (3D) ordered arrays of human immunoglobulin G (IgG) were fabricated using well‐defined full‐length antibody–polymer conjugates (APCs). The conjugates were prepared through a two‐step sequential click approach with a combination of oxime ligation and strain promoted alkyne–azide cycloaddition. They were able to self‐assemble into lamellar nanostructures with alternating IgG and poly(N ‐isopropylacrylamide) (PNIPAM) nanodomains. As a proof‐of‐concept, these materials were fabricated into thin films and their specific binding ability was tested. The nanostructure not only improves the packing density and the proper orientation of the IgG, but also provides nanochannels to facilitate substrate transport.     

Biocatalytic Self‐Assembly of Supramolecular Charge‐Transfer Nanostructures Based on n‐Type Semiconductor‐Appended Peptides

The reversible in situ formation of a self‐assembly building block (naphthalenediimide (NDI)–dipeptide conjugate) by enzymatic condensation of NDI‐functionalized tyrosine ( NDI‐Y ) and phenylalanine‐amide ( F‐NH₂ ) to form NDI‐YF‐NH₂ is described. This coupled biocatalytic condensation/assembly approach is thermodynamically driven and gives rise to nanostructures with optimized supramolecular interactions as evidenced by substantial aggregation induced emission upon assembly. Furthermore, in the presence of di‐hydroxy/alkoxy naphthalene donors, efficient charge‐transfer complexes are produced. The dynamic formation of NDI‐YF‐NH₂ and electronic and H‐bonding interactions are analyzed and characterized by different methods. Microscopy (TEM and AFM) and rheology are used to characterize the formed nanostructures. Dynamic nanostructures, whose formation and function are driven by free‐energy minimization, are inherently self‐healing and provide opportunities for the development of aqueous adaptive nanotechnology.     

Regulating Higher‐Order Organization through the Synergy of Two Self‐Sorted Assemblies

The extracellular matrix (ECM) is the natural fibrous scaffold that regulates cell behavior in a hierarchical manner. By mimicking the dynamic and reciprocal interactions between ECM and cells, higher‐order molecular self‐assembly (SA), mediated through the dynamic growth of scaffold‐like nanostructures assembled by different molecular components, was developed. Designed and synthesized were two self‐sorted coumarin‐based gelators, a peptide molecule and a benzoate molecule, which self‐assemble into nanofibers and nanobelts, respectively, with different dynamic profiles. Upon the dynamic growth of the fibrous scaffold assembled from peptide gelators, nanobelts assembled from benzoate gelators transform into a layer‐by‐layer nanosheet, reaching ninefold increase in height. By using light and an enzyme, the spatial–temporal growth of the scaffold can be modified, leading to in situ height regulation of the higher‐order architecture.     

A Signal‐Passing DNA‐Strand‐Exchange Mechanism for Active Self‐Assembly of DNA Nanostructures

DNA nanostructured tiles play an active role in their own self‐assembly in the system described herein whereby they initiate a binding event that produces a cascading assembly process. We present DNA tiles that have a simple but powerful property: they respond to a binding event at one end of the tile by passing a signal across the tile to activate a binding site at the other end. This action allows sequential, virtually irreversible self‐assembly of tiles and enables local communication during the self‐assembly process. This localized signal‐passing mechanism provides a new element of control for autonomous self‐assembly of DNA nanostructures.     

Facile Synthesis of Three‐Dimensional Pt‐TiO2 Nano‐networks: A Highly Active Catalyst for the Hydrolytic Dehydrogenation of Ammonia–Borane

Three‐dimensional (3D) porous metal and metal oxide nanostructures have received considerable interest because organization of inorganic materials into 3D nanomaterials holds extraordinary properties such as low density, high porosity, and high surface area. Supramolecular self‐assembled peptide nanostructures were exploited as an organic template for catalytic 3D Pt‐TiO₂ nano‐network fabrication. A 3D peptide nanofiber aerogel was conformally coated with TiO₂ by atomic layer deposition (ALD) with angstrom‐level thickness precision. The 3D peptide‐TiO₂ nano‐network was further decorated with highly monodisperse Pt nanoparticles by using ozone‐assisted ALD. The 3D TiO₂ nano‐network decorated with Pt nanoparticles shows superior catalytic activity in hydrolysis of ammonia–borane, generating three equivalents of H₂.     

Rational Design of Nanofibers and Nanorings through Complementary Hydrogen‐Bonding Interactions of Functional π Systems

A simple protocol to create nanofibers and ‐rings through a rational self‐assembly approach is described. Whereas the melamine–oligo(p‐phenylenevinylene) conjugate 1 a self‐aggregates to form ill‐defined nanostructures, conjugate 1 b , which possesses an amide group as an additional interactive site, self‐aggregates to form 1D nanofibers that induce gelation of the solvent. AFM and XRD studies have shown that dimerization through the melamine–melamine hydrogen‐bonding interaction occurs only for 1 b . Upon complexation with 1/3 equivalents of cyanuric acid (CA), conjugate 1 a provides well‐defined, ring‐shaped nanostructures at micromolar concentrations, which open to form fibrous assemblies at submillimolar concentrations and organogels in the millimolar concentration range. Apparently, the enhanced aggregation ability of 1 a by CA is a consequence of columnar organization of the resulting discotic complex 1 a ₃ ? CA. In contrast, coaggregation of 1 b with CA does not provide well‐defined nanostructures, probably due to the interference of complementary hydrogen‐bonding interactions by the amide group.     

Thio‐Bromo “Click” Reaction Derived Polymer–Peptide Conjugates for Their Self‐Assembled Fibrillar Nanostructures

The synthesis and self‐assembly of peptide–polymer conjugates into fibrillar nanostructures are reported, based on the amyloidogenic peptide KLVFF. A strategy for rational synthesis of polymer–peptide conjugates is documented via tethering of the amyloidogenic peptide segment LVFF (Aβ_17‐20) and its modified derivative FFFF to the hydrophilic poly(ethylene glycol) monomethyl ether (mPEG) polymer via thio‐bromo based “click” chemistry. The resultant conjugates mPEG‐LVFF‐OMe and mPEG‐FFFF‐OMe are purified via preparative gel permeation chromatography technique (with a yield of 61% and 64%, respectively), and are successfully characterized via combination of spectroscopic and chromatographic methods, including electrospray ionization time‐of‐flight mass spectrometry. The peptide‐guided self‐assembling behavior of the as‐constructed amphiphilic supramolecular materials is further investigated via transmission electron microscopic and circular dichroism spectroscopic analysis, exhibiting fibrillar nanostructure formation in binary aqueous solution mixture.