Aqueous Supramolecular Transformations of Motor Bola-Amphiphiles at Multiple Length-Scale.

Molecular motor amphiphiles have already been widely attempted for dynamic nanosystems across multiple length-scale for developments of small functional materials, including controlling macroscopic foam properties, amplifying motion as artificial molecular muscles, and serving as extracellular matrix mimicking cell scaffolds. However, limiting examples of bola-type molecular motor amphiphiles are considered for constructing macroscopic biomaterials. Herein, this work presents the designed two second generation molecular motor amphiphiles, motor bola-amphiphiles (MBAs). Aside from the photoinduced motor rotation of MBAs achieved in both organic and aqueous media, the rate of recovering thermal helix inversion step can be controlled by the rotor part with different steric hindrances. Dynamic assembled structures of MBAs are observed under (cryo)-transmission electron microscopy (TEM). This dynamicity assists MBAs in further assembling as macroscopic soft scaffolds by applying a shear-flow method. Upon photoirradiation, the phototropic bending function of MBA scaffolds is observed, demonstrating the amplification of molecular motion into macroscopic phototropic bending functions at the macroscopic length-scale. Since MBAs are confirmed with low cytotoxicity, human bone marrow-derived mesenchymal stem cells (hBM-MSCs) can grow on the surface of MBA scaffolds. These results clearly demonstrate the concept of designing MBAs for developing photoresponsive dynamic functional materials to create new-generation soft robotic systems and cell-material interfaces.

Red-light-controlled supramolecular assemblies of indigo amphiphiles at multiple length scales.

Amphiphilic molecules functionalized with photoresponsive motifs have attractive prospects for applications in smart functional bio-material ranging from cell-material interfaces to drug delivery systems owing to the precisely controllable functionality of self-assembled hierarchical supramolecular structures in aqueous media by a non-invasive light stimulation with high temporal- and spatial-resolution. However, most of reported photoresponsive amphiphiles are triggered by bio-damaging UV-light, which greatly limits the potential in bio-related applications. Herein, we present newly designed red-light controlled N,N'-diaryl-substituted indigo amphiphiles (IA), exhibiting excellent photoswitchablity and photostability with dual red-/green-light in organic media. Meanwhile, aqueous solutions of IA assembled into supramolecular structures in both microscopic and macroscopic length-scale, though the photoresponsiveness of IA is slightly compromised in aqueous media. At macroscopic length-scale, morphological changes of IA macroscopic scaffold prepared by a shear-flow method can be fine adjusted upon red-light irradiation. Moreover, the preferential attachment of live h-MSCs to IA macroscopic scaffold surface also indicates a good biocompatibility of IA macroscopic scaffold. These results provide the potential for developing the next generation of red-light controlled soft functional materials with good biocompatibility.

Tailoring Multicontrolled Supramolecular Assemblies of Stiff-Stilbene Amphiphiles into Macroscopic Soft Scaffolds as Cell-Material Interfaces.

Biocompatible synthetic supramolecular systems have shed light on biomedical and tissue-regenerative material applications. The intrinsic functional applicability, tunability, and stimuli-responsiveness of synthetic supramolecular systems allow one to develop various multicontrolled supramolecular assemblies in aqueous media. However, it remains highly challenging to use state-of-the-art supramolecular assemblies of photoresponsive amphiphiles controlled by multiple stimulations in fabricating macroscopic materials. Herein, we demonstrate a stiff-stilbene amphiphile (SA) multicontrolled supramolecular assembling system that comprises two different charged end groups. The excellent photoswitchabilities of SA in both organic and aqueous media are demonstrated. Furthermore, multiple stimuli, i.e., light, pH, and counterions, are applied to control the supramolecular assembling behaviors, which are monitored by circular dichroism spectroscopy and electron microscopies. This multicontrolled supramolecular system can be systematically assembled into macroscopic soft functional scaffolds, whose structural parameters are investigated by electron microscopies and X-ray diffraction techniques, suggesting the large aspect ratio of SA nanostructures assembled into macroscopic soft scaffolds. The fabricated soft functional scaffold is highly biocompatible for photocontrolled biotarget encapsulation/release selectively, as well as a cell-material interface for diverse cells' attachment. This new synthetic multicontrolled soft functional material provides a new strategy toward the development of next-generation controllable and biocompatible soft functional materials.

Controlled Supramolecular Assemblies of Chiral Cyclometalated Gold (III) Amphiphiles in Aqueous Media.

Gold (III) cyclometalated based amphiphiles in aqueous media have been revealed with excellent supramolecular transformations to external stimuli to open new pathways for soft functional material fabrications. Herein, we report a new chiral cyclometalated gold (III) amphiphile (GA) assembling into lamellar nanostructures in aqueous media confirmed with transmission electron microscopy (TEM). Counterion exchange with D-, L-, or racemic-camphorsulfonates features the significant supramolecular helicity enhancements, enabling transformations of GA from lamellar structure to vesicles and to nanotubes with multi-equivalents of counterion. The limited cytotoxicity of GA in aqueous media exhibits good biocompatibility.

Controlled Supramolecular Assemblies of Chiral Cyclometalated Gold (III) Amphiphiles in Aqueous Media.

Invited for this month's cover are the collaborating groups of Prof. Man-Kin Wong and Dr. Franco King-Chi Leung from The Hong Kong Polytechnic University. The cover picture illustrates chiral gold (III) amphiphiles assemble into tubular supramolecular structures in aqueous media through counterion controlled pathway. The nanostructures were further demonstrated with good cytocompatibility in aqueous media. More information can be found in the Research Article by Man-Kin Wong, Franco King-Chi Leung, and co-workers.

Smart Design of Nanostructures for Boosting Tumor Immunogenicity in Cancer Immunotherapy.

Although tumor immunotherapy has emerged as a promising therapeutic method for oncology, it encounters several limitations, especially concerning low response rates and potential off-targets that elicit side effects. Furthermore, tumor immunogenicity is the critical factor that predicts the success rate of immunotherapy, which can be boosted by the application of nanotechnology. Herein, we introduce the current approach of cancer immunotherapy and its challenges and the general methods to enhance tumor immunogenicity. Importantly, this review highlights the integration of anticancer chemo/immuno-based drugs with multifunctional nanomedicines that possess imaging modality to determine tumor location and can respond to stimuli, such as light, pH, magnetic field, or metabolic changes, to trigger chemotherapy, phototherapy, radiotherapy, or catalytic therapy to upregulate tumor immunogenicity. This promotion rouses immunological memory, such as enhanced immunogenic cell death, promoted maturation of dendritic cells, and activation of tumor-specific T cells against cancer. Finally, we express the related challenges and personal perspectives of bioengineered nanomaterials for future cancer immunotherapy.

Exploration of molecular machines in supramolecular soft robotic systems.

Soft robotic system, a new era of material science, is rapidly developing with advanced processing technology in soft matters, featured with biomimetic nature. An important bottom-up approach is through the implementation of molecular machines into polymeric materials, however, the synchronized molecular motions, acumination of strain across multiple length-scales, and amplification into macroscopic actuations remained highly challenging. This review presents the significances, key design strategies, and outlook of the hierarchical supramolecular systems of molecular machines to develop novel types of supramolecular-based soft robotic systems.

Visible-light controlled supramolecular transformations of donor-acceptor Stenhouse adducts amphiphiles at multiple length-scale.

Designing responsive, adaptive, and dynamic supramolecular systems in water, the incorporation of photoresponsive units in amphiphilic molecular structures enables functional responses in a non-invasive way by using light. However, in aqueous media, vast majority of reported synthetic photoresponsive molecular amphiphiles are commonly driven by high energy and bio-damaging UV-light for supramolecular transformation at multiple length-scale. Herein, we present newly designed visible-light controlled supramolecular assembly of donor-acceptor Stenhouse adducts amphiphiles (DA) with excellent stability and solubility in aqueous media. The excellent photoswitchability in organic media and photoresponsiveness in aqueous media driven by visible-light are found, as confirmed with UV-vis absorption and NMR spectroscopies. Supramolecular assembly at multiple length-scale of DAs is investigated with electron microscopies and X-ray diffraction to show large aspect-ratio of nanostructures assembled into macroscopic soft scaffolds. Upon visible-light irradiation, the large geometrical transformation of DAs enables supramolecular transformations, and subsequently destabilizes the macroscopic soft scaffold to release fluorophores from the scaffolds. These results provide the feasibility in developing the next generation of visible-light controlled macroscopic soft functional scaffold from supramolecular assembly across multiple length-scale without and offer ample opportunity to design future soft robotic materials and functional biomaterials.

Aqueous Supramolecular Co-Assembly of Anionic and Cationic Photoresponsive Stiff-Stilbene Amphiphiles.

Fabrication of macroscopic soft functional materials, such as macroscopic photoresponsive soft materials and artificial muscles, can be commonly prepared by charge screening of supramolecular assemblies with inorganic salt solutions using a shear-flow method. However, some of the charged end-groups of photoresponsive molecular amphiphiles cannot be stabilized with inorganic salt solutions to fabricate macroscopic soft materials. Stiff stilbene amphiphiles (SAs) functionalized with anionic phosphite and cationic quaternary ammonium end groups are designed and synthesized and their photochemical and supramolecular assembly properties are determined. Supramolecular co-assembly of anionic and cationic nanotubes of SAs allows to transform into nanoribbons, confirmed by transmission electron microscopy, critical aggregation concentration, and Zeta potential measurements. Nanoribbons of anionic and cationic SAs can be prepared into macroscopic soft materials with inorganic salt solutions and surprisingly also with deionized water. The macroscopic soft material of anionic and cationic SAs can be stabilized at low concentration ≈5 mm. Meanwhile, the photoresponsiveness of the macroscopic soft materials is retained to provide macroscopic morphological change upon photoirradiation. These results exhibit the feasibility in fabrication of macroscopic functional soft materials from supramolecular assembly across multiple length-scale without help of inorganic salts and offer ample opportunity in developing future soft supramolecular robotic systems.

Photoactuating Artificial Muscles of Motor Amphiphiles as an Extracellular Matrix Mimetic Scaffold for Mesenchymal Stem Cells.

Mimicking the native extracellular matrix (ECM) as a cell culture scaffold has long attracted scientists from the perspective of supramolecular chemistry for potential application in regenerative medicine. However, the development of the next-generation synthetic materials that mimic key aspects of ECM, with hierarchically oriented supramolecular structures, which are simultaneously highly dynamic and responsive to external stimuli, remains a major challenge. Herein, we present supramolecular assemblies formed by motor amphiphiles (MAs), which mimic the structural features of the hydrogel nature of the ECM and additionally show intrinsic dynamic behavior that allow amplifying molecular motions to macroscopic muscle-like actuating functions induced by light. The supramolecular assembly (named artificial muscle) provides an attractive approach for developing responsive ECM mimetic scaffolds for human bone marrow-derived mesenchymal stem cells (hBM-MSCs). Detailed investigations on the photoisomerization by nuclear magnetic resonance and UV-vis absorption spectroscopy, assembled structures by electron microscopy, the photoactuation process, structural order by X-ray diffraction, and cytotoxicity are presented. Artificial muscles of MAs provide fast photoactuation in water based on the hierarchically anisotropic supramolecular structures and show no cytotoxicity. Particularly important, artificial muscles of MAs with adhered hBM-MSCs still can be actuated by external light stimulation, showing their ability to convert light energy into mechanical signals in biocompatible systems. As a proof-of-concept demonstration, these results provide the potential for building photoactuating ECM mimetic scaffolds by artificial muscle-like supramolecular assemblies based on MAs and offer opportunities for signal transduction in future biohybrid systems of cells and MAs.

From Photoinduced Supramolecular Polymerization to Responsive Organogels.

Controlling supramolecular polymerization by external stimuli holds great potential toward the development of responsive soft materials and manipulating self-assembly at the nanoscale. Photochemical switching offers the prospect of regulating the structure and properties of systems in a noninvasive and reversible manner with spatial and temporal control. In addition, this approach will enhance our understanding of supramolecular polymerization mechanisms; however, the control of molecular assembly by light remains challenging. Here we present photoresponsive stiff-stilbene-based bis-urea monomers whose trans isomers readily form supramolecular polymers in a wide range of organic solvents, enabling fast light-triggered depolymerization-polymerization and reversible gel formation. Due to the stability of the cis isomers and the high photostationary states (PSS) of the cis-trans isomerization, precise control over supramolecular polymerization and in situ gelation could be achieved with short response times. A detailed study on the temperature-dependent and photoinduced supramolecular polymerization in organic solvents revealed a kinetically controlled nucleation-elongation mechanism. By application of a Volta phase plate to enhance the phase-contrast method in cryo-EM, unprecedented for nonaqueous solutions, uniform nanofibers were observed in organic solvents.

Self-Assembly of Photoresponsive Molecular Amphiphiles in Aqueous Media.

Amphiphilic molecules, comprising hydrophobic and hydrophilic moieties and the intrinsic propensity to self-assemble in aqueous environment, sustain a fascinating spectrum of structures and functions ranging from biological membranes to ordinary soap. Facing the challenge to design responsive, adaptive, and out-of-equilibrium systems in water, the incorporation of photoresponsive motifs in amphiphilic molecular structures offers ample opportunity to design supramolecular systems that enables functional responses in water in a non-invasive way using light. Here, we discuss the design of photoresponsive molecular amphiphiles, their self-assembled structures in aqueous media and at air-water interfaces, and various approaches to arrive at adaptive and dynamic functions in isotropic and anisotropic systems, including motion at the air-water interface, foam formation, reversible nanoscale assembly, and artificial muscle function. Controlling the delicate interplay of structural design, self-assembling conditions and external stimuli, these responsive amphiphiles open several avenues towards application such as soft adaptive materials, controlled delivery or soft actuators, bridging a gap between artificial and natural dynamic systems.

Modulation of porosity in a solid material enabled by bulk photoisomerization of an overcrowded alkene.

The incorporation of photoswitchable molecules into solid-state materials holds promise for the fabrication of responsive materials, the properties of which can be controlled on-demand. However, the possible applications of these materials are limited due to the restrictions imposed by the solid-state environment on the incorporated photoswitches, which render the photoisomerization inefficient. Here we present responsive porous switchable framework materials based on a bistable chiroptical overcrowded alkene incorporated in the backbone of a rigid aromatic framework. As a consequence of the high intrinsic porosity, the resulting framework readily responds to a light stimulus, as demonstrated by solid-state Raman and reflectance spectroscopies. Solid-state 13C NMR spectroscopy highlights an efficient and quantitative bulk photoisomerization of the incorporated light-responsive overcrowded olefins in the solid material. Taking advantage of the quantitative photoisomerization, the porosity of the framework and the consequent gas adsorption can be reversibly modulated in response to light and heat.

Multi-modal control over the assembly of a molecular motor bola-amphiphile in water.

We report multi-modal-control over the assembly behaviour of a first-generation molecular motor bola-amphiphile in water by light, pH and the choice of counter-ions. These findings open up opportunities for the development of materials that reconfigurate enabling complex functions in response to different stimuli.

Dynamic Assemblies of Molecular Motor Amphiphiles Control Macroscopic Foam Properties.

Stimuli-responsive supramolecular assemblies controlling macroscopic transformations with high structural fluidity, i.e., foam properties, have attractive prospects for applications in soft materials ranging from biomedical systems to industrial processes, e.g., textile coloring. However, identifying the key processes for the amplification of molecular motion to a macroscopic level response is of fundamental importance for exerting the full potential of macroscopic structural transformations by external stimuli. Herein, we demonstrate the control of dynamic supramolecular assemblies in aqueous media and as a consequence their macroscopic foam properties, e.g., foamability and foam stability, by large geometrical transformations of dual light/heat stimuli-responsive molecular motor amphiphiles. Detailed insight into the reversible photoisomerization and thermal helix inversion at the molecular level, supramolecular assembly transformations at the microscopic level, and the stimuli-responsive foam properties at the macroscopic level, as determined by UV-vis absorption and NMR spectroscopies, electron microscopy, and foamability and in situ surface tension measurements, is presented. By selective use of external stimuli, e.g., light or heat, multiple states and properties of macroscopic foams can be controlled with very dilute aqueous solutions of the motor amphiphiles (0.2 weight%), demonstrating the potential of multiple stimuli-responsive supramolecular systems based on an identical molecular amphiphile and providing opportunities for future soft materials.

Dual-Controlled Macroscopic Motions in a Supramolecular Hierarchical Assembly of Motor Amphiphiles.

Three-dimensional unidirectionally aligned and responsive supramolecular hierarchical assemblies have much potential in adaptive materials for biomedical and soft actuator applications. However, to achieve systematical control of the motion of stimuli-responsive materials by orthogonal external stimuli and to complete a series of complicated tasks remains a grand challenge. Herein, we demonstrate a novel designed hybrid supramolecular assembly of molecular motor amphiphiles that also serves as a template for iron nanoparticles growth, and as a consequence this soft hybrid material is orthogonally controlled by dual light/magnetic stimuli. Macroscopic motor amphiphile strings, decorated with iron nanoparticles, provide fast response photoactuations and magnet induced movements that allows a precisely controlled cargo transport process.

Supramolecular Packing and Macroscopic Alignment Controls Actuation Speed in Macroscopic Strings of Molecular Motor Amphiphiles.

Three-dimensional organized unidirectionally aligned and responsive supramolecular structures have much potential in adaptive materials ranging from biomedical components to soft actuator systems. However, to control the supramolecular structure of these stimuli responsive, for example photoactive, materials and control their actuation remains a major challenge. Toward the design of "artificial muscles", herein, we demonstrate an approach that allows hierarchical control of the supramolecular structure, and as a consequence its photoactuation function, by electrostatic interaction between motor amphiphiles (MA) and counterions. Detailed insight into the effect of various ions on structural parameters for self-assembly from nano- to micrometer scale in water including nanofiber formation and nanofiber aggregation as well as the packing structure, degree of alignment, and actuation speed of the macroscopic MA strings prepared from various metal chlorides solution, as determined by electronic microscopy, X-ray diffraction, and actuation speed measurements, is presented. Macroscopic MA strings prepared from calcium and magnesium ions provide a high degree of alignment and fast response photoactuation. By the selection of metal ions and chain length of MAs, the macroscopic MA string structure and function can be controlled, demonstrating the potential of generating multiple photoresponsive supramolecular systems from an identical molecular structure.

Artificial muscle-like function from hierarchical supramolecular assembly of photoresponsive molecular motors.

A striking feature of living systems is their ability to produce motility by amplification of collective molecular motion from the nanoscale up to macroscopic dimensions. Some of nature's protein motors, such as myosin in muscle tissue, consist of a hierarchical supramolecular assembly of very large proteins, in which mechanical stress induces a coordinated movement. However, artificial molecular muscles have often relied on covalent polymer-based actuators. Here, we describe the macroscopic contractile muscle-like motion of a supramolecular system (comprising 95% water) formed by the hierarchical self-assembly of a photoresponsive amphiphilic molecular motor. The molecular motor first assembles into nanofibres, which further assemble into aligned bundles that make up centimetre-long strings. Irradiation induces rotary motion of the molecular motors, and propagation and accumulation of this motion lead to contraction of the fibres towards the light source. This system supports large-amplitude motion, fast response, precise control over shape, as well as weight-lifting experiments in water and air.

Synthesis and Catalytic Applications of a Triptycene-Based Monophosphine Ligand for Palladium-Mediated Organic Transformations.

1-Methoxy-8-(diphenylphosphino)triptycene (1), featuring high structural rigidity and steric bulkiness around the phosphine functionality, was synthesized as a new chiral monophosphine ligand for transition metal-catalyzed reactions. In the presence of 5-10 mol ppm (i.e., 0.0005-0.001 mol %) Pd(OAc)2 and 1 (2 equiv for Pd), Suzuki-Miyaura cross-coupling reactions of aryl bromides and arylboronic acids proceeded effectively under mild atmospheric conditions to give the corresponding biaryl compounds in a high yield. The single-crystal X-ray analysis of a Pd(II) complex of 1 revealed its coordination structure, in which two homochiral molecules form a dimer, suggesting that triptycene could provide a chiral environment for asymmetric organic transformations. In fact, optically active 1 obtained by optical resolution showed good enantioselectivity in the palladium-catalyzed asymmetric hydrosilylation of styrene, which represents, for the first time, the asymmetric catalytic activity of triptycene-based monophosphine ligands.

Supramolecular Scaffold for Tailoring the Two-Dimensional Assembly of Functional Molecular Units into Organic Thin Films.

Tailoring structurally anisotropic molecular assemblies while controlling their orientation on solid substrates is an important subject for advanced technologies that use organic thin films. Here we report a supramolecular scaffold based on tripodal triptycene assemblies, which enables functional molecular units to assemble into a highly oriented, multilayered two-dimensional (2D) structure on solid substrates. The triptycene building block carries an ethynyl group and three flexible side chains at the 10- and 1,8,13-positions, respectively. These bridgehead-substituted tripodal triptycenes self-assembled on solid substrates to form a well-defined "2D hexagonal + 1D lamellar" structure, which developed parallel to the surface of the substrates. Remarkably, the assembling properties of the triptycene building blocks, particularly for a derivative with tri(oxyethylene)-containing side chains, were not impaired when the alkyne terminal was functionalized with a large molecular unit such as C60, which is comparable in diameter to the triptycene framework. Consequently, thin films with a multilayered 2D assembly of the C60 unit were obtained. Flash-photolysis time-resolved microwave conductivity (FP-TRMC) measurements revealed that the C60 film exhibits highly anisotropic charge-transport properties. Bridgehead-substituted tripodal triptycenes may provide a versatile supramolecular scaffold for tailoring the 2D assembly of molecular units into a highly oriented thin film, and in turn for exploiting the full potential of anisotropic molecular functions.