Self‐Assembly of α‐Helical Polypeptides Driven by Complex Coacervation

Reported is the ability of α‐helical polypeptides to self‐assemble with oppositely‐charged polypeptides to form liquid complexes while maintaining their α‐helical secondary structure. Coupling the α‐helical polypeptide to a neutral, hydrophilic polymer and subsequent complexation enables the formation of nanoscale coacervate‐core micelles. While previous reports on polypeptide complexation demonstrated a critical dependence of the nature of the complex (liquid versus solid) on chirality, the α‐helical structure of the positively charged polypeptide prevents the formation of β‐sheets, which would otherwise drive the assembly into a solid state, thereby, enabling coacervate formation between two chiral components. The higher charge density of the assembly, a result of the folding of the α‐helical polypeptide, provides enhanced resistance to salts known to inhibit polypeptide complexation. The unique combination of properties of these materials can enhance the known potential of fluid polypeptide complexes for delivery of biologically relevant molecules.     

Self‐Assembly of a Four‐Helix Bundle on a DNA Quadruplex

Come together : A novel method for assembling monomers and controlling structure of a de novo helix bundle protein is described. A guanine (G)‐rich oligodeoxynucleotide scaffold forms a hydrogen‐bonded DNA quadruplex in the presence of potassium counterions, thereby inducing a helical structure and fourfold stoichiometry in conjugated, amphiphilic peptide sequences. The DNA scaffold shows potential for rapidly assembling designed proteins.

     

Structural Diversity in the Self‐Assembly of Pseudopeptidic Macrocycles

The self‐assembling abilities of several pseudopeptidic macrocycles have been thoroughly studied both in the solid (SEM, TEM, FTIR) and in solution (NMR, UV, CD, FTIR) states. Detailed microscopy revealed large differences in the morphology of the self‐assembling micro/nanostructures depending on the macrocyclic chemical structures. Self‐assembly was triggered by the presence of additional methylene groups or by changing from para to meta geometry of the aromatic phenylene backbone moiety. More interestingly, the nature of the side chain also plays a fundamental role in some of the obtained nanostructures, thus producing structures from long fibers to hollow spheres. These nanostructures were obtained in different solvents and on different surfaces, thus implying that the chemical information for the self‐assembly is contained in the molecular structure. Dilution NMR studies (chemical shift and self‐diffusion rates) suggest the formation of incipient aggregates in solution by a combination of hydrogen‐bonding and π–π interactions, thus implicating amide and aryl groups, respectively. Electronic spectroscopy further supports the π–π interactions because the compounds that lead to fibers show large hypochromic shifts in the UV spectra. Moreover, the fiber‐forming macrocycles also showed a more intense CD signature. The hydrogen‐bonding interactions within the nanostructures were also characterized by attenuated total‐reflectance FTIR spectroscopy, which allowed us to monitor the complete transition from the solution to the dried nanostructure. Overall, we concluded that the self‐assembly of this family of pseudopeptidic macrocycles is dictated by a synergic action of hydrogen‐bonding and π–π interactions. The feasibility and geometrical disposition of these interactions finally render a hierarchical organization, which has been rationalized with a proposal of a model. The understanding of the process at the molecular level has allowed us to prepare hybrid soft materials.     

Redox‐Controlled Helical Self‐Assembly of a Polyoxometalate Complex

Polyoxometalate (POM) complex (DODA)₂[Mo₆O₁₉] with a symmetrical linear structure was prepared conveniently by replacing the tetrabutylammonium (TBA) counterions of Lindquist‐type cluster (TBA)₂[Mo₆O₁₉] with cationic surfactant dioctadecyldimethylammonium (DODA). A helical self‐assembled structure of the complex was formed in dichloromethane/propanol. The dynamically reversible transformation between helical and spherical assemblies on alternate UV irradiation and H₂O₂ oxidation was characterized by SEM, TEM, and UV/Vis studies. The redox‐controlled morphology change is modulated by variation of the electrostatic interactions between the inorganic polyanion and the organic cation DODA through controlling the redox properties of the POM component, as shown by the XRD, X‐ray photoelectron spectroscopic, and ¹H NMR measurements. The strategy applied herein is a unique example of targeted smart and helical assembly of POM complexes.     

Helical‐Ribbon Formation by a β‐Amino Acid Modified Amyloid β‐Peptide Fragment

An addition to the family : The introduction of β‐amino acid residues into a modified amyloid β peptide fragment resulted in well‐defined helical nanoribbons (see cryo‐TEM image) comprising β strands mainly oriented perpendicular to the ribbon axis. The nanoribbons order into a flow‐aligning nematic phase at higher concentration. The β‐strand nanoribbon structure is an addition to the known set of secondary structures adopted by β‐peptides.

     

Evolution of a Constitutional Dynamic Library Driven by Self‐Organisation of a Helically Folded Molecular Strand

Conversion of macrocyclic imine entities into helical strands was achieved through three‐ and four‐component exchange reactions within constitutionally dynamic libraries. The generation of sequences of the intrinsic helicity codon, based on the hydrazone–pyrimidine fragment obtained by condensation of pyrimidine dialdehyde A with pyrimidine bis‐hydrazine B , shifted the equilibrium between all the possible macrocycles and strands towards the full expression (>98%) of helical product [ A / B ]. Furthermore, it was shown that chain folding accelerated the dynamic exchange reactions among the library members. Lastly, in four‐component experiments (involving A , B , E and either C or D ), even though the macrocyclic entities ([ A / C ], [ B / E ]; [ A / D ], [ B / E ]) were the kinetically preferred products, over time dialdehyde A relinquished its initial diamine partners C or D to opt for bis‐hydrazine B , which allowed the preferential formation of the helically folded strand. The present results indicate that self‐organisation pressure was able to drive the dynamic system towards the selective generation of the strand undergoing helical folding.     

Flow‐Enabled Self‐Assembly of Large‐Scale Aligned Nanowires

One‐dimensional nanowires enable the realization of optical and electronic nanodevices that may find applications in energy conversion and storage systems. Herein, large‐scale aligned DNA nanowires were crafted by flow‐enabled self‐assembly (FESA). The highly oriented and continuous DNA nanowires were then capitalized on either as a template to form metallic nanowires by exposing DNA nanowires that had been preloaded with metal salts to an oxygen plasma or as a scaffold to direct the positioning and alignment of metal nanoparticles and nanorods. The FESA strategy is simple and easy to implement and thus a promising new method for the low‐cost synthesis of large‐scale one‐dimensional nanostructures for nanodevices.     

Synthesis of Aromatic Macrocyclic Amphiphiles and their Self‐Assembling Behavior in Aqueous Solution

A triblock amphiphilic macrocycle consisting of a macrocyclic aromatic segment, a hydrophilic oligo(ethylene oxide) branch, and a hydrophobic alkyl dendron is successfully synthesized and characterized. The resulting cyclic amphiphile is observed to self‐assemble into hollow double‐layered capsules in aqueous solution, as confirmed by dynamic light scattering and cryogenic transmission electron microscopy investigations. The capsules are able to encapsulate hydrophobic guest molecules through aromatic interactions with high stability.

     

Seed‐Mediated Synthesis of Single‐Crystal Gold Nanospheres with Controlled Diameters in the Range 5–30 nm and their Self‐Assembly upon Dilution

Single‐crystal gold nanospheres with controlled diameters in the range 5–30 nm were synthesized by using a facile approach that was based on successive seed‐mediated growth. The key to the success of this synthesis was the use of hexadecyltrimethylammonium chloride (CTAC) as a capping agent and a large excess of ascorbic acid as a reductant to ensure fast reduction and, thus, single crystallinity and a spherical shape of the resultant nanoparticles. The diameters of the gold nanospheres could be readily controlled by varying the amount of seeds that were introduced into the reaction system. The gold nanospheres could be produced with uniform diameters of up to 30 nm; thus, their localized surface plasmon resonance properties could be directly compared with the results that were obtained from theoretical calculations. Interestingly, we also found that these gold nanospheres self‐assembled into dimers, larger aggregates, and wavy nanowires when they were collected by centrifugation, dispersed in deionized water, and then diluted to different volumes with deionized water.     

Exploiting Aromatic Interactions for β‐Peptide Foldamer Helix Stabilization: A Significant Design Element

Tetrameric H10/12 helix stabilization was achieved by the application of aromatic side‐chains in β‐peptide oligomers by intramolecular backbone–side chain CH–π interactions. Because of the enlarged hydrophobic surface of the oligomers, a further aim was the investigation of the self‐assembly in a polar medium for the β‐peptide H10/12 helices. NMR, ECD, and molecular modeling results indicated that the oligomers formed by cis‐[1S,2S]‐ or cis‐[1R,2R]‐1‐amino‐1,2,3,4‐tetrahydronaphthalene‐2‐carboxylic acid (ATENAC) and cis‐[1R,2S]‐ or cis‐[1S,2R]‐2‐aminocyclohex‐3‐enecarboxylic acid (ACHEC) residues promote stable H10/12 helix formation with an alternating backbone configuration even at the tetrameric chain length. These results support the view that aromatic side‐chains can be applied for helical structure stabilization. Importantly, this is the first observation of a stable H10/12 helix with tetrameric chain‐length. The hydrophobically driven self‐assembly was achieved for the helix‐forming oligomers, seen as vesicles in transmission electron microscopy images. The self‐association phenomenon, which supports the helical secondary structure of these oligomers, depends on the hydrophobic surface area, because a higher number of aromatic side‐chains yielded larger vesicles. These results serve as an essential element for the design of helices relating to the H10/12 helix. Moreover, they open up a novel area for bioactive foldamer construction, while the hydrophobic area gained through the aromatic side‐chains may yield important receptor–ligand interaction surfaces, which can provide amplified binding strength.     

Herringbone and Helical Self‐Assembly of π‐Conjugated Molecules in the Solid State through CH/π Hydrogen Bonds

Self‐organization of organic molecules through weak noncovalent forces such as CH/π interactions and creation of large hierarchical supramolecular structures in the solid state are at the very early stage of research. The present study reports direct evidence for CH/π interaction driven hierarchical self‐assembly in π‐conjugated molecules based on custom‐designed oligophenylenevinylenes (OPVs) whose structures differ only in the number of carbon atoms in the tails. Single‐crystal X‐ray structures were resolved for these OPV synthons and the existence of long‐range multiple‐arm CH/π interactions was revealed in the crystal lattices. Alignment of these π‐conjugated OPVs in the solid state was found to be crucial in producing either right‐handed herringbone packing in the crystal or left‐handed helices in the liquid‐crystalline mesophase. Pitch‐ and roll‐angle displacements of OPV chromophores were determined to trace the effect of the molecular inclination on the ordering of hierarchical structures. Furthermore, circular dichroism studies on the OPVs were carried out in the aligned helical structures to prove the existence of molecular self‐assembly. Thus, the present strategy opens up new approaches in supramolecular chemistry based on weak CH/π hydrogen bonding, more specifically in π‐conjugated materials.