Giant molecules:where chemistry,physics,and bio-science meet

This feature article focuses on the recent development of giant molecules,which has emerged at the interface among chemistry,physics,and bio-science.Their molecular designs are inspired by natural polymers like proteins and are modularly constructed from molecular nanoparticle building blocks via sequential "click" chemistry.Most important molecular parameters such as topology,composition,and molecular weight can be precisely controlled.Their hierarchical assembly reveals many features reminiscent of both small molecules and proteins yet unusual for conventional synthetic polymers.These features are summarized and compared along with synthetic polymers and proteins.Specifically,examples are given in each category of giant molecules to illustrate the characteristics of their hierarchical assembly across different length,time and energy scales.The idea of "artificial domain" is presented in analogy to the structural domains in proteins.By doing so,we aim to develop a rational and modular approach toward functional materials.The factors that dominate the materials functions are discussed with respect to the precision and dynamics of the assembly.The complexity of structure-function relationship is acknowledged,which suggests that there is still a long way to go toward the convergence of synthetic polymers and biopolymers.     

A survey of tellurium-centered secondary-bonding supramolecular synthons

The crystal structures of tellurium compounds frequently display intermolecular contacts between the chalcogen and atoms possessing lone pairs of electrons. Analysis of the data deposited in the Cambridge crystallographic database shows that the shortest secondary bonding interactions (SBIs) are formed when oxygen, nitrogen or chlorine are the donor atoms for SBIs. In addition, these SBIs are shortest when they occur opposite to a bond between tellurium and oxygen, nitrogen, fluorine, chlorine or the nitrile functional group. The structural motifs assembled in these systems fall within eight general categories, from single to multiple bonded supramolecular synthons. The use of multiple points of attachment between molecules leads, in principle, to stronger and more directional supramolecular synthons. The overall structures assembled by the most important tellurium-based supramolecular synthons and prospects for their application in crystal engineering are discussed.     

Functional Material Systems Based on Soft Cages

Discrete molecular soft cages integrate multiple functionalities in one molecule. They express their functions from the confined space in their cavity, functional groups in the cavity interior wall and exterior wall, and the chelating nodes in many chelating cages. Such functional integrity render cage molecules special applications in material engineering. Increasing applications of cage molecules in material design have been reported in recent years. Compared with other cavity-rich molecular structures such as metal-organic framework (MOF) or covalent organic frameworks (COF), discrete soft cages present the unique advantage of material design flexibility, that they can easily composite with nanoparticles or polymers and exist in materials of various forms. We document the development of cage-based materials in recent years and expect to further inspire materials engineering to integrate contribution from the functionality specificity of cage molecules and ultimately promote the development of functional materials and thus human life qualities.     

Recurrence of carboxylic acid-pyridine supramolecular synthon in the crystal structures of some pyrazinecarboxylic acids.

X-ray crystal structures of pyrazinic acid 1 and isomeric methylpyrazine carboxylic acids 2-4 are analyzed to examine the occurrence of carboxylic acid-pyridine supramolecular synthon V in these heterocyclic acids. Synthon V, assembled by (carboxyl)O-H...N(pyridine) and (pyridine)C-H...O(carbonyl) hydrogen bonds, controls self-assembly in the crystal structures of pyridine and pyrazine monocarboxylic acids. The recurrence of acid-pyridine heterodimer V compared to the more common acid-acid homodimer I in the crystal structures of pyridine and pyrazine monocarboxylic acids is explained by energy computations in the RHF 6-31G* basis set. Both the O-H.N and the C-H...O hydrogen bonds in synthon V result from activated acidic donor and basic acceptor atoms in 1-4. Pyrazine 2,3- and 2,5-dicarboxylic acids 10 and 11 crystallize as dihydrates with a (carboxyl)O-H...O(water) hydrogen bond in synthon VII, a recurring pattern in the diacid structures. In summary, the carboxylic acid group forms an O-H...N hydrogen bond in pyrazine monocarboxylic acids and an O-H...O hydrogen bond in pyrazine dicarboxylic acids. This structural analysis correlates molecular features with supramolecular synthons in pyridine and pyrazine carboxylic acids for future crystal engineering strategies.     

Crystal structure prediction of aminols: advantages of a supramolecular synthon approach with experimental structures

The supramolecular synthon approach to crystal structure prediction (CSP) takes into account the complexities inherent in crystallization. The synthon is a kinetically favored unit, and through analysis of commonly occurring synthons in a group of related compounds, kinetic factors are implicitly invoked. The working assumption is that while the experimental structure need not be at the global minimum, it will appear somewhere in a list of computationally generated structures so that it can be suitably identified and ranked upward using synthon information. These ideas are illustrated with a set of aminophenols, or aminols. In the first stage, a training database is created of the 10 isomeric methylaminophenols. The crystal structures of these compounds were determined. The prototypes 2-, 3-, and 4-aminophenols were also included in the training database. Small and large synthons in these 13 crystal structures were then identified. Small synthons are of high topological but low geometrical value and are used in negative screens to eliminate computationally derived structures that are chemically unreasonable. Large synthons are more restrictive geometrically and are used in positive screens ranking upward predicted structures that contain these more well-defined patterns. In the second stage, these screens are applied to CSP of nine new aminols carried out in 14 space groups. In each space group, up to 10 lowest energy structures were analyzed with respect to their synthon content. The results are encouraging, and the predictions were classified as good, unclear, or bad. Two predictions were verified with actual crystal structure determinations.     

Co-crystallization of glycine anhydride with the hydroxybenzoic acids: Controlled formation of dimers via synthons cooperation and structural characterization

The results of crystallographic analyses on 1:1 and 1:4 well-defined co-crystals formed between glycine anhydride and each of 4-hydroxybenzoic acid and 3,5-dihydroxybenzoic acid are described. Neutral molecules are connected via heteromeric O-H···O and N-H···O contacts leading to different packing arrangements of supramolecular chains. On the basis of the molecular structures of glycine anhydride and carboxylic acid guests, the hydrogen bonds are arranged to give centrosymmetric synthons V and VII which are noteworthy for their robustness. Hydrogen-bond interactions between glycine anhydride and aromatic acid provide sufficient driving force to direct molecular recognition and crystal packing. Utilization of the orientation of functional groups of the building blocks, the acidity, and weak interactions provides a route for the creation of novel supra- molecular architectures in the crystal lattice. Both two co-crystals contain the expected hydrogen-bonded motifs, and there has been no proton transfer from either of the two carboxylic acids to the aza compound moiety. This demonstrates that glycine anhydride is very capable of affecting the construction of binary co-crystals in a predictable and rationale manner. It is noted that synthons VⅢ and IX are fairly large, but the real challenge in crystal engineering is to find a big enough synthon that occurs often enough. Thermal stability of these compounds has been investigated by thermogravimetric analysis (TGA) of mass loss.     

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.     

Graph theory of synthons

A graph-theory model of synthons is suggested. A synthon is a special kind of the molecular graph in which some vertices are distinguished from other ones, and they are called the virtual vertices. The most important property of the synthons is that the constraint of strict stoichiometry is removed and the virtual vertices formally correspond to functional groups that are not closely specified.     

Order from disorder: Directed assembly of alkyl-π functional molecular liquids

Controlled self-assembly of π-conjugated molecules is a widely accepted approach to optimizing the performance of organic optoelectronics. In particular, directed assembly delivers precisely organized π-conjugated units in response to external stimuli. The attachment of branched alkyl chains not only modulates these assembly processes, but also isolates the π-core as observed in alkyl-π functional molecular liquids (FMLs). This review highlights recent advances in alkyl-π FMLs, their molecular design principle, and the methodologies to achieve their directed assembly by chemical additives and physical stimuli. It also presents how the disorder-to-order transition in alkyl-π FMLs leads to altered photoluminescence and other inherent benefits of these stimuli-driven assembled structures, which comprise a new paradigm in the field of stimuli-responsive soft materials and their application in soft electronics.     

Functional Liquid‐Crystalline Assemblies: Self‐Organized Soft Materials

In the 21st century, soft materials will become more important as functional materials because of their dynamic nature. Although soft materials are not as highly durable as hard materials, such as metals, ceramics, and engineering plastics, they can respond well to stimuli and the environment. The introduction of order into soft materials induces new dynamic functions. Liquid crystals are ordered soft materials consisting of self‐organized molecules and can potentially be used as new functional materials for electron, ion, or molecular transporting, sensory, catalytic, optical, and bio‐active materials. For this functionalization, unconventional materials design is required. Herein, we describe new approaches to the functionalization of liquid crystals and show how the design of liquid crystals formed by supramolecular assembly and nano‐segregation leads to the formation of a variety of new self‐organized functional materials.     

Co-assembly of Patchy Polymeric Micelles and Protein Molecules

The development in the synthesis and self-assembly of patchy nanoparticles has resulted in the creation of complex hierarchical structures. Co-assembly of polymeric nanoparticles and protein molecules combines the advantages of polymeric materials and biomolecules, and will produce new functional materials. Co-assembly of positively charged patchy micelles and negatively charged bovine serum albumin (BSA) molecules is investigated. The patchy micelles, which were synthesized using block copolymer brushes as templates, leads to co-assembly with protein molecules into vesicular structures. The average size of the assembled structures can be controlled by the molar ratio of BSA to patchy micelles. The assembled structures are dissociated in the presence of trypsin. The protein–polymer hybrid vesicles could find potential applications in medicine.     

Functional liquid-crystalline assemblies: self-organized soft materials

In the 21st century, soft materials will become more important as functional materials because of their dynamic nature. Although soft materials are not as highly durable as hard materials, such as metals, ceramics, and engineering plastics, they can respond well to stimuli and the environment. The introduction of order into soft materials induces new dynamic functions. Liquid crystals are ordered soft materials consisting of self-organized molecules and can potentially be used as new functional materials for electron, ion, or molecular transporting, sensory, catalytic, optical, and bio-active materials. For this functionalization, unconventional materials design is required. Herein, we describe new approaches to the functionalization of liquid crystals and show how the design of liquid crystals formed by supramolecular assembly and nano-segregation leads to the formation of a variety of new self-organized functional materials.     

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.     

Dynamic covalent gels assembled from small molecules: from discrete gelators to dynamic covalent polymers

Dynamic covalent chemistry has emerged recently to be a powerful tool to construct functional materials. This article reviews the progress in the research and development of dynamic covalent chemistry in gels assembled from small molecules. First dynamic covalent reactions used in gels are reviewed to understand the dynamic covalent bonding. Afterwards the catalogues of dynamic covalent gels are reviewed according to the nature of gelators and the interactions between gelators. Dynamic covalent bonding can be involved to form low molecular weight gelators. Low molecular weight molecules with multiple functional groups react to form dynamic covalent cross-linked polymers and act as gelators. Two catalogues of gels show different properties arising from their different structures. This review aims to illustrate the structure-property relationships of these dynamic covalent gels.     

Co‐assembly of Patchy Polymeric Micelles and Protein Molecules

The development in the synthesis and self‐assembly of patchy nanoparticles has resulted in the creation of complex hierarchical structures. Co‐assembly of polymeric nanoparticles and protein molecules combines the advantages of polymeric materials and biomolecules, and will produce new functional materials. Co‐assembly of positively charged patchy micelles and negatively charged bovine serum albumin (BSA) molecules is investigated. The patchy micelles, which were synthesized using block copolymer brushes as templates, leads to co‐assembly with protein molecules into vesicular structures. The average size of the assembled structures can be controlled by the molar ratio of BSA to patchy micelles. The assembled structures are dissociated in the presence of trypsin. The protein–polymer hybrid vesicles could find potential applications in medicine.     

Discovery of Structural Complexity through Self-Assembly of Molecules Containing Rodlike Components

Hierarchical structures are important for transferring and amplifying molecular functions to macroscopic properties of materials. In this regard, rodlike molecules have emerged as one of the most promising molecular building blocks to construct functional materials. Although the self-assembly of conventional molecules containing rodlike components generally results in nematic or layered smectic phases, due to the preferred parallel arrangements of rodlike components, extensive efforts have revealed that rational molecular design provides a versatile platform to engineer rich self-assembled structures. Herein, first successes achieved in polyphilic liquid crystals and rod–coil block systems are summarized. Special attention is paid to recent progress in the conjugation of rodlike building blocks with other molecular building blocks through the molecular Lego approach. Rod-based giant surfactants, sphere–rod conjugates, and dendritic rodlike molecules are covered. Future perspectives of the self-assembly of molecules containing rodlike components are also provided.     

Crystal engineering: a holistic view

Crystal engineering, the design of molecular solids, is the synthesis of functional solid-state structures from neutral or ionic building blocks, using intermolecular interactions in the design strategy. Hydrogen bonds, coordination bonds, and other less directed interactions define substructural patterns, referred to in the literature as supramolecular synthons and secondary building units. Crystal engineering has considerable overlap with supramolecular chemistry, X-ray crystallography, materials science, and solid-state chemistry and yet it is a distinct discipline in itself. The subject goes beyond the traditional divisions of organic, inorganic, and physical chemistry, and this makes for a very eclectic blend of ideas and techniques. The purpose of this Review is to highlight some current challenges in this rapidly evolving subject. Among the topics discussed are the nature of intermolecular interactions and their role in crystal design, the sometimes diverging perceptions of the geometrical and chemical models for a molecular crystal, the relationship of these models to polymorphism, knowledge-based computational prediction of crystal structures, and efforts at mapping the pathway of the crystallization reaction.     

Hydrogen‐Bonded Liquid Crystalline Materials: Supramolecular Polymeric Assembly and the Induction of Dynamic Function

Liquid crystals are molecular materials that combine anisotropy with dynamic nature. Recently, the use of hydrogen bonding for the design of functional liquid crystalline materials has been shown to be a versatile approach toward the control of simple molecularly assembled structures and the induction of dynamic function. A variety of hydrogen‐bonded liquid crystals has been prepared by molecular self‐assembly processes via hydrogen bond formation. Rod‐like and disk‐like low‐molecular weight complexes and polymers with side‐chain, main‐chain, network, and guest‐host structures have been built by the complexation of complimentary and identical hydrogen‐bonded molecules. These materials consist of closed‐type hydrogen bondings. Another type of hydrogen‐bonded liquid crystals consists of open‐type hydrogen bonding. In this case, the introduction of hydrogen bonding moieties, such as hydroxyl groups, induces microphase segregation leading to liquid crystalline molecular order. Moreover, liquid crystalline physical gels have been prepared by the molecular aggregation of hydrogen‐bonded molecules in non‐hydrogen‐bonded liquid crystals. They show significant electrooptical properties. An anisotropic gel is a new type of anisotropic materials forming heterogeneous structures.     

Synthetic Bilayer Membranes: Molecular Design,Self-Organization,and Application

Lipid bilayers are a most central building block of the biological molecular organization. Their two-dimensional self-assembly is essential to the generation of biological shapes and sizes on the molecular level. The observation that a totally synthetic amphiphile in water is spontaneously assembled to a bilayer structure suggested that bilayer formation is a general physicochemical phenomenon that is not restricted to particular structures of biolipid molecules. Bilayer formation is now observed for a large variety of synthetic amphiphiles which contain one, two, three, or four alkyl tails. The flexible alkyl tail may be replaced by perfluoroalkyl chains. The supramolecular structures obtained therefrom can be related to the component's molecular structure in many cases. The structural variety and the ease of molecular design make the synthetic bilayer an attractive vehicle for organizing covalently bound functional units and guest molecules. In addition, stable monolayers on water, planar lipid membranes (BLM), and free-standing cast films are obtainable because of the self-assembling property of bilayer-forming compounds. These molecular organizations display common supramolecular features. The use of the cast film as a molecular template provides exciting potential for the production of novel two-dimensional materials.     

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.