Yongju Kim

Development of Toroidal Nanostructures by Self-Assembly: Rational Designs and Applications

Toroidal nanostructures are symmetrical ring-shaped structures with a central internal pore. Interestingly, in nature, many transmembrane proteins such as β-barrels and α-helical bundles have toroidal shapes. Because of this similarity, toroidal nanostructures can provide a template for the development of transmembrane channels. However, because of the lack of guiding principles for the construction of toroids, researchers have not widely studied the self-assembly of toroidal nanostructures as compared with the work on other supramolecular architectures. In this Account, we describe our recent efforts to construct toroidal nanostructures through the self-assembly of rationally designed building blocks. In one strategy for building these structures, we induce interfacial curvatures within the building blocks. When we laterally graft a bulky hydrophilic segment onto a p-oligophenyl rod or β-sheet peptides, the backbones of the self-assembled structures can bend in response to the steric effect of these large side groups, driving the p-oligophenyl rod or β-sheet peptides to form nanosized toriods. In another strategy, we can build toroids from bent-shaped building blocks by stacking the macrocycles. Aromatic segments with an internal angle of 120° can associate with each other in aqueous solution to form a hexameric macrocycle. Then these macrocycles can stack on top of each other via hydrophobic and π-π interactions and form highly uniform toroidal nanostructures. We provide many examples that illustrate these guiding principles for constructing toroidal nanostructures in aqueous solution. Efforts to create toroidal nanostructures through the self-assembly of elaborately designed molecular modules provide a fundamental approach toward the development of artificial transmembrane channels. Among the various toroids that we developed, a few nanostructures can insert into lipid membranes and allow limited transport in vesicles.

Supramolecular Switching between Flat Sheets and Helical Tubules Triggered by Coordination Interaction

Here we report the spontaneous formation of switchable sheets in aqueous solution, which is based on bent-shaped aromatic amphiphiles containing m-pyridine units at the terminals and a hydrophilic dendron at the apex. The aromatic segments self-assemble into flat sheets consisting of a zigzag conformation through π-π stacking interactions. Notably, the sheets reversibly transform into helical tubules at higher concentration and into discrete dimeric macrocycles at a lower concentration in response to Ag(I) ions through reversible coordination interactions between the pyridine units of the aromatic segments and the Ag(I) ions. While maintaining the coordination bonding interactions, the helical tubules reversibly transform into the dimeric macrocycles in response to the variation in concentration.

Intelligent supramolecular assembly of aromatic block molecules in aqueous solution

The construction of supramolecular nanoscopic architectures has been intensively pursued because of their unique features for applications in nanoscience and biomimetic chemistry. Molecular self-assemblies of aromatic rod-coil amphiphiles consisting of rigid rod segments and hydrophilic flexible chains in aqueous solution provide a facile avenue into this area. This feature article highlights the recent progress regarding the construction of aqueous assemblies that result from the sophisticated design of aromatic rod-coils, with the aim to develop stimuli-responsive systems and bioactive materials. Important factors affecting the self-assembly morphologies are discussed and summarized. Dynamic structural changes triggered by temperature and guest molecules are demonstrated. Finally, the perspective of bioactive nanostructures originated from self-assembly of aromatic block amphiphiles is also introduced.

Switchable Nanoporous Sheets by the Aqueous Self‐Assembly of Aromatic Macrobicycles

The molecular self-assembly of aromatic building blocks is a powerful approach to the construction of dynamic nanostructures that are able to respond to external stimuli by changing their shape and/or macroscopic properties. In this context, it is possible to modulate the interplay between multiple noncovalent interactions through the rational design of molecular modules. The directionality of these interactions plays a critical role in controlling the shape of the selfassembled structures. Laterally grafted rod building blocks lead to one-dimensional nanofibers through unidirectional guiding of the elongated aromatic rods in the self-assembly process. Anisotropic micelles also undergo directional growth to form low-dimensional supramolecular structures in selected solvents. For example, hydrophobic oblate micelles with hydrophilic side faces stack on top of each other to form 1D nanofibers. On the other hand, hydrophobic aromatic rod bundles with hydrophilic up and down grow through side-to-side interactions to form freely suspended 2D structures in bulk solution. A reduction in the strength of the aromatic interactions leads the resulting planar sheets to form 2D networks. However, the elaborate construction of 2D structures requires the rational design of molecular building blocks that are able to grow in two dimensions. One possibility is the sideby-side arrangement of 2D molecular building blocks, such as flat disk-shaped aromatic molecules. Nonetheless, most flat aromatic amphiphiles stack together through face-to-face interactions to form nanofibers. 7] To frustrate continuous aromatic stacking in one dimension, one can introduce flexible chains on the basal plane of the aromatic structures. The basal-plane chains should enforce a lateral arrangement of the flat aromatic segments and their two-dimensional growth rather than growth through conventional 1D aromatic stacking (Figure 1). With this idea in mind, we designed a flat aromatic bicycle with a hydrophilic dendron at the center of the basal plane. Another important issue regarding 2D planar structures is the possibility of the integration of dynamic response characteristics triggered by environmental changes. The combination of principles of 2D planar structures with responsive properties would generate a new class of intelligent nanomaterials. Herein we report the spontaneous formation of 2D porous sheets in aqueous solution through the two-dimensional selfassembly of an aromatic macrobicycle with a hydrophilic dendron attached to its basal plane. Remarkably, unlike conventional nanoporous materials, the resulting porous sheets underwent dynamic motion between open and closed states, as triggered by guest intercalation (Figure 4). The self-assembling molecules that form this aggregate consist of a macrobicyclic aromatic segment and a hydrophilic oligoether dendron grafted at the center of the basal plane (Figure 1). The synthesis of the flat aromatic amphiphiles began with the Sonogashira coupling of a dendron-substituted diiodobenzene derivative with 2,6-dibromoethynylbenzene to provide a tetrabromo building block (see the Supporting Information). Suzuki coupling of the tetrabromo compound with 3-((triisopropylsilyl)ethynyl)phenylboronic acid ester, followed by silyl-group deprotection with tetra-n-butylammonium fluoride, then provided a precursor with four terminal alkyne groups. The final aromatic amphiphiles were synthesized efficiently by intramolecular Glaser-type coupling of the terminal alkyne groups under dilute reaction Figure 1. Molecular structure of aromatic macrobicycles with dendrons attached to their basal plane and schematic representation of the 2D growth of the flat micelles derived by pairwise stacking.

Open–closed switching of synthetic tubular pores

While encouraging progress has been made on switchable nanopores to mimic biological channels and pores, it remains a great challenge to realize long tubular pores with a dynamic open–closed motion. Here we report μm-long, dynamic tubular pores that undergo rapid switching between open and closed states in response to a thermal signal in water. The tubular walls consist of laterally associated primary fibrils stacked from disc-shaped molecules in which the discs readily tilt by means of thermally regulated dehydration of the oligoether chains placed on the wall surfaces. Notably, this pore switching mediates a controlled water-pumping catalytic action for the dehydrative cyclization of adenosine monophosphate to produce metabolically active cyclic adenosine monophosphate. We believe that our work may allow the creation of a variety of dynamic pore structures with complex functions arising from open–closed motion.

Guest-Driven Inflation of Self-Assembled Nanofibers through Hollow Channel Formation

The highlight of self-assembly is the reversibility of various types of noncovalent interactions which leads to construct smart nanostructures with switchable pores. Here, we report the spontaneous formation of inflatable nanofibers through the formation of hollow internal channels triggered by guest encapsulation. The molecules that form this unique nanofibers consist of a bent-shaped aromatic segment connected by a m-pyridine unit and a hydrophilic dendron at its apex. The aromatic segments self-assemble into paired dimers which stack on top of one another to form thin nanofibers with pyridine-functionalized aromatic cores. Notably, the nanofibers reversibly inflate into helical tubules through the formation of hollow cavities triggered by p-phenylphenol, a hydrogen-bonding guest. The reversible inflation of the nanofibers arises from the packing rearrangements in the aromatic cores from transoid dimers to cisoid macrocycles driven by the reversible hydrogen-bonding interactions between the pyridine units of the aromatic cores and the p-phenylphenol guest molecules.

Directional assembly of α-helical peptides induced by cyclization.

Effective stabilization of short peptide chains into a helical structure has been a challenge in the fields of chemistry and biology. Here we report a novel method for α-helix stabilization of short peptides through their confinement in a cyclic architecture. We synthesized block peptides based on a short peptide and a flexible linker as linear precursors. Subsequent cyclization of the peptide precursors resulted in a conformational change of the peptide unit from a random coil to an α-helix. The incorporation of hydrophobic residues into the peptide unit led to a facially amphiphilic conformation of the molecular cycle. The resulting amphiphilic peptide self-assembled into undulated nanofibers through the directional assembly of small oblate micelles.

Spontaneous Capture of Carbohydrate Guests through Folding and Zipping of Self-Assembled Ribbons

One of the great challenges in molecular self-assembly is how to confer self-folding and closing characteristics on flat two-dimensional structures in response to external triggers. Herein, we report a planar ribbon assembly that folds into closed tubules in response to fructose. The ribbons, ≈28 nm wide and 3.5 nm thick, consist of 8 laterally-associated elementary fibrils in which disc-shaped macrocycle amphiphiles are stacked along their axis. Upon addition of fructose, these flat structures spontaneously fold into closed tubules, with an outer diameter of ≈8 nm, through zipping of the two sides of the ribbons. Notably, the folding and then zipping of the flat ribbons is accompanied by spontaneous capture of the fructose molecules inside the tubular cavities.

Reversible, Short α-Peptide Assembly for Controlled Capture and Selective Release of Enantiomers

Although significant progress has been achieved with short peptide nanostructures, the construction of switchable membrane assemblies remains a great challenge. Here we report short α-peptide assemblies that undergo thermo-reversible switching between assembly and disassembly states, triggered by the conformational change of laterally grafted short peptides from a folded α-helix to a random coil conformation. The α-helical peptide based on two oligoether dendron side groups forms flat disks, while the peptide helix based on three dendron side groups forms hollow vesicles. The vesicular membrane can spontaneously capture a racemic mixture through the self-formation of vesicular containers upon heating and enantioselectively release the chiral guest molecule through preferential diffusion across the vesicular walls.

Collective helicity switching of a DNA–coat assembly

Hierarchical assemblies of biomolecular subunits can carry out versatile tasks at the cellular level with remarkable spatial and temporal precision. As an example, the collective motion and mutual cooperation between complex protein machines mediate essential functions for life, such as replication, synthesis, degradation, repair and transport. Nucleic acid molecules are far less dynamic than proteins and need to bind to specific proteins to form hierarchical structures. The simplest example of these nucleic acid-based structures is provided by a rod-shaped tobacco mosaic virus, which consists of genetic material surrounded by coat proteins. Inspired by the complexity and hierarchical assembly of viruses, a great deal of effort has been devoted to design similarly constructed artificial viruses. However, such a wrapping approach makes nucleic acid dynamics insensitive to environmental changes. This limitation generally restricts, for example, the amplification of the conformational dynamics between the right-handed B form to the left-handed Z form of double-stranded deoxyribonucleic acid (DNA). Here we report a virus-like hierarchical assembly in which the native DNA and a synthetic coat undergo repeated collective helicity switching triggered by pH change under physiological conditions. We also show that this collective helicity inversion occurs during translocation of the DNA-coat assembly into intracellular compartments. Translating DNA conformational dynamics into a higher level of hierarchical dynamics may provide an approach to create DNA-based nanomachines.