Molecular self-assembly is the spontaneous association of molecules under equilibrium conditions into stable, structurally well-defined aggregates joined by noncovalent bonds. Molecular self-assembly is ubiquitous in biological systems and underlies the formation of a wide variety of complex biological structures. Understanding self-assembly and the associated noncovalent interactions that connect complementary interacting molecular surfaces in biological aggregates is a central concern in structural biochemistry. Self-assembly is also emerging as a new strategy in chemical synthesis, with the potential of generating nonbiological structures with dimensions of 1 to 10(2) nanometers (with molecular weights of 10(4) to 10(10) daltons). Structures in the upper part of this range of sizes are presently inaccessible through chemical synthesis, and the ability to prepare them would open a route to structures comparable in size (and perhaps complementary in function) to those that can be prepared by microlithography and other techniques of microfabrication.

Molecular self-assembly and nanochemistry: A chemical strategy for the synthesis of nanostructures

The widespread use of controlled molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform specific tasks. This is a scientific area of great contemporary interest and extraordinary recent growth, yet the notion of molecular-level machines dates back to a time when the ideas surrounding the statistical nature of matter and the laws of thermodynamics were first being formulated. Here we outline the exciting successes in taming molecular-level movement thus far, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion. We also highlight some of the issues and challenges that still need to be overcome.

Synthetic molecular motors and mechanical machines.

23 Stereocontrol of Lactide ROP 6164 231 Isotactic Polylactides 6164 232 Syndiotactic Polylactides 6166 233 Heterotactic Polylactides 6166 3 Anionic Polymerization 6166 4 Nucleophilic Polymerization 6168 41 Mechanistic Considerations 6168 42 Catalysts 6169 421 Enzymes 6169 422 Organocatalysts 6169 43 Stereocontrol of Lactide ROP 6170 44 Depolymerization 6170 5 Cationic Polymerization 6170 6 Conclusion and Perspectives 6171 7 Acknowledgments 6173 8 References and Notes 6173

Controlled ring-opening polymerization of lactide and glycolide.

BACKGROUND Hydrogels are formed through the cross-linking of hydrophilic polymer chains within an aqueous microenvironment. The gelation can be achieved through a variety of mechanisms, spanning physical entanglement of polymer chains, electrostatic interactions, and covalent chemical cross-linking. The water-rich nature of hydrogels makes them broadly applicable to many areas, including tissue engineering, drug delivery, soft electronics, and actuators. Conventional hydrogels usually possess limited mechanical strength and are prone to permanent breakage. The lack of desired dynamic cues and structural complexity within the hydrogels has further limited their functions. Broadened applications of hydrogels, however, require advanced engineering of parameters such as mechanics and spatiotemporal presentation of active or bioactive moieties, as well as manipulation of multiscale shape, structure, and architecture. ADVANCES Hydrogels with substantially improved physicochemical properties have been enabled by rational design at the molecular level and control over multiscale architecture. For example, formulations that combine permanent polymer networks with reversibly bonding chains for energy dissipation show strong toughness and stretchability. Similar strategies may also substantially enhance the bonding affinity of hydrogels at interfaces with solids by covalently anchoring the polymer networks of tough hydrogels onto solid surfaces. Shear-thinning hydrogels that feature reversible bonds impart a fluidic nature upon application of shear forces and return back to their gel states once the forces are released. Self-healing hydrogels based on nanomaterial hybridization, electrostatic interactions, and slide-ring configurations exhibit excellent abilities in spontaneously healing themselves after damages. Additionally, harnessing techniques that can dynamically and precisely configure hydrogels have resulted in flexibility to regulate their architecture, activity, and functionality. Dynamic modulations of polymer chain physics and chemistry can lead to temporal alteration of hydrogel structures in a programmed manner. Three-dimensional printing enables architectural control of hydrogels at high precision, with a potential to further integrate elements that enable change of hydrogel configurations along prescribed paths. OUTLOOK We envision the continuation of innovation in new bioorthogonal chemistries for making hydrogels, enabling their fabrication in the presence of biological species without impairing cellular or biomolecule functions. We also foresee opportunities in the further development of more sophisticated fabrication methods that allow better-controlled hydrogel architecture across multiple length scales. In addition, technologies that precisely regulate the physicochemical properties of hydrogels in spatiotemporally controlled manners are crucial in controlling their dynamics, such as degradation and dynamic presentation of biomolecules. We believe that the fabrication of hydrogels should be coupled with end applications in a feedback loop in order to achieve optimal designs through iterations. In the end, it is the combination of multiscale constituents and complementary strategies that will enable new applications of this important class of materials.

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Advances in engineering hydrogels

Hydrogels attract great attention as biomaterials as a result of their soft and wet nature, similar to that of biological tissues. Recent inventions of several tough hydrogels show their potential as structural biomaterials, such as cartilage. Any given application, however, requires a combination of mechanical properties including stiffness, strength, toughness, damping, fatigue resistance and self-healing, along with biocompatibility. This combination is rarely realized. Here, we report that polyampholytes, polymers bearing randomly dispersed cationic and anionic repeat groups, form tough and viscoelastic hydrogels with multiple mechanical properties. The randomness makes ionic bonds of a wide distribution of strength. The strong bonds serve as permanent crosslinks, imparting elasticity, whereas the weak bonds reversibly break and re-form, dissipating energy. These physical hydrogels of supramolecular structure can be tuned to change multiple mechanical properties over wide ranges by using diverse ionic combinations. This polyampholyte approach is synthetically simple and dramatically increases the choice of tough hydrogels for applications.

https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/56662/1/Gong-Manuscript-1.pdf

Physical hydrogels composed of polyampholytes demonstrate high toughness and viscoelasticity

A photoresponsive polymeric material, in which [2]rotaxane units with α-cyclodextrin threading onto an azobenzene derivative is used as a topological cross-link for the main chains of the polymeric...

A Photoresponsive Polymeric Actuator Topologically Cross-Linked by Movable Units Based on a [2]Rotaxane

A molecular shuttle is a prototype of molecular machines capable of shuttling a part back and forth in the molecule. To control the shuttling of a macrocycle, we studied the reeling of an axis molecule into a macrocyclic host molecule located at the end of the axis. [2]Rotaxane and [3]rotaxane are composed of α-cyclodextrin (α-CD) rotors, a decamethylene chain, and a stilbene unit as axes and an altro-α-CD stopper containing one altropyranose unit and five glucopyranose units. The α-CD rotor of [2]rotaxane includes the decamethylene chain in DMSO-d6 and moves to include the stilbene group in D2O. It should be noted that the altro-α-CD stopper group reorients to include the decamethylene chain in D2O. The mechanism for tumbling was elucidated with 2D ROESY NMR measurements and kinetic studies. These studies showed that an altropyranose unit of the altro-α-CD stopper tumbles to form a self-inclusion complex in aqueous solution. The altro-α-CD stopper of [2]rotaxane reels an axis molecule into its cavity and...

A Molecular Reel: Shuttling of a Rotor by Tumbling of a Macrocycle

The interaction of polyacrylamide(pAAm)-based gel modified with benzyl (Bz) moiety (Bz(x)-gel, where x denotes the mol % content of Bz moiety) with a pAAm-based gel possessing cyclodextrin (CD) moieties (αCD-gel, βCD-gel, and γCD-gel) was investigated at various temperatures to elucidate the effect of temperature on the formation of macroscopic assembly. The interaction of Bz(x)-gel with CD-gels was stronger at a lower temperature, consistent with the binding constants for the model system of pAAm modified with 1 mol % Bz moiety and native CDs. Bz(15)-gel interacted only with βCD-gel at a higher temperature (<ca. 90 °C), with αCD-gel at a temperature ≤15 °C, and with γCD-gel at 5 °C to form gel assemblies. The formation of gel assemblies depending on temperature showed a good reversibility. On the basis of these observations, it is concluded that temperature is also an important stimulus for macroscopic assembly based on molecular recognition.

Temperature-Sensitive Macroscopic Assembly Based on Molecular Recognition

A methodology for preparing supramolecular hydrogels from guest-modified cyclodextrins (CDs) based on the host-guest and hydrogen-bonding interactions of CDs is presented. Four types of modified CDs were synthesized to understand better the gelation mechanism. The 2D ROESY NMR spectrum of beta-CD-AmTNB (Am=amino, TNB=trinitrobenzene) reveals that the TNB group was included in the beta-CD cavity. Pulsed field gradient NMR (PFG NMR) spectroscopy and AFM show that beta-CD-AmTNB formed a supramolecular polymer in aqueous solution through head-to-tail stacking. Although beta-CD-AmTNB did not produce a hydrogel due to insufficient growth of supramolecular polymers, beta-CD-CiAmTNB (Ci=cinnamoyl) formed supramolecular fibrils through host-guest interactions. Hydrogen bonds between the cross-linked fibrils resulted in the hydrogel, which displayed excellent chemical-responsive properties. Gel-to-sol transitions occurred by adding 1-adamantane carboxylic acid (AdCA) or urea. (1)H NMR and induced circular dichroism (ICD) spectra reveal that AdCA released the guest parts from the CD cavity and that urea acts as a denaturing agent to break the hydrogen bonds between CDs. The hydrogel was also destroyed by adding beta-CD, which acts as the competitive host to reduce the fibrils. Furthermore, the gel changed to a sol by adding methyl orange (MO) as a guest compound, but the gel reappeared upon addition of alpha-CD, which is a stronger host for MO.

Construction of chemical-responsive supramolecular hydrogels from guest-modified cyclodextrins.

Metal-ligand interactions with various proteins form in vivo metal assemblies. In recent years, metallosupramolecular approaches have been utilized to forge an assortment of fascinating two- and three-dimensional nano-architectures and macroscopic materials, such as metal-ligand coordination polymeric materials, have promise in artificial systems. However to the best of our knowledge, the self-assembly of macroscopic materials through metal-ligand interactions has yet to be reported. Herein we demonstrate a gel assembly formed via metal-ligand interactions using polyacrylamide modified with Fe-porphyrin and L-histidine moieties. The stress values for the assembly increase as the concentration of Fe-porphyrin or L-histidine in the gels increases. Moreover, agitation of Fe-porphyrin gel, Zn-porphyrin gel and L-histidine gel in an 80 mM Tris-acetate buffer (pH 9.0) results in selective adhesion of the Fe-porphyrin gel to the L-histidine gel based on the affinities of Fe-porphyrin and Zn-porphyrin with L-histidine.

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Yoshinori Takashima

Papers

A Photoresponsive Polymeric Actuator Topologically Cross-Linked by Movable Units Based on a [2]Rotaxane

A Molecular Reel: Shuttling of a Rotor by Tumbling of a Macrocycle

Temperature-Sensitive Macroscopic Assembly Based on Molecular Recognition

Construction of chemical-responsive supramolecular hydrogels from guest-modified cyclodextrins.

Reversible self-assembly of gels through metal-ligand interactions