Drug Conjugation to Cyclic Peptide–Polymer Self‐Assembling Nanotubes

We show for the first time how polymeric nanotubes (NTs) based on self‐assembled conjugates of polymers and cyclic peptides can be used as an efficient drug carrier. RAPTA‐C, a ruthenium‐based anticancer drug, was conjugated to a statistical co‐polymer based on poly(2‐hydroxyethyl acrylate) (pHEA) and poly(2‐chloroethyl methacrylate) (pCEMA), which formed the shell of the NTs. Self‐assembly into nanotubes (length 200–500 nm) led to structures exhibiting high activity against cancer cells.     

Tunable Self‐Assembly of Triazole‐Linked Porphyrin–Polymer Conjugates

The convergence of supramolecular chemistry and polymer science offers many powerful approaches for building functional nanostructures with well‐defined dynamic behaviour. Herein we report the efficient “click” synthesis and self‐assembly of AB₂‐ and AB₄‐type multitopic porphyrin–polymer conjugates (PPCs). PPCs were prepared using the copper(I)‐catalysed azide–alkyne cycloaddition (CuAAC) reaction, and consisted of linear polystyrene, poly(butyl acrylate), or poly(tert‐butyl acrylate) arms attached to a zinc(II) porphyrin core via triazole linkages. We exploit the presence of the triazole groups obtained from CuAAC coupling to direct the self‐assembly of the PPCs into short oligomers (2–6 units in length) via intermolecular porphyrinatozinc–triazole coordination. By altering the length and grafting density of the polymer arms, we demonstrate that the association constant of the porphyrinatozinc–triazole complex can be systematically tuned over two orders of magnitude. Self‐assembly of the PPCs also resulted in a 6 K increase in the glass transition temperature of the bulk material compared to a non‐assembling PPC. The modular synthesis and tunable self‐assembly of the triazole‐linked PPCs thus represents a powerful supramolecular platform for building functional nanostructured materials.     

Hydrophobic Self‐Assembly Affords Robust Noncovalent Polymer Isomers

In covalent polymerization, a single monomer can result in different polymer structures due to positional, geometric, or stereoisomerism. We demonstrate that strong hydrophobic interactions result in stable noncovalent polymer isomers that are based on the same covalent unit (amphiphilic perylene diimide). These isomers have different structures and electronic/photonic properties, and are stable in water, even upon prolonged heating at 100 °C. Such combination of covalent‐like stability together with structural/functional variation is unique for noncovalent polymers, substantially advancing their potential as functional materials.     

Controllable Peptide–Dendron Self‐Assembly: Interconversion of Nanotubes and Fibrillar Nanostructures

Roll up : A peptide–dendron hybrid (PDH) is capable of self‐assembling into either a soluble nanotube or an amyloid‐like fibrillar network. The structures interconvert on adjusting the salt concentration or pH value. Their hydrophobic interfaces efficiently encapsulate hydrophobic molecules in water which can then be released by lowering the pH value.

     

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.     

Multicomponent Supramolecular Systems: Self‐Organization in Coordination‐Driven Self‐Assembly

The self‐organization of multicomponent supramolecular systems involving a variety of two‐dimensional (2 D) polygons and three‐dimensional (3 D) cages is presented. Nine self‐organizing systems, SS₁ – SS₉ , have been studied. Each involves the simultaneous mixing of organoplatinum acceptors and pyridyl donors of varying geometry and their selective self‐assembly into three to four specific 2 D (rectangular, triangular, and rhomboid) and/or 3 D (triangular prism and distorted and nondistorted trigonal bipyramidal) supramolecules. The formation of these discrete structures is characterized using NMR spectroscopy and electrospray ionization mass spectrometry (ESI‐MS). In all cases, the self‐organization process is directed by: 1) the geometric information encoded within the molecular subunits and 2) a thermodynamically driven dynamic self‐correction process. The result is the selective self‐assembly of multiple discrete products from a randomly formed complex. The influence of key experimental variables ‐ temperature and solvent ‐ on the self‐correction process and the fidelity of the resulting self‐organization systems is also described.     

Study of (Cyclic Peptide)–Polymer Conjugate Assemblies by Small‐Angle Neutron Scattering

We present a fundamental study into the self‐assembly of (cyclic peptide)–polymer conjugates as a versatile supramolecular motif to engineer nanotubes with defined structure and dimensions, as characterised in solution using small‐angle neutron scattering (SANS). This work demonstrates the ability of the grafted polymer to stabilise and/or promote the formation of unaggregated nanotubes by the direct comparison to the unconjugated cyclic peptide precursor. This ideal case permitted a further study into the growth mechanism of self‐assembling cyclic peptides, allowing an estimation of the cooperativity. Furthermore, we show the dependency of the nanostructure on the polymer and peptide chemical functionality in solvent mixtures that vary in the ability to compete with the intermolecular associations between cyclic peptides and ability to solvate the polymer shell.     

Fluorescent Cross‐Linked Supramolecular Polymer Constructed by Orthogonal Self‐Assembly of Metal–Ligand Coordination and Host–Guest Interaction

A new host molecule consists of four terpyridine groups as the binding sites with zinc(II) ion and a copillar[5]arene incorporated in the center as a spacer to interact with guest molecule was designed and synthesized. Due to the 120 ° angle of the rigid aromatic segment, a cross‐linked dimeric hexagonal supramolecular polymer was therefore generated as the result of the orthogonal self‐assembly of metal–ligand coordination and host–guest interaction. UV/Vis spectroscopy, ¹H NMR spectroscopy, viscosity and dynamic light‐scattering techniques were employed to characterize and understand the cross‐linking process with the introduction of zinc(II) ion and guest molecule. More importantly, well‐defined morphology of the self‐assembled supramolecular structure can be tuned by altering the adding sequence of the two components, that is, the zinc(II) ion and the guest molecule. In addition, introduction of a competitive ligand suggested the dynamic nature of the supramolecular structure.     

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.     

Synthesis and Supramolecular Self‐Assembly of Coil‐Rod‐Coil Molecules: The Relationship between Self‐Assembled Nanostructures and Molecular Structures

Herein, the relationship between the supramolecularly self‐assembled nanostructures and the chemical structures of coil‐rod‐coil molecules is discussed. A series of nonamphiphilic coil‐rod‐coil molecules with different alkyl chains, central mesogenic groups, and chemical linkers were designed and synthesized. The solvent‐mediated supramolecular self‐assembling of these coil‐rod‐coil molecules resulted in rolled‐up nanotubes, nanofibers, submicron sized belts, needle‐like microcrystals, and amorphous structures. The self‐assembling behaviors of these coil‐rod‐coil molecules have been systematically investigated to reveal the relationship between the supramolecularly self‐assembled nanostructures and their chemical structures. With respect to the formation of rolled‐up nanotubes by self‐assembly of coil‐rod‐coil molecules, we have systematically investigated the following three influencing structural factors: 1) the alkyl chain length; 2) the central mesogenic group; (3) the linker type. These studies disclosed the key structural features of coil‐rod‐coil molecules for the formation of rolled‐up nanotubes.     

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.     

Toughening a Self‐Healable Supramolecular Polymer by Ionic Cluster‐Enhanced Iron‐Carboxylate Complexes

Supramolecular polymers that can heal themselves automatically usually exhibit weakness in mechanical toughness and stretchability. Here we exploit a toughening strategy for a dynamic dry supramolecular network by introducing ionic cluster‐enhanced iron‐carboxylate complexes. The resulting dry supramolecular network simultaneous exhibits tough mechanical strength, high stretchability, self‐healing ability, and processability at room temperature. The excellent performance of these distinct supramolecular polymers is attributed to the hierarchical existence of four types of dynamic combinations in the high‐density dry network, including dynamic covalent disulfide bonds, noncovalent H‐bonds, iron‐carboxylate complexes and ionic clustering interactions. The extremely facile preparation method of this self‐healing polymer offers prospects for high‐performance low‐cost material among others for coatings and wearable devices.     

Synthesis and Self‐Assembly of Cyclic 2,7‐Anthrylene Ethynylene 1,3‐Phenylene Ethynylene Trimer with a Planar Conformation

Cyclic arylene ethynylene hexamer 1 , composed of alternating 2,7‐anthrylene ethynylene units and meta‐phenylene ethynylene units, was synthesized. It shows C₃ symmetry and possesses a flat and rigid conformation with a large equilateral triangle‐like cavity. Macrocycle 1 self‐associates through π–π stacking interactions between the anthracene‐containing macrocyclic aromatic cores with indefinite‐association constant K_E=6980 m ^?1 in CDCl₃ at 303 K. Macrocycle 1 also self‐assembles into π‐stacked nanofibers in the drop‐cast film.     

A Multiple Multicomponent Approach to Chimeric Peptide–Peptoid Podands

The success of multi‐armed, peptide‐based receptors in supramolecular chemistry traditionally is not only based on the sequence but equally on an appropriate positioning of various peptidic chains to create a multivalent array of binding elements. As a faster, more versatile and alternative access toward (pseudo)peptidic receptors, a new approach based on multiple Ugi four‐component reactions (Ugi‐4CR) is proposed as a means of simultaneously incorporating several binding and catalytic elements into organizing scaffolds. By employing α‐amino acids either as the amino or acid components of the Ugi‐4CRs, this multiple multicomponent process allows for the one‐pot assembly of podands bearing chimeric peptide–peptoid chains as appended arms. Tripodal, bowl‐shaped, and concave polyfunctional skeletons are employed as topologically varied platforms for positioning the multiple peptidic chains formed by Ugi‐4CRs. In a similar approach, steroidal building blocks with several axially‐oriented isocyano groups are synthesized and utilized to align the chimeric chains with conformational constrains, thus providing an alternative to the classical peptido‐steroidal receptors. The branched and hybrid peptide–peptoid appendages allow new possibilities for both rational design and combinatorial production of synthetic receptors. The concept is also expandable to other multicomponent reactions.     

Supramolecular Polymer Network‐Mediated Self‐Assembly of Semicrystalline Polymers with Excellent Crystalline Performance

A novel application of supramolecular interactions within semicrystalline polymers, capable of self‐assembling into supramolecular polymer networks via self‐complementary multiple hydrogen‐bonded complexes, is demonstrated for efficient construction of highly controlled self‐organizing hierarchical structures to offer a direct, efficient nucleation pathway resulting in superior crystallization performance. Herein, a novel functionalized poly(ε‐caprolactone) containing self‐complementary sextuple hydrogen‐bonded uracil‐diamidopyridine (U‐DPy) moieties is successfully developed and demonstrated excellent thermal and viscoelastic properties as well as high dynamic structural stability in the bulk state due to physical cross‐linking created by reversible sextuple hydrogen bonding between U‐DPy units. Due to the ability to vary the extent of the reversible network by tuning the U‐DPy content, this newly developed material can be readily adjusted to obtain the desired crystalline products with specific characteristics. Importantly, incorporating only 0.1% U‐DPy resulted in a polymer with a high crystallization rate constant, short crystallization half‐time, and much more rapid crystallization kinetics than pristine PCL, indicating a low content of U‐DPy moieties provides highly efficient nucleation sites that manipulate the nucleation and growth processes of polymer crystals to promote crystallization and chain alignment in bulk. This new system is suggested as a potential new route to substantially improve the performance of polymer crystallization.

     

Emergent Catalytic Behavior of Self‐Assembled Low Molecular Weight Peptide‐Based Aggregates and Hydrogels

We report a series of short peptides possessing the sequence (FE)_n or (EF)_n and bearing l ‐proline at their N‐terminus that self‐assemble into high aspect ratio aggregates and hydrogels. We show that these aggregates are able to catalyze the aldol reaction, whereas non‐aggregated analogues are catalytically inactive. We have undertaken an analysis of the results, considering the accessibility of catalytic sites, pK_a value shifts, and the presence of hydrophobic pockets. We conclude that the presence of hydrophobic regions is indeed relevant for substrate solubilization, but that the active site accessibility is the key factor for the observed differences in reaction rates. The results presented here provide an example of the emergence of a new chemical property caused by self‐assembly, and support the relevant role played by self‐assembled peptides in prebiotic scenarios. In this sense, the reported systems can be seen as primitive aldolase I mimics, and have been successfully tested for the synthesis of simple carbohydrate precursors.