Temperature‐induced self‐assembly and metal‐ion stabilization of histidine functional block copolymers

Histidine functional block copolymers are thermally self‐assembled into polymer micelles with poly‐N‐isopropylacrylamide in the core and the histidine functionality in the corona. The thermally induced self‐assemblies are reversible until treated with Cu²⁺ ions at 50 °C. Upon treatment with 0.5 equivalents of Cu²⁺ relative to the histidine moieties, metal‐ion coordination locks the self‐assemblies. The self‐assembly behavior of histidine functional block copolymers is explored at different values of pH using DLS and ¹H NMR. Metal‐ion coordination locking of the histidine functional micelles is also explored at different pH values, with stable micelles forming at pH 9, observed by DLS and imaged by atomic force microscopy. The thermal self‐assembly of glycine functional block copolymers at pH 5, 7, and 9 is similar to the histidine functional materials; however, the self‐assemblies do not become stable after the addition of Cu²⁺, indicating that the imidazole plays a crucial role in metal‐ion coordination that locks the micelles. The reversibility of the histidine‐copper complex locking mechanism is demonstrated by the addition of acid to protonate the imidazole and destabilize the polymer self‐assemblies. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1964–1973     

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.     

Self‐Assembly of Coiled Coils in Synthetic Biology: Inspiration and Progress

Biological self‐assembly is very complex and results in highly functional materials. In effect, it takes a bottom‐up approach using biomolecular building blocks of precisely defined shape, size, hydrophobicity, and spatial distribution of functionality. Inspired by, and drawing lessons from self‐assembly processes in nature, scientists are learning how to control the balance of many small forces to increase the complexity and functionality of self‐assembled nanomaterials. The coiled‐coil motif, a multipurpose building block commonly found in nature, has great potential in synthetic biology. In this review we examine the roles that the coiled‐coil peptide motif plays in self‐assembly in nature, and then summarize the advances that this has inspired in the creation of functional units, assemblies, and systems.     

Hyper‐Assembly of Self‐Assembled Glycoclusters Mediated by Specific Carbohydrate–Carbohydrate Interactions

Hybridization of a self‐assembled, spherical complex with oligosaccharides containing Lewis X, a functional trisaccharide displayed on various cell surfaces, yielded well‐defined glycoclusters. The self‐assembled glycoclusters exhibited homophilic hyper‐assembly in aqueous solution in a Ca²⁺‐dependent manner through specific carbohydrate–carbohydrate interactions, offering a structural scaffold for functional biomimetic systems.     

Oligopeptide‐Assisted Self‐Assembly of Oligothiophenes: Co‐Assembly and Chirality Transfer

The biomolecule‐assisted self‐assembly of semiconductive molecules has been developed recently for the formation of potential bio‐based functional materials. Oligopeptide‐assisted self‐assembly of oligothiophene through weak intermolecular interactions was investigated; specifically the self‐assembly and chirality‐transfer behavior of achiral oligothiophenes in the presence of an oligopeptide with a strong tendency to form β‐sheets. Two kinds of oligothiophenes without (QT) or with (QTDA) carboxylic groups were selected to explore the effect of the end functional group on self‐assembly and chirality transfer. In both cases, organogels were formed. However, the assembly behavior of QT was quite different from that of QTDA. It was found that QT formed an organogel with the oligopeptide and co‐assembled into chiral nanostructures. Conversely, although QTDA also formed a gel with the oligopeptide, it has a strong tendency to self‐assemble independently. However, during the formation of the xerogel, the chirality of the oligopeptide can also be transferred to the QTDA assemblies. Different assembly models were proposed to explain the assembly behavior.     

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.     

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.     

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.     

Self‐Assembly through Coordination and π‐Stacking: Controlled Switching of Circularly Polarized Luminescence

Multiple noncovalent interactions can drive self‐assembly through different pathways. Here, by coordination‐assisted changes in π‐stacking modes between chromophores in pyrene‐conjugated histidine (PyHis), a self‐assembly system with reversible and inversed switching of supramolecular chirality, as well as circularly polarized luminescence (CPL) is described. It was found that l ‐PyHis self‐assembled into nanofibers showing P‐chirality and right‐handed CPL. Upon Zn^II coordination, the nanofibers changed into nanospheres with M‐chirality, as well as left‐handed CPL. The process is reversible and the M‐chirality can change to P‐chirality by removing the Zn^II ions. Experimental and theoretical models unequivocally revealed that the cooperation of metal coordination and π‐stacking modes are responsible the reversible switching of supramolecular chirality. This work not only provides insight into how multiple noncovalent interactions regulate self‐assembly pathways.     

Co‐assembly of Patchy Polymeric Micelles and Protein Molecules

The development in the synthesis and self‐assembly of patchy nanoparticles has resulted in the creation of complex hierarchical structures. Co‐assembly of polymeric nanoparticles and protein molecules combines the advantages of polymeric materials and biomolecules, and will produce new functional materials. Co‐assembly of positively charged patchy micelles and negatively charged bovine serum albumin (BSA) molecules is investigated. The patchy micelles, which were synthesized using block copolymer brushes as templates, leads to co‐assembly with protein molecules into vesicular structures. The average size of the assembled structures can be controlled by the molar ratio of BSA to patchy micelles. The assembled structures are dissociated in the presence of trypsin. The protein–polymer hybrid vesicles could find potential applications in medicine.     

Redox‐Active Peptide‐Functionalized Quinquethiophene‐Based Electrochromic π‐Gel

An electrochromic system based on a self‐assembled dipeptide‐appended redox‐active quinquethiophene π‐gel is reported. The designed peptide‐quinquethiophene consists of a symmetric bolaamphiphile that has two segments: a redox‐active π‐conjugated quinquethiophene core for electrochromism, and peptide motif for the involvement of molecular self‐assembly. Investigations reveal that self‐assembly and electrochromic properties of the π‐gel are strongly dependent on the relative orientation of peptidic and quinquethiophene scaffolds in the self‐assembly system. The colors of the π‐gel film are very stable with fast and controlled switching speed at room temperature.     

Carbonic Anhydrase‐Mimetic Bolaamphiphile Self‐Assembly for CO2 Hydration and Sequestration

A biomimetic catalyst was prepared through the self‐assembly of a bolaamphiphilic molecule with histidine moieties for the sequestration of carbon dioxide. The histidyl bolaamphiphilic molecule bis(N‐α‐amidohistidine)‐1,7‐heptane dicarboxylate has been synthesized and self‐assembled to produce analogues of the active sites of carbonic anhydrase (CA) after association with Zn²⁺ ions. Spectroscopic analysis demonstrated the coordination of the Zn²⁺ ions with histidine imidazole moieties, which is the core conformation of CA active sites. The Zn‐associated self‐assembly worked as a CA‐mimetic catalyst that shows catalytic activity for CO₂ hydration. Evaluation of the kinetics of using para‐nitrophenylacetate revealed that the kinetic parameters of the CA‐mimetic catalyst were maximized at the optimal Zn concentration and that excess Zn ions resulted in deteriorated catalytic activity. The performance of the CA‐mimetic catalyst was enhanced by changing the pH value and temperature of the reaction, which implies that the hydrolysis of the substrate is the rate‐determining step. The catalyst‐assisted sequestration of CO₂ was demonstrated by CaCO₃ precipitation upon the addition of Ca²⁺ ions. This study offers an easy way to prepare enzyme analogues for CO₂ sequestration through the self‐assembly of bolaamphiphile molecules with designer biochemical moieties.     

Engineering Multifunctional DNA Hybrid Nanospheres through Coordination‐Driven Self‐Assembly

Developing simple and general approaches for the synthesis of nanometer‐sized DNA materials with specific morphologies and functionalities is important for various applications. Herein, a novel approach for the synthesis of a new set of DNA‐based nanoarchitectures through coordination‐driven self‐assembly of Fe^II ions and DNA molecules is reported. By fine‐tuning the assembly, Fe–DNA nanospheres of precise sizes and controlled compositions can be produced. The hybrid nanoparticles can be tailored for delivery of functional DNA to cells in vitro and in vivo with enhanced biological function. This highlights the potential of metal ion coordination as a tool for directing the assembly of DNA architectures, which conceptualizes a new pathway to expand the repertoire of DNA‐based nanomaterials. This methodology will advance both the fields of DNA nanobiotechnology and metal–ligand coordination chemistry.     

Ion‐Selective Electrodes Based on Hydrophilic Ionophore‐Modified Nanopores

We report the synthesis and analytical application of the first Cu²⁺‐selective synthetic ion channel based on peptide‐modified gold nanopores. A Cu²⁺‐binding peptide motif (Gly‐Gly‐His) along with two additional functional thiol derivatives inferring cation‐permselectivity and hydrophobicity was self‐assembled on the surface of gold nanoporous membranes comprising of about 5 nm diameter pores. These membranes were used to construct ion‐selective electrodes (ISEs) with extraordinary Cu²⁺ selectivities, approaching six orders of magnitude over certain ions. Since all constituents are immobilized to a supporting nanoporous membrane, their leaching, that is a ubiquitous problem of conventional ionophore‐based ISEs was effectively suppressed.     

Pulsed Laser‐Driven Molecular Self‐assembly of Cephalexin: Aggregation‐Induced Fluorescence and Its Utility as a Mercury Ion Sensor

A fluorescent self‐assembly of cephalexin is obtained by pulsed laser irradiation process. An intense fluorescence emission is found in the self‐assembled form due to occurrence of a typical aggregation‐induced emission in cephalexin molecules. It is observed that fluorescence quenching of the self‐assembled fluorescent nanostructures occurs in the presence of extremely low Hg⁺⁺ ions concentrations (10^?7 m ) as compared to other heavy metal ions e.g. Ferrous (Fe⁺⁺), Manganese (Mn⁺⁺), Magnesium (Mg⁺⁺), Cobalt (Co⁺⁺), Nickel (Ni⁺⁺) and Zinc (Zn⁺⁺) at the same concentrations.     

Reversible Self‐Assembly of Carboxylated Peptide‐Functionalized Gold Nanoparticles Driven by Metal‐Ion Coordination

Carboxylated peptide‐functionalized gold nanoparticles (peptide‐GNPs) self‐assemble into two‐ and three‐dimensional nanostructures in the presence of various heavy metal ions (i.e. Pb²⁺, Cd²⁺, Cu²⁺, and Zn²⁺) in aqueous solution. The assembly process is monitored by following the changes in the surface plasmon resonance (SPR) band of gold nanoparticles in a UV/Vis spectrophotometer, which shows the development of a new SPR band in the higher‐wavelength region. The extent of assembly is dependent on the amount of metal ions present in the medium and also the time of assembly. TEM analysis clearly shows formation of two‐ and three‐dimensional nanostructures. The assembly process is completely reversible by addition of alkaline ethylenediaminetetraacetic acid (EDTA) solution. The driving force for the assembly of peptide‐GNPs is mainly metal ion/carboxylate coordination. The color and spectral changes due to this assembly can be used for detection of these heavy‐metal ions in solution.     

An “Ingredients” Approach to Functional Self‐Synthesizing Materials: A Metal‐Ion‐Selective,Multi‐Responsive,Self‐Assembled Hydrogel

New methodology for making novel materials is highly desirable. Here, an “ingredients” approach to functional self‐assembled hydrogels was developed. By designing a building block to contain the right ingredients, a multi‐responsive, self‐assembled hydrogel was obtained through a process of template‐induced self‐synthesis in a dynamic combinatorial library. The system can be switched between gel and solution by light, redox reactions, pH, temperature, mechanical energy and sequestration or addition of Mg^II salt.     

Metal–Organic Gels from Silver Nanoclusters with Aggregation‐Induced Emission and Fluorescence‐to‐Phosphorescence Switching

Luminescent metal nanoclusters (NCs) are emerging as a new class of functional materials that have rich physicochemical properties and wide potential applications. In recent years, it has been found that some metal NCs undergo aggregation‐induced emission (AIE) and an interesting fluorescence‐to‐phosphorescence (F‐P) switching in solutions. However, insights of both the AIE and the F‐P switching remain largely unknown. Now, gelation of water soluble, atomically precise Ag₉ NCs is achieved by the addition of antisolvent. Self‐assembly of Ag₉ NCs into entangled fibers was confirmed, during which AIE was observed together with an F‐P switching occurring within a narrow time scale. Structural evaluation indicates the fibers are highly ordered. The self‐assembly of Ag₉ NCs and their photoluminescent property are thermally reversible, making the metal–organic gels good candidates for luminescent ratiometric thermometers.     

Mimicking Primitive Photobacteria: Sustainable Hydrogen Evolution Based on Peptide–Porphyrin Co‐Assemblies with a Self‐Mineralized Reaction Center

Molecular evolution, with self‐organization of simple molecules towards complex functional systems, provides a new strategy for biomimetic architectonics and perspectives for understanding the complex processes of life. However, there remain many challenges to fabrication of systems comprising different types of units, which interact with one another to perform desired functions. Challenges arise from a lack of stability, dynamic properties, and functionalities that reconcile with a given environment. A co‐assembling fiber system composed of simple peptide and porphyrin is presented. This material is considered a prebiotic assembly of molecules that can be rather stable and flexibly self‐functionalized with the assistance of visible light in a “prebiotic soup”; acidic (pH 2), hot (70 °C), and mineral‐containing (Na⁺, Ti⁴⁺, Pt²⁺, and so forth) water. The co‐assembled peptide–porphyrin fiber, with self‐mineralized reaction centers, may serve as a primitive photobacteria‐like cellular model to achieve light harvesting, energy transfer, and ultimately sustainable hydrogen evolution.     

Self‐Assembly of Bolaamphiphilic Molecules

The current buzzword in science and technology is self‐assembly and molecular self‐assembly is one of the most prominent fields as far as research in chemical and biological sciences is concerned. Generally, self‐assembly of molecules occurs through weak non‐covalent interactions like hydrogen bonding, π–π stacking, hydrophobic effects, etc. Inspired by many natural systems consisting of self‐assembled structures, scientists have been trying to understand their formation and mimic such processes in the laboratory to create functional “smart” materials, which respond to temperature, light, pH, electromagnetic field, mechanical stress, and/or chemical stimuli. These responses are usually manifested as remarkable changes from the molecular (e. g., conformational state, hierarchical order) to the macroscopic level (e. g., shape, surface properties). Many molecules such as peptides, viruses, and surfactants are known to self‐assemble into different structures. Among them, glycolipids are the new entries in the area of molecules that are being investigated for their self‐assembly characteristics. Among the different classes of glycolipids like rhamnolipids and trehalose lipids, owing to their biological preparations and their structural novelty, sophorolipids (SLs) are evoking greater interest among researchers. Sophorolipids are a class of asymmetric bolas bearing COOH groups at one end and sophorose (dimeric glucose linked by an unusual β(1→2) linkage). The extreme membrane stability of Archaea, attributed to the membrane‐spanning bolas (tetraether glycolipids), has inspired chemists to unravel the molecular designs that underpin the self‐assembly of bolaamphiphilic molecules. Apart from these self‐assembled structures, bolaamphiphiles find applications in many fields such as drug delivery, membrane mimicking, siRNA therapies, etc. The first part of this Personal Account presents some possible self‐assembled structures of bolaamphiphiles and their mechanism of formation. The later part covers our work on one of the typical bolaamphiphiles known as sophorolipids.